The risk profiles of pregnancy-related intracranial venous thrombosis: a retrospective study in a comprehensive hospital

The risk profiles of pregnancy-related intracranial venous thrombosis: a retrospective study in a comprehensive hospital | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The risk profiles of pregnancy-related intracranial venous thrombosis: a retrospective study in a comprehensive hospital Shaoying Wang, Ming Yao, Nan Hu, Juntao Liu, Bin Peng This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3852078/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objectives To investigate the risk factors and underlying causes of pregnancy-related intracranial venous thrombosis (PCVT). Methods A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. Results PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT ( P <0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one were diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.665C > T (p. Ala222Val). Conclusions The occur of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management. Intracranial venous thrombosis Pregnancy Risk factor Thrombophilia Antiphospholipid syndrome Introduction Intracranial venous thrombosis (CVT) is a special type of cerebrovascular disease that results from impaired blood flow or cerebrospinal fluid circulation, leading to intracranial hypertension and focal brain damage( 1 ). CVT affects female more than male, and women of reproductive ages are common victims( 2 ). Pregnancy has been identified as a risk factor for CVT and pregnancy-related CVT (PCVT) accounts for approximately 11–59% of CVT cases( 3 ). The nationwide CONCEPTION study shows that 24 per 100,000 pregnant women have a first stroke, and 17.4% of cases are CVT( 4 ). In China, the incidence of PCVT is about 202 per 100,000 pregnancies, and the mortality rate is 11.63%( 5 ), imposing a significant burden on pregnant women and their families. CVT is associated with several risk factors, which can be classified into transient and permanent ones.( 3 ) Among them, systematic diseases such as acquired thrombophilia like systemic lupus erythematosus (SLE) and hereditary thrombophilia have received increasing attention. However, most of the previous articles have been based on the overall CVT population. In addition, there is a misconception to attribute the cause of PCVT solely to pregnancy-induced hypercoagulability. Whether the same risk factors are established in pregnant women needs to be further investigated. Previous case reports or series show that anemia, obesity, smoking, cesarean section, epidural and spinal anesthesia during childbirth, pregnancy-induced hypertension, ovarian stimulation drugs, infections, Hyperhomocysteinemia (HHCY), antiphospholipid antibodies (aPL), and SLE may be closely associated with PCVT( 6 – 11 ). Several articles have described hereditary thrombophilia such as Factor V Leiden mutation (FVL), proteins C (PC) and protein S (PS), antithrombin III (ATIII) deficiency in PCVT( 11 – 21 ). However, these existing studies have not comprehensively analyzed the risk factors or etiology of PCVT, and the research is mainly conducted in European countries, India, and other countries, while there are a few studies in China which do not mention the acquired and genetic thrombophilia of PCVT, indicating a knowledge gap in this area( 22 – 25 ). For pregnant and puerperal women, early identification of risk factors associated to PCVT can reduce the incidence of PCVT. How do we identify women who are susceptible to PCVT, and what are the characteristics of these populations? On the other hand, what are the potential etiologic factors that should be a concern for women diagnosed with PCVT? Data in China is lacking. This study aims to investigate the risk factors of susceptible pregnant and postpartum women and the underlying causes of PCVT patients in a comprehensive hospital in China. Methods Study design and patient selection This was a single-center retrospective cohort study. We consecutively included patients who were diagnosed with CVT during pregnancy or within six weeks after delivery from January 2009 to December 2022 registered in Peking Union Medical College Hospital (PUMCH). In the study, CVT was diagnosed according to established criteria and confirmed by at least one of the following neuroradiological examinations: computed tomography venography (CTV), magnetic resonance imaging (MRI), magnetic resonance venography (MRV), or digital subtraction angiography (DSA)( 26 ). To explore the characteristics of pregnant and puerperal women susceptible to PCVT, we consecutively matched pregnant women in the first, second and third trimesters of pregnancy with matching gestational age in the obstetrics outpatient prenatal examination of our hospital, and hospitalized puerperium women without PCVT as controls in a 1:4 ratio. Women with these comorbidities were excluded from the selection of controls, including infertility or in vitro fertilization, pregnancy-induced hypertension or preeclampsia, underwent hormone therapy, had history of hemorrhage during labor or emergency delivery, malignancy, traumatic brain injuries, and incomplete data. The study was approved by the local hospital Ethics Committee (JS-2420). Written and informed consent was obtained from all participants. Data collection Demographic characteristics, medical history, clinical manifestations, and treatment for included patients were collected from the medical records. According to the current literature, the following laboratory results were intensively collected: routine blood count, coagulation, liver and kidney function, thrombophilia tests such as PC, PS, ATIII and activated PC resistance (APC-R), aPL such as anticardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aB2GPI), lupus anticoagulant (LA), and antinuclear antibodies, and homocysteine), imaging data (CT, MRI, MRV, DSA). Whole Exome Sequencing (WES) results were searched and summarized. Severity of illness at admission and discharge was assessed by Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS). Statistical analysis Characteristics were presented as mean (standard deviation) for continuous variables and frequency (%) for categorical variables. Differences between subjects with and without PCVT were compared using the Mann-Whitney U-test for continuous variables and the Chi-square test for categorical variables. Statistical significance was defined as two-tailed P <0.05, unless otherwise specified. All statistical analyses were performed using SPSS, version 23.0. Results From January 2009 to December 2022, we identified 311 hospitalized patients diagnosed with CVT. The patients included 183 females and 128 males, with a female-to-male ratio of approximately 1.5:1. Among the female patients, 130 were of childbearing age (15–45 years), and 16 had CVT during pregnancy or postpartum. Table 1 presented the demographic, clinical, and imaging characteristics of 16 CVT patients during pregnancy or postpartum. The average age was 29.06 ± 5.36 years. The majority of CVT events occurred in the first trimester (43.75%) and postpartum (37.5%). The most common symptom was headache (87.5%), followed by altered consciousness (50%), visual disturbances (50%), seizures (37.5%), and focal neurological deficits (37.5%). Tinnitus, cognitive impairment, and abnormal mental behavior were also be reported by included patients. Table 1 Demographic and clinical characteristics of total patients Characteristics Total Patients (n = 16) Demographics Age (mean ± SD) 29.06 ± 5.53 Phase, n (%) First trimester 7 (43.75) Second Trimester 1 (6.25) Third Trimester 0 puerperium 6 (37.5) Post-abortion 2 (12.5) Admission GCS score ≥ 9 13 <9 3 mRS at admission 0–2 4 3–5 12 6 0 Clinical characteristics, n (%) Headache 14 (87.5) Altered consciousness 8 (50) Seizure 6 (37.5) Visual impairment 8 (50) Focal neurological deficits 6 (37.5) cognitive impairment 3 (18.75) mental abnormality 1 (6.25) tinnitus 3 (18.75) Occluded sinus/vein, n (%) superior sagittal sinus 10 (62.5) Transvers sinus 11 (68.75) Sigmoid sinus 7 (43.75) Inferior sagittal sinus 1 (6.25) Cortical vein 3 (18.75) Deep system (Straight sinus/VG/ICV) 2 (12.5) Internal jugular vein 2 (12.5) More than one sinus 11 (68.75) Parenchymal lesion on imaging Hemorrhagic lesion 8/14 Non-hemorrhagic lesion (edema, infarction) 10/14 Anticoagulation treatment 15 (93.75) mRS at discharge 0–2 14 3–5 2 6 0 Abbreviation: SD, standard deviation; GCS, Glasgow coma scale; mRS, modified Rankin Scale; VG, vein of Galen; ICV, internal cerebral vein. Table 2 The risk factors of the study participants by pregnancy-related intracranial venous thrombosis Characteristics Pregnancy-related intracranial venous thrombosis Yes(n = 16) No(n = 64) P value Age ≥ 35 (y), n (%) 3 (18.8) 22 (34.4) 0.228 BMI > 30 (kg/m 2 ), n (%) 2 (14.3) 5 (7.8) 0.801 Ever smoking, n 0 0 First pregnancy/delivery, n (%) 6 (40) 31 (48.4) 0.556 History of adverse abortion, n (%) 2 (12.5) 3 (4.7) 0.260 History of CVT, n (%) 1 (6.3) 0 0.200 Pre-pregnancy anemia, n (%) 2 (12.5) 0 0.038 Pre-pregnancy diabetes, n (%) 0 1 (1.6) 1 PCOS, n 0 3 (4.7) 1 Gestational diabetes, n (%) 1 (6.3) 9 (14.1) 0.673 Dehydration, n (%) 2 (12.5) 0 0.038 Concurrent fever/Infection, n (%) 0 3 (4.7) 1 Oral contraceptive use, n 0 0 Ovarian stimulation drugs, n (%) 1 (6.3) 1 (1.6) 0.362 Anemia in pregnancy, n (%) 4 (25) 3 (4.7) 0.038 Thrombocytosis in pregnancy, n (%) 2 (12.5) 0 0.038 Thrombocytopenia in pregnancy, n (%) 5 (31.3) 0 <0.001 Fibrinogen (g/L), mean (SD) 3.94 (1.47) 3.75 (0.75) 0.927 Neutrophil (10 9 /L), mean (SD) 7.00 (3.33) 7.24 (2.44) 0.665 Lymphocyte (10 9 /L), mean (SD) 1.79 (0.53) 1.67 (0.51) 0.459 Platelet to lymphocyte ratio, mean (SD) 130.80 (98.73) 139.05 (46.32) 0.683 Neutrophil to lymphocyte ratio, mean (SD) 4.27 (2.47) 4.93 (2.70) 0.354 Platelet (10 9 /L) ×Neutrophil(10 9 /L) /Lymphocyte(10 9 /L), mean (SD) 834.70 (712.70) 1017.90 (529.82) 0.102 Abbreviation: SD, standard deviation; BMI, body mass index; PCOS, polycystic ovary syndrome; CVT, intracranial venous thrombosis. P value was for the test of difference between people with and without pregnancy-related intracranial venous thrombosis. Table 3 Characteristics of patients without Whole Exome Sequencing Age (y) Phage Pregnancy/childbirth history PMH BMI (kg/m 2 ) Platelet (10 9 /L) D-D (mg/L FEU) Thrombophilia aPL HCY (umol/L) Risk factors, etiology Pregnancy outcome 1 * 23 1st trimester (7th week) G2P0 Spontaneous abortion <30 34 765ug/L (0-420) PS: 37% (L) PC: 105% (N) ATIII: 84% (L)→100 (N) APC-R: ND ANA (-) aCL (-) aB2GPI (-) LA: N 9.7 Hereditary PS deficiency? Special type of APS? induced abortion 2 19 1st trimester (3rd month) G2P0 Healthy 26.16 249 3.28 PS: 80% (N) PC: 137% (N) ATIII: 88% (N) APC-R: ND ANA (-) aCL (-) aB2GPI (-) LA: N 14.9 / induced abortion 3 † 28 1st trimester (8th week) G1P0 Healthy 18.59 42 20.62 PS: 80% (N) PC: 106% (N) ATIII: 84% (N) APC-R: 13 (N) ANA (-) aCL (-) aB2GPI (-) LA: ND ND Thrombocytopenia; Dehydration induced abortion 4 34 2nd trimester (6th month) G3P1 IDA for 10yrs 30.49 229 2.08 PS: 43% (L)→88 (N) PC: 111% (N) ATIII: 71% (L)→91 (N) APC-R: 9.7 (N) ANA (-) aCL (-) aB2GPI (-) LA: N 42.9 IDA; HHCY; Dehydration; Obesity Cesarean section, stillbirth 5 35 1st trimester (6th week) G7P0 Recurrent miscarriage 27.54 65.7 NA NA ANA (+) aCL (-) aB2GPI (+) LA (+) NA APS induced abortion 6 34 Induced abortion (1 month) G2P1 Healthy 31.25 521 0.5 PS: 150% (N) PC: 122% (N) ATIII: 99 (N) APC-R: 3.5 (N) ANA (-) aCL (-) aB2GPI (-) LA: ND 6.1 Thrombocytosis Obesity 7 20 Puerperium; cesarean section (4th day) G1P1 Healthy <30 166 275ug/L (0-420) PS: 73% (N) PC: 129% (N) ATIII: 106% (N) APC-R: 8.4 (N) ANA (-) aCL (-) aB2GPI: ND LA: N ND / 8 24 1st trimester (8th week) G2P0 CVT, thrombocytopenia during last pregnancy 25.64 53 967ug/L (0-420) PS: 85% (N) PC: 181% (H) ATIII: 103% (N) APC-R: 7.9 (N) ANA (-) aCL (-) aB2GPI (-) LA: N 5.1 Thrombocytopenia induced abortion 9 ‡ 34 Puerperium; cesarean section (11st day) G1P1 Healthy NA 326 5.93 PS: (N) PC: (N) ATIII: (N) APC-R: (N) ND 7.5 History of using ovarian stimulation drugs 10 30 Spontaneous incomplete miscarriage (7th day) G2P1 Anemia for > 10yrs 21.48 24 20.69 PS: 50% (L) PC: 199% (H) ATIII: 74% (L) APC-R: 2.5 (N) ANA (-) aCL (-) aB2GPI (-) LA: N 11.3 SLE (Hematological, kidney, multiple serous fluid accumulation, hypoprotein) 11 § 34 1st trimester (6th week) G1P0 Healthy 18.18 550 NA PS: 45% (L) PC: 78% (N) ATIII: 86% (N) APC-R: 3(N) ANA (-) aCL (-) aB2GPI (-) LA: N 12.4 Essential thrombocythemia cesarean section; a healthy baby Abbreviation: PMH, past medical history; L, low; H, high; N, normal; ND, not detected; NA, not available; BMI, body mass index; D-D, D-dimer; aPL, antiphospholipid antibodies; HCY, homocysteine; PC, Protein C; PS, Protein S; ATIII, antithrombin III; APC-R, activated protein C resistance; ANA, anti-nuclear antibody; aCL, anticardiolipin; aB2GPI, anti-β2-glycoprotein I antibodies; LA, lupus anticoagulant; APS, antiphospholipid antibody syndrome; SLE, systemic lupus erythematosus; IDA, iron deficient anemia. * Platelet value was 46×10 9 /L, platelet surface associated antibody 429 (< 128), platelet value returned to normal after induced labor. † Hematology experts suggested follow-up for thrombocytopenia without treatment. Patient refused anticoagulation because of concerns about reduced platelet. ‡ Recurrent hand joint pain and morning stiffness during pregnancy. Patient requested transfer and did not complete APS related examinations. § JAK2 V617F was discovered during follow-up. Table 4. Characteristics of patients performed Whole Exome Sequencing Age (y) Phage Pregnancy childbirth history PMH BMI (kg/m 2 ) D-D Thrombophilia aPL HCY WES- Likely pathogenic WES- Uncertain significance Risk factors, etiology 1 35 Puerperium (7 th day) G1P1 Healthy 27.51 4.03 PS: 28% (L) PC: 125% (N) ATIII: 101% (N) APC-R: 2.8 (N) ANA (-) ACL (-) aB2GPI (-) LA: N 10.8 Heterozygous PROS1 c.301C>T (p. Arg101Cys) Heterozygous JAK2 c.2959G>A (p.Glu987Lys) Hereditary PS deficiency 2 * 25 Puerperium; Spontaneous labor (18 th day) G2P2 Healthy 22.76 2.39 PS: 12% (L) PC: 75% (N) ATIII: 111% (N) APC-R: 2.8 (N) ANA (-) ACL (-) aB2GPI (-) LA: 1.28(H) ND Heterozygous F8 c.144-1259C>T Heterozygous F8 c.6724G>A (p. Val2242Met) APS; Hereditary thrombophilia? 3 † 32 Puerperium; Spontaneous labor (5 th day) NA Healthy NA NA PS: N PC: N ATIII: N APC-R: N ANA (-) ACL (-) aB2GPI (±) LA: N 13.6 Homozygous MTHFR c.665C>T (p. Ala222Val) Heterozygous MMACHC c.609G>A (p. Trp203*) Heterozygous TMEM199 c.2T>C (p.0?) Heterozygous F13B c.986-15A>G APS? 4 32 Puerperium (7 th day) G1P1 Healthy 21.88 3.76 PS: 62% (L) PC: 98% (N) ATIII: 104% (N) APC-R: 3.2 (N) ANA (+) ACL (+) aB2GPI (+) LA: 1.32(H) 8.9 Homozygous MTHFR c.665C>T (p. Ala222Val) Heterozygous F13A1 c.1081G>A (p.Val361Met) APS 5 26 1 st trimester; induced abortion (11 th week) G2P1 Healthy 19.53 1.95 PS:58% (L)→78(N) PC:39%(L)→39%(L) ATIII: 102% (N) APC-R: 2.9 (N) ANA (-) ACL (-) aB2GPI (-) LA: N 10 Heterozygous PROC c.1218G>A (p. Met406Ile) Heterozygous F5 c.3331G>A (p.Ala1111Thr) Hereditary PC deficiency Abbreviation: PMH, past medical history; L, low; H, high; N, normal; ND, not detected; NA, not available; BMI, body mass index; D-D, D-dimer; aPL, antiphospholipid antibodies; HCY, homocysteine; PC, Protein C; PS, Protein S; ATIII, antithrombin III; APC-R, activated protein C resistance; ANA, anti-nuclear antibody; aCL, anticardiolipin; aB2GPI, anti-β2-glycoprotein I antibodies; LA, lupus anticoagulant. * Combined pulmonary embolism and inferior vena cava embolism; † High possibility of APS during follow-up Discussion CVT is a rare cerebral venous disorder, and pregnant and puerperium women are at increased risk. In the present study, we reported a small retrospective cohort of PCVT, exploring the risk factors and clinical predictors of PCVT and focusing on PCVT patients’ underlying causes. The characteristics of dehydration, pre-pregnancy anemia, and the presence of anemia, thrombocytopenia and thrombocytosis during pregnancy suggested a greater susceptibility to PCVT. For PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Nearly half of 16 patients had no pre-existing medical conditions before pregnancy, and PCVT could be the first manifestation of other diseases. Pregnant and postpartum women are a high-risk group for CVT. Extensive physiological, biochemical, and anatomical changes throughout normal pregnancy and puerperium result in hypercoagulability, hemodynamic alterations, and vascular damage (27) . Poor dietary intake, vomiting, excessive sweating, hypovolemia, and anemia could cause hemodynamic changes. Puerperal infections can induce vascular inflammation and systemic vasospasm (27, 28) . In our study, most patients developed CVT in the first trimester and postpartum period. The bimodal distribution phenomenon is reasonable (29) . Firstly, increased levels of vWF, fibrinogen, and factor VIII may trigger venous thrombosis in particularly susceptible women during early pregnancy. Previous reports suggested that women who have had CVT early on in their pregnancy tend to have another underlying mechanism for their hypercoagulable state such as aPL (30) . Secondly, postpartum-related conditions, such as dehydration, and prolonged bed rest might lead to the second peak of PCVT incidence. Previous studies have reported that anemia was associated with CVT (31) . Thrombocytosis, possibly a performance of myeloproliferative neoplasms such as essential thrombocythemia, and thrombocytopenia, possibly a manifestation of APS, were associated with CVT (32-34) . A cohort covering Pakistan, Turkey, and Mexico showed that anemia and dehydration were the commonest obstetric risk factors identified of PCVT (35) . In our study, except for anemia during pregnancy, history of pre-pregnancy anemia was also a significant risk factor for PCVT. However, to best of our knowledge, there was no study on the association of thrombocytosis during pregnancy and PCVT. We first proposed that thrombocytosis and thrombocytopenia during pregnancy were risk factors of PCVT and indicated a predisposition to PCVT. For pregnant and puerperal women without past medical history, anemia, thrombocytosis, and thrombocytopenia might be indicative of a higher risk of PCVT, even the warning of autoimmune diseases, myeloproliferative neoplasms, and other diseases (32-34) . It was necessary to pay more attention and further search for the causes, such as checking a specific aPL profile. Our study found that autoimmune disease such as APS, hereditary thrombophilia, and hematological disorders were common underlying causes of PCVT, different from the etiologic profiles years ago (6, 36) . The most common cause in the past was head or neck infections. Economic development, better control of infectious diseases, and a better understanding of the relationship between CVT and autoimmune diseases, hematological disorders and thrombophilia have contributed to this change. Autoimmune diseases, especially APS, might cause CVT. CVT is a rare complication of APS, with a reported incidence of 0.7%, and on the other hand, APS accounts for a large proportion of about 6-17% of CVT cases (34) . Autoimmune diseases were the most common cause, accounting for about 27.8% of CVT cases in women of childbearing age in a previous study at our hospital (37) . The neurologic damages caused by APS is related to immune mediated vascular, inflammatory, and direct neuronal effects. Small/microvascular thrombosis and the direct action of aPL, lead to the destruction of the blood-brain barrier, triggering leukocyte adhesion and complement activation, further leading to neurotoxicity of cytokines and antibodies (34) . In the present study, about 31% (5/16) of PCVT were diagnosed with APS. Among those five patients, three were completely healthy before pregnancy, and the other two patients had no other symptoms except for spontaneous abortion, suggesting that PCVT could be the first manifestation of APS. The diagnosis of APS is challenging and requires professional immunology experts to combine thrombotic events, adverse pregnancy outcomes, childbirth history, and aPL for a comprehensive evaluation. Besides, there was one patient with SLE who presented with PCVT as the initial manifestation. All patients received immunotherapy to control the primary disease. This highlights the importance of screening for autoimmune diseases in PCVT patients, which was essential for treatment and long-term management. Hereditary thrombophilia is an important etiology for CVT, accounting for approximately 34%-41% of cases in cohort studies (3) . The most common genetic risk factors for VTE in white individuals, such as FVL, prothrombin G20210A mutation, are rare in Asian populations, while PC, PS, and antithrombin deficiency are important for VTE in Asians (38) . PC may inactivate factors Va and VIIIa. Patients with homozygous or compound heterozygous subtypes may present with fulminant purpura in early life, while those with heterozygous subtypes may develop thromboembolism later in life. In our study, we identified one patient with severe PC deficiency, and WES revealed a heterozygous mutation in PROC gene (c.1218G>A, Met406Ile) (Table 4, patient 5). A previous study in Korea reported that Met406Ile was the second most common mutation in VTE patients and was absent in healthy controls (39) . Met406Ile has also been detected in a Chinese family with VTE (40) . The authors used homology modeling to demonstrate that the missense mutation (c.1218C>A, Met406lle) in PROC gene resulted in steric clashes and instability of PC structure, which could impair the normal physiological function of PC and cause hypercoagulability. In addition, 37.5% (6/16) of our patients showed reduced PS activity. Among them, three patients were considered to have gestational PS deficiency. Three patients had severe PS deficiency. One patient had a heterozygous mutation in PROS1 c.301C>T (p. Arg101Cys) (Table 4, patient 1). This mutation has been reported in a case of PS deficiency associated with a partial loss of APC cofactor activity (41) . Another patient with low PS activity did not have any PROS1 mutation but had a compound heterozygous mutation in the F8 gene (c.144-1259C>T; c.6724G>A (p. Val2242Met)) (Table 4, patient 2), which might cause X-linked thrombophilia due to factor VIII defect (42) . However, we did not perform functional testing to confirm this, which is a limitation and a goal for future research. We speculated that the low PS level may be a consequence of consumption due to the thrombotic process. One patient was suspected to have hereditary PS deficiency but did not undergo WES (Table 3, patient 1). There was no ATIII, FVL, or prothrombin G20210A mutation in our study. These results emphasized the importance of genetic testing for patients with suspected hereditary thrombophilia. In addition, homozygous MTHFR c.665C>T (p. Ala222Val) was considered a risk factor for CVT (43) . Hyperhomocysteinemia (HHCY) was reported to be associated with an increased risk of postpartum CVT (7) . However, there was no corresponding HHCY in our patients, which may be attributed to regular vitamin supplementation during pregnancy. Hematological disorders are also an important underlying cause of PCVT. JAK2 V617F could cause CVT (44) . In our study, we detected this mutation in a patient with essential thrombocythemia during follow-up (Table 1, patient 11), which suggested that genetic testing is necessary for patients with significant thrombocytosis. Although PCVT is a rare disease, it poses a serious threat to maternal and fetal health. If relevant risk factors could be identified during pregnancy in time, the occurrence of PCVT might be reduced. Hereditary thrombophilia and APS are very important etiologic factors; however, screening for thrombophilia, such as PS and PC activity, and a specific aPL profile was rarely performed during prenatal examinations, which illustrated a lack of understanding of PCVT. For pregnant and puerperium women with dehydration, pre-pregnancy anemia, or combined with anemia, thrombocytopenia, and thrombocytosis, who were more likely to suffer from PCVT, thrombophilia and a specific aPL profile are required, which needs to be further proved in multicenter cohorts. On the other hand, for confirmed PCVT, it is essential to perform an aggressive etiology screen. Primary disease control is necessary and the optimal duration of anticoagulants depended on the etiology. If CVT was secondary to transient and reversible risk factors, oral anticoagulants could be administered within three months. If the etiology was unknown or associated with a mild hereditary thrombosis, oral anticoagulants should continue for 6- 12 months. For those who suffered from more than two episodes of CVT or had a severe hereditary thrombophilia (e.g., Prothrombin G20210A homozygous, FVL homozygous, PC, PS, antithrombin deficiency, complex thrombophilia, APS), long-term anticoagulant therapy should be considered (26) . For PCVT patients detected no specified etiology, suspected of hereditary thrombophilia, and with significant thrombocytosis or thrombocytopenia, genetic testing may be necessary. Our study has several limitations that should be acknowledged. This is a retrospective study, and information bias and missing data are inevitable. In addition, the small number of patients limited the generalizability of our findings. Due to the limitation of the lack of thrombophilia and aPL data in controls, we failed to build a complete risk model that warrants further investigation in future studies with larger cohorts. Nevertheless, this study still provides valuable data for PCVT, especially in China. Conclusion In conclusion, this study emphasizes the necessity of recognizing susceptible pregnant and puerperal women with PCVT and the need for etiological screening. The occur of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. Autoimmune diseases, hereditary thrombophilia, and hematological disorders are common causes for confirmed PCVT patients. It is essential to screen for underlying causes for PCVT, especially hereditary or acquired thrombophilia, which could provide a more comprehensive insight and play a crucial role in long-term management. Declarations Ethics approval and consent to participate The authors state that all methods were carried out in accordance with relevant guidelines and regulations and followed the principles outlined in the Declaration of Helsinki for human. The study was approved by the Ethics Committee of Peking Union Medical College Hospital (JS-2420). Written and informed consent was obtained from all participants. Consent for publication Not applicable. Funding Capital Medical Development Research funding of China (No. 2020-1-4012). Acknowledgements Authors would like to thank all the authors of the original articles. Authors' information a Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. b Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China Availability of data and materials The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Peking Union Medical College Hospital. Author Contributions Shaoying Wang: study design, data collection, analysis, and interpretation, drafting of the manuscript; Ming Yao: data collection and interpretation; Nan Hu: contributed to data analysis; Juntao Liu: data collection; Bin Peng: study design, data collection, study supervision and manuscript revision. All authors have read and approved the manuscript. Conflict of Interest No conflict declared. References Bousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol. 2007;6(2):162–70. 10.1016/S1474-4422(07)70029-7 . Field TS, Hill MD. Cerebral Venous Thrombosis. Stroke. 2019;50(6):1598–604. 10.1161/STROKEAHA.119.025334 . Silvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555–65. 10.1038/nrneurol.2017.104 . Martin A, et al. Incidence and Time Trends of Pregnancy-Related Stroke Between 2010 and 2018: The Nationwide CONCEPTION Study. Neurology. 2022;99(15):e1598–608. 10.1212/WNL.0000000000200944 . Liang Z-W, Gao W-L, Feng L-M. Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium. Sci Rep. 2017;7:43866. 10.1038/srep43866 . Lanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke. 2000;31(6):1274–82. Nagaraja D, Noone ML, Bharatkumar VP, Christopher R. Homocysteine, folate and vitamin B(12) in puerperal cerebral venous thrombosis. J Neurol Sci. 2008;272(1–2):43–7. 10.1016/j.jns.2008.03.021 . Demir CF, et al. Clinical and radiological management and outcome of pregnancies complicated by cerebral venous thrombosis: a review of 19 cases. J Stroke Cerebrovasc Dis. 2013;22(8):1252–7. 10.1016/j.jstrokecerebrovasdis.2012.07.004 . Chambers DJ, Bhatia K, Columb M. Postpartum cerebral venous sinus thrombosis following obstetric neuraxial blockade: a literature review with analysis of 58 case reports. Int J Obstet Anesth. 2022;49:103218. 10.1016/j.ijoa.2021.103218 . Bajko Z, et al. Postpartum Cerebral Venous Thrombosis-A Single-Center Experience. Brain Sci. 2021;11(3). 10.3390/brainsci11030327 . Aaron S, et al. Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis. Neurol India. 2010;58(4):555–9. 10.4103/0028-3886.68676 . Dindagur N, Kruthika-Vinod TP, Christopher R. Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis. J Neurol Sci. 2006;249(1):25–30. Dindagur N, Kruthika-Vinod TP, Christopher R. Factor V gene A4070G mutation and the risk of cerebral veno-sinus thrombosis occurring during puerperium. Thromb Res. 2007;119(4):497–500. Sharpe CJ, Crowther MA, Webert KE, Donnery C. Cerebral venous thrombosis during pregnancy in the setting of type I antithrombin deficiency: case report and literature review. Transfus Med Rev. 2011;25(1):61–5. 10.1016/j.tmrv.2010.08.007 . Usui M, et al. Cerebral venous sinus thrombosis associated with protein S deficiency during pregnancy: a case report. J Obstet Gynaecol. 2020;40(1):135–6. 10.1080/01443615.2019.1606789 . Klai S, et al. Maternal cerebral venous thrombosis, uncommon but serious disorder, pathologic predictors and contribution of prothrombotic abnormalities. Blood Coagul Fibrinolysis. 2013;24(3):269–72. 10.1097/MBC.0b013e32835bace4 . Derex L, et al. Postpartum cerebral venous thrombosis, congenital protein C deficiency, and activated protein C resistance due to heterozygous factor V Leiden mutation. J Neurol Neurosurg Psychiatry. 1998;65(5):801–2. Jianu DC, et al. Diagnosis and Management of Mixed Transcortical Aphasia Due to Multiple Predisposing Factors, including Postpartum and Severe Inherited Thrombophilia, Affecting Multiple Cerebral Venous and Dural Sinus Thrombosis: Case Report and Literature Review. Diagnostics (Basel). 2021;11(8). 10.3390/diagnostics11081425 . Pleșa FC, et al. Challenges in Cerebral Venous Thrombosis Management-Case Reports and Short Literature Review. Life (Basel). 2023;13(2). 10.3390/life13020334 . Gazioglu S, Dinc G. Cerebral venous sinus thrombosis in pregnancy and puerperium. Acta Neurol Belg. 2021;121(4):967–72. 10.1007/s13760-020-01459-3 . Axelerad AD, et al. Case Reports of Pregnancy-Related Cerebral Venous Thrombosis in the Neurology Department of the Emergency Clinical Hospital in Constanta. Life (Basel). 2022;12(1). 10.3390/life12010090 . Jeng J-S, Tang S-C, Yip P-K. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis. 2004;18(4):290–5. Wang C, et al. Cerebral venous thrombosis as a rare cause of nausea and vomiting in early pregnancy: Case series in a single referral center and literature review. Front Neurol. 2022;13:912419. 10.3389/fneur.2022.912419 . Meng S-H, Li J-H, Zuo L-J, Feng L-M. The outcomes of pregnant and postpartum patients with cerebral venous sinus thrombosis after anticoagulant therapy. Med (Baltim). 2021;100(26):e26360. 10.1097/MD.0000000000026360 . Gao H, Yang B-J, Jin L-P, Jia X-F. Predisposing factors, diagnosis, treatment and prognosis of cerebral venous thrombosis during pregnancy and postpartum: a case-control study. Chin Med J (Engl). 2011;124(24):4198–204. Chinese Society of Neurology, Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of cerebral venous thrombosis 2019. Chin J Neurol. 2020;53(09):648–63. (in Chinese). Treadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J. 2008;84(991):238–45. 10.1136/pgmj.2007.066167 . Camargo EC, Singhal AB. Stroke in Pregnancy: A Multidisciplinary Approach. Obstet Gynecol Clin North Am. 2021;48(1):75–96. 10.1016/j.ogc.2020.11.004 . Cantu-Brito C, et al. Cerebrovascular complications during pregnancy and postpartum: clinical and prognosis observations in 240 Hispanic women. Eur J Neurol. 2011;18(6):819–25. 10.1111/j.1468-1331.2010.03259.x . Levine SR, et al. Cerebral venous thrombosis with lupus anticoagulants. Report of two cases. Stroke. 1987;18(4):801–4. Coutinho JM, et al. Association Between Anemia and Cerebral Venous Thrombosis: Case-Control Study. Stroke. 2015;46(10):2735–40. 10.1161/STROKEAHA.115.009843 . Gangat N, et al. Cerebral venous thrombosis and myeloproliferative neoplasms: A three-center study of 74 consecutive cases. Am J Hematol. 2021;96(12):1580–6. 10.1002/ajh.26336 . Chen W-B, Wang X-L. Cerebral Venous Sinus Thrombosis as the First Manifestation of JAK2V617F-positive Essential Thrombocythemia. Chin Med J (Engl). 2018;131(6):748–50. 10.4103/0366-6999.226903 . Leal Rato M, Bandeira M, Romão VC, Aguiar de Sousa D. Neurologic Manifestations of the Antiphospholipid Syndrome - an Update. Curr Neurol Neurosci. 2021;21(8):41. 10.1007/s11910-021-01124-z . Khan M, et al. Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis. Cerebrovasc Dis. 2023;52(4):393–400. 10.1159/000527155 . Qi X, Cui L-Y, Wang J-M. [Changes in clinical characteristics and treatment of cerebral venous and sinus thrombosis: analysis of 35 patients admitted in Peking Union Medical College Hospital]. Zhonghua Yi Xue Za Zhi. 2008;88(23):1624–6. Wu Y-T, et al. Clinical Features of CVT in Women and Effect on Subsequent Pregnancy: A Follow-Up Study in a Chinese National Comprehensive Hospital. J Stroke Cerebrovasc Dis. 2020;29(11):105274. 10.1016/j.jstrokecerebrovasdis.2020.105274 . Bounameaux H, Rosendaal FR. Venous thromboembolism: why does ethnicity matter? Circulation. 2011;123(20):2189–91. 10.1161/CIRCULATIONAHA.111.031690 . Kim H-J, et al. Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population. Haematologica. 2014;99(3):561–9. 10.3324/haematol.2013.092023 . Zhang L, et al. [Phenotypic detection and structure analysis of a PC missense mutation (Met406Ile) resulted in venous thromboembolism]. Zhonghua Yi Xue Za Zhi. 2013;93(29):2275–8. Franchi F, et al. c.301C > T (p.Arg101Cys): a novel mutation in the thrombin-sensitive region of protein S associated with a dysfunctional protein. Thromb Haemost. 2006;96(3):381–3. Simioni P, et al. Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia. Blood. 2021;137(17):2383–93. 10.1182/blood.2020008168 . Kalita J, Singh VK, Misra UK. A study of hyperhomocysteinemia in cerebral venous sinus thrombosis. Indian J Med Res. 2020;152(6):584–94. 10.4103/ijmr.IJMR_2125_18 . Orion D, et al. Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis. Front Neurol. 2022;13:783795. 10.3389/fneur.2022.783795 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 17 Jan, 2024 Submission checks completed at journal 17 Jan, 2024 Editor assigned by journal 17 Jan, 2024 First submitted to journal 10 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3852078","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267688201,"identity":"1855bdc7-46f6-4459-a3dc-bda246885ca4","order_by":0,"name":"Shaoying Wang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shaoying","middleName":"","lastName":"Wang","suffix":""},{"id":267688202,"identity":"6a175d00-48a5-470a-a04e-63f20e5d1321","order_by":1,"name":"Ming Yao","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Yao","suffix":""},{"id":267688203,"identity":"c462fb9c-8d6d-4ada-a8c8-4c909e38aa3b","order_by":2,"name":"Nan Hu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nan","middleName":"","lastName":"Hu","suffix":""},{"id":267688204,"identity":"c822f6e9-1dff-4493-a5ea-35d9a484dde2","order_by":3,"name":"Juntao Liu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Juntao","middleName":"","lastName":"Liu","suffix":""},{"id":267688205,"identity":"761ecf59-c90a-4866-a811-f1076dc769a2","order_by":4,"name":"Bin Peng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYJACZgYDBjt+CTBbQoZoLcmSMxgYG4BaeIjUwsDAuOEGWAsDYS3m7L2HXxcU3GE2vt18/NGNGgseBvbDRzfg02LZcy7NeobBMz6zO8cSm3OOAR3Gk5Z2A58Wgxs5ZsY8BoeZzW7kGDbnsAG1SPCY4ddy/w1YC+PmGSAt/4jRcoPH+DFIywYJoJbcNiK0WPbkmDHPMDicLHEjLXF2bp8EDxshv5iznzH+XPDnsB3/jOQDn3O+1cnxsx8+ht9hDAxsEigibPiUQ7UwfyCkaBSMglEwCkY4AAAmJUZR9ckdLQAAAABJRU5ErkJggg==","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"prefix":"","firstName":"Bin","middleName":"","lastName":"Peng","suffix":""}],"badges":[],"createdAt":"2024-01-11 02:59:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3852078/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3852078/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49811644,"identity":"af8eb393-9261-4e6f-89a7-5145c79d65e4","added_by":"auto","created_at":"2024-01-18 12:18:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":508312,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3852078/v1/43a834c4-b29f-4290-b797-e31a82278721.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The risk profiles of pregnancy-related intracranial venous thrombosis: a retrospective study in a comprehensive hospital","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIntracranial venous thrombosis (CVT) is a special type of cerebrovascular disease that results from impaired blood flow or cerebrospinal fluid circulation, leading to intracranial hypertension and focal brain damage(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). CVT affects female more than male, and women of reproductive ages are common victims(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Pregnancy has been identified as a risk factor for CVT and pregnancy-related CVT (PCVT) accounts for approximately 11\u0026ndash;59% of CVT cases(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The nationwide CONCEPTION study shows that 24 per 100,000 pregnant women have a first stroke, and 17.4% of cases are CVT(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In China, the incidence of PCVT is about 202 per 100,000 pregnancies, and the mortality rate is 11.63%(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), imposing a significant burden on pregnant women and their families.\u003c/p\u003e \u003cp\u003eCVT is associated with several risk factors, which can be classified into transient and permanent ones.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Among them, systematic diseases such as acquired thrombophilia like systemic lupus erythematosus (SLE) and hereditary thrombophilia have received increasing attention. However, most of the previous articles have been based on the overall CVT population. In addition, there is a misconception to attribute the cause of PCVT solely to pregnancy-induced hypercoagulability. Whether the same risk factors are established in pregnant women needs to be further investigated. Previous case reports or series show that anemia, obesity, smoking, cesarean section, epidural and spinal anesthesia during childbirth, pregnancy-induced hypertension, ovarian stimulation drugs, infections, Hyperhomocysteinemia (HHCY), antiphospholipid antibodies (aPL), and SLE may be closely associated with PCVT(\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Several articles have described hereditary thrombophilia such as Factor V Leiden mutation (FVL), proteins C (PC) and protein S (PS), antithrombin III (ATIII) deficiency in PCVT(\u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). However, these existing studies have not comprehensively analyzed the risk factors or etiology of PCVT, and the research is mainly conducted in European countries, India, and other countries, while there are a few studies in China which do not mention the acquired and genetic thrombophilia of PCVT, indicating a knowledge gap in this area(\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFor pregnant and puerperal women, early identification of risk factors associated to PCVT can reduce the incidence of PCVT. How do we identify women who are susceptible to PCVT, and what are the characteristics of these populations? On the other hand, what are the potential etiologic factors that should be a concern for women diagnosed with PCVT? Data in China is lacking. This study aims to investigate the risk factors of susceptible pregnant and postpartum women and the underlying causes of PCVT patients in a comprehensive hospital in China.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patient selection\u003c/h2\u003e \u003cp\u003eThis was a single-center retrospective cohort study. We consecutively included patients who were diagnosed with CVT during pregnancy or within six weeks after delivery from January 2009 to December 2022 registered in Peking Union Medical College Hospital (PUMCH). In the study, CVT was diagnosed according to established criteria and confirmed by at least one of the following neuroradiological examinations: computed tomography venography (CTV), magnetic resonance imaging (MRI), magnetic resonance venography (MRV), or digital subtraction angiography (DSA)(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). To explore the characteristics of pregnant and puerperal women susceptible to PCVT, we consecutively matched pregnant women in the first, second and third trimesters of pregnancy with matching gestational age in the obstetrics outpatient prenatal examination of our hospital, and hospitalized puerperium women without PCVT as controls in a 1:4 ratio. Women with these comorbidities were excluded from the selection of controls, including infertility or in vitro fertilization, pregnancy-induced hypertension or preeclampsia, underwent hormone therapy, had history of hemorrhage during labor or emergency delivery, malignancy, traumatic brain injuries, and incomplete data.\u003c/p\u003e \u003cp\u003e The study was approved by the local hospital Ethics Committee (JS-2420). Written and informed consent was obtained from all participants.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eDemographic characteristics, medical history, clinical manifestations, and treatment for included patients were collected from the medical records. According to the current literature, the following laboratory results were intensively collected: routine blood count, coagulation, liver and kidney function, thrombophilia tests such as PC, PS, ATIII and activated PC resistance (APC-R), aPL such as anticardiolipin antibodies (aCL), anti-β2-glycoprotein I antibodies (aB2GPI), lupus anticoagulant (LA), and antinuclear antibodies, and homocysteine), imaging data (CT, MRI, MRV, DSA). Whole Exome Sequencing (WES) results were searched and summarized. Severity of illness at admission and discharge was assessed by Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eCharacteristics were presented as mean (standard deviation) for continuous variables and frequency (%) for categorical variables. Differences between subjects with and without PCVT were compared using the Mann-Whitney U-test for continuous variables and the Chi-square test for categorical variables. Statistical significance was defined as two-tailed \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05, unless otherwise specified. All statistical analyses were performed using SPSS, version 23.0.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFrom January 2009 to December 2022, we identified 311 hospitalized patients diagnosed with CVT. The patients included 183 females and 128 males, with a female-to-male ratio of approximately 1.5:1. Among the female patients, 130 were of childbearing age (15\u0026ndash;45 years), and 16 had CVT during pregnancy or postpartum.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e presented the demographic, clinical, and imaging characteristics of 16 CVT patients during pregnancy or postpartum. The average age was 29.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.36 years. The majority of CVT events occurred in the first trimester (43.75%) and postpartum (37.5%). The most common symptom was headache (87.5%), followed by altered consciousness (50%), visual disturbances (50%), seizures (37.5%), and focal neurological deficits (37.5%). Tinnitus, cognitive impairment, and abnormal mental behavior were also be reported by included patients.\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic and clinical characteristics of total patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal Patients (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.06\u0026thinsp;\u0026plusmn;\u0026thinsp;5.53\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePhase, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst trimester\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (43.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSecond Trimester\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThird Trimester\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epuerperium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePost-abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdmission GCS score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emRS at admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eClinical characteristics, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (87.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAltered consciousness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSeizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVisual impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFocal neurological deficits\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecognitive impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emental abnormality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003etinnitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccluded sinus/vein, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esuperior sagittal sinus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTransvers sinus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (68.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSigmoid sinus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (43.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInferior sagittal sinus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCortical vein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDeep system (Straight sinus/VG/ICV)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInternal jugular vein\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMore than one sinus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11 (68.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eParenchymal lesion on imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemorrhagic lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-hemorrhagic lesion (edema, infarction)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10/14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnticoagulation treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (93.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emRS at discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u0026ndash;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eAbbreviation: SD, standard deviation; GCS, Glasgow coma scale; mRS, modified Rankin Scale; VG, vein of Galen; ICV, internal cerebral vein.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe risk factors of the study participants by pregnancy-related intracranial venous thrombosis\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003ePregnancy-related intracranial venous thrombosis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;35 (y), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (18.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22 (34.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026gt;\u0026thinsp;30 (kg/m\u003csup\u003e2\u003c/sup\u003e), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEver smoking, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst pregnancy/delivery, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (48.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.556\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistory of adverse abortion, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistory of CVT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-pregnancy anemia, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePre-pregnancy diabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCOS, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational diabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9 (14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.673\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDehydration, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConcurrent fever/Infection, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOral contraceptive use, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOvarian stimulation drugs, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.362\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnemia in pregnancy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytosis in pregnancy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytopenia in pregnancy, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFibrinogen (g/L), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.94 (1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.75 (0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophil (10\u003csup\u003e9\u003c/sup\u003e/L), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.00 (3.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.24 (2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLymphocyte (10\u003csup\u003e9\u003c/sup\u003e/L), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.79 (0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.67 (0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet to lymphocyte ratio, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130.80 (98.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e139.05 (46.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.683\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeutrophil to lymphocyte ratio, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.27 (2.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.93 (2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet (10\u003csup\u003e9\u003c/sup\u003e/L) \u0026times;Neutrophil(10\u003csup\u003e9\u003c/sup\u003e/L) /Lymphocyte(10\u003csup\u003e9\u003c/sup\u003e/L), mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e834.70 (712.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1017.90 (529.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eAbbreviation: SD, standard deviation; BMI, body mass index; PCOS, polycystic ovary syndrome; CVT, intracranial venous thrombosis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eP value was for the test of difference between people with and without pregnancy-related intracranial venous thrombosis.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCharacteristics of patients without Whole Exome Sequencing\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge (y)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePhage\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePregnancy/childbirth history\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePMH\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlatelet (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eD-D (mg/L FEU)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eThrombophilia\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eaPL\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHCY (umol/L)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRisk factors,\u003c/p\u003e\n \u003cp\u003eetiology\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePregnancy outcome\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(7th week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpontaneous abortion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e34\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e765ug/L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(0-420)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePS: 37% (L)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 105% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 84% (L)\u0026rarr;100 (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: ND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHereditary PS deficiency?\u003c/p\u003e\n \u003cp\u003eSpecial type of APS?\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(3rd month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.28\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 80% (N)\u003c/p\u003e\n \u003cp\u003ePC: 137% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 88% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: ND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(8th week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e42\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e20.62\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 80% (N)\u003c/p\u003e\n \u003cp\u003ePC: 106% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 84% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: 13 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: ND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytopenia;\u003c/p\u003e\n \u003cp\u003eDehydration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2nd trimester\u003c/p\u003e\n \u003cp\u003e(6th month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG3P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eIDA for 10yrs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e30.49\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e229\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.08\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 43% (L)\u0026rarr;88 (N)\u003c/p\u003e\n \u003cp\u003ePC: 111% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 71% (L)\u0026rarr;91 (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: 9.7 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e42.9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIDA;\u003c/p\u003e\n \u003cp\u003eHHCY;\u003c/p\u003e\n \u003cp\u003eDehydration;\u003c/p\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCesarean section, stillbirth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(6th week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG7P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eRecurrent miscarriage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e65.7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eANA (+)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eaB2GPI (+)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLA (+)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInduced abortion\u003c/p\u003e\n \u003cp\u003e(1 month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e31.25\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e521\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 150% (N)\u003c/p\u003e\n \u003cp\u003ePC: 122% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 99 (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: 3.5 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: ND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytosis\u003c/p\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePuerperium;\u003c/p\u003e\n \u003cp\u003ecesarean section\u003c/p\u003e\n \u003cp\u003e(4th day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e275ug/L\u003c/p\u003e\n \u003cp\u003e(0-420)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 73% (N)\u003c/p\u003e\n \u003cp\u003ePC: 129% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 106% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: 8.4 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI: ND\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(8th week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCVT, thrombocytopenia during last pregnancy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e967ug/L\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(0-420)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: 85% (N)\u003c/p\u003e\n \u003cp\u003ePC: 181% (H)\u003c/p\u003e\n \u003cp\u003eATIII: 103% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: 7.9 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePuerperium;\u003c/p\u003e\n \u003cp\u003ecesarean section\u003c/p\u003e\n \u003cp\u003e(11st day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e326\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e5.93\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS: (N)\u003c/p\u003e\n \u003cp\u003ePC: (N)\u003c/p\u003e\n \u003cp\u003eATIII: (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHistory of using ovarian stimulation drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpontaneous incomplete miscarriage (7th day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnemia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003efor \u0026gt;\u0026thinsp;10yrs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e24\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e20.69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePS: 50% (L)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 199% (H)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eATIII: 74% (L)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eAPC-R: 2.5 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSLE (Hematological, kidney, multiple serous fluid accumulation, hypoprotein)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1st trimester\u003c/p\u003e\n \u003cp\u003e(6th week)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1P0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e550\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePS: 45% (L)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 78% (N)\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eATIII: 86% (N)\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eAPC-R: 3(N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eaCL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEssential thrombocythemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ecesarean section;\u003c/p\u003e\n \u003cp\u003ea healthy baby\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003eAbbreviation: PMH, past medical history; L, low; H, high; N, normal; ND, not detected; NA, not available; BMI, body mass index; D-D, D-dimer; aPL, antiphospholipid antibodies; HCY, homocysteine; PC, Protein C; PS, Protein S; ATIII, antithrombin III; APC-R, activated protein C resistance; ANA, anti-nuclear antibody; aCL, anticardiolipin; aB2GPI, anti-\u0026beta;2-glycoprotein I antibodies; LA, lupus anticoagulant; APS, antiphospholipid antibody syndrome; SLE, systemic lupus erythematosus; IDA, iron deficient anemia.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003e\u003csup\u003e*\u003c/sup\u003ePlatelet value was 46\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, platelet surface associated antibody 429 (\u0026lt;\u0026thinsp;128), platelet value returned to normal after induced labor.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eHematology experts suggested follow-up for thrombocytopenia without treatment. Patient refused anticoagulation because of concerns about reduced platelet.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003eRecurrent hand joint pain and morning stiffness during pregnancy. Patient requested transfer and did not complete APS related examinations.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"13\"\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e JAK2 V617F was discovered during follow-up.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 4. Characteristics of patients performed Whole Exome Sequencing\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"95%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e(y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003ePhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003ePregnancy childbirth history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003ePMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003cp\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003eD-D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003eThrombophilia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eaPL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003eHCY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003eWES-\u003c/p\u003e\n \u003cp\u003eLikely pathogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003eWES-\u003c/p\u003e\n \u003cp\u003eUncertain significance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eRisk factors,\u0026nbsp;etiology\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003ePuerperium\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7\u003csup\u003eth\u003c/sup\u003e day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eG1P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e27.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e4.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePS: 28% (L)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 125% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 101% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: \u0026nbsp;2.8 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eACL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e10.8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHeterozygous PROS1\u0026nbsp;\u003c/em\u003e\u003c/strong\u003ec.301C\u0026gt;T (p. Arg101Cys)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003eHeterozygous JAK2 c.2959G\u0026gt;A (p.Glu987Lys)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHereditary\u0026nbsp;PS deficiency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003ePuerperium;\u003c/p\u003e\n \u003cp\u003eSpontaneous labor \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(18\u003csup\u003eth\u003c/sup\u003e day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eG2P2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e22.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.39\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePS: 12% (L)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 75% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 111% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: \u0026nbsp;2.8 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eACL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI (-)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eLA: 1.28(H)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHeterozygous F8\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;c.144-1259C\u0026gt;T\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHeterozygous F8\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ec.6724G\u0026gt;A (p. Val2242Met)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eAPS;\u003c/p\u003e\n \u003cp\u003eHereditary thrombophilia?\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003ePuerperium;\u003c/p\u003e\n \u003cp\u003eSpontaneous labor \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(5\u003csup\u003eth\u003c/sup\u003e day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003ePS: N\u003c/p\u003e\n \u003cp\u003ePC: N\u003c/p\u003e\n \u003cp\u003eATIII: N\u003c/p\u003e\n \u003cp\u003eAPC-R: \u0026nbsp;N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eACL (-)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eaB2GPI \u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e(\u0026plusmn;)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e13.6\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHomozygous MTHFR\u0026nbsp;\u003c/em\u003e\u003c/strong\u003ec.665C\u0026gt;T (p. Ala222Val)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003eHeterozygous MMACHC\u0026nbsp;c.609G\u0026gt;A (p. Trp203*)\u003c/p\u003e\n \u003cp\u003eHeterozygous TMEM199 c.2T\u0026gt;C\u0026nbsp;(p.0?)\u003c/p\u003e\n \u003cp\u003eHeterozygous F13B\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ec.986-15A\u0026gt;G\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eAPS?\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003ePuerperium\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7\u003csup\u003eth\u003c/sup\u003e day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eG1P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e21.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.76\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePS: 62% (L)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003ePC: 98% (N)\u003c/p\u003e\n \u003cp\u003eATIII: 104% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: \u0026nbsp;3.2 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eANA (+)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eACL (+)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eaB2GPI (+)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eLA: 1.32(H)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHomozygous MTHFR\u003c/em\u003e\u003c/strong\u003e c.665C\u0026gt;T (p. Ala222Val)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003eHeterozygous F13A1 c.1081G\u0026gt;A (p.Val361Met)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eAPS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"2.127659574468085%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003csup\u003est\u003c/sup\u003e trimester;\u003c/p\u003e\n \u003cp\u003einduced abortion\u003c/p\u003e\n \u003cp\u003e(11\u003csup\u003eth\u0026nbsp;\u003c/sup\u003eweek)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51063829787234%\" valign=\"top\"\u003e\n \u003cp\u003eG2P1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHealthy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e19.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.319148936170213%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e1.95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.893617021276595%\" valign=\"top\"\u003e\n \u003cp\u003ePS:58% (L)\u0026rarr;78(N)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ePC:39%(L)\u0026rarr;39%(L)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eATIII: 102% (N)\u003c/p\u003e\n \u003cp\u003eAPC-R: \u0026nbsp;2.9 (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.574468085106384%\" valign=\"top\"\u003e\n \u003cp\u003eANA (-)\u003c/p\u003e\n \u003cp\u003eACL (-)\u003c/p\u003e\n \u003cp\u003eaB2GPI\u0026nbsp;(-)\u003c/p\u003e\n \u003cp\u003eLA: N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.25531914893617%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.76595744680851%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eHeterozygous PROC\u003c/em\u003e\u003c/strong\u003e c.1218G\u0026gt;A (p. Met406Ile)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.638297872340425%\" valign=\"top\"\u003e\n \u003cp\u003eHeterozygous F5 c.3331G\u0026gt;A (p.Ala1111Thr)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.382978723404255%\" valign=\"top\"\u003e\n \u003cp\u003eHereditary\u0026nbsp;PC deficiency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviation: PMH, past medical history; L, low; H, high; N, normal; ND, not detected; NA, not available; BMI, body mass index; D-D, D-dimer; aPL, antiphospholipid antibodies; HCY, homocysteine; PC, Protein C; PS, Protein S; ATIII, antithrombin III; APC-R, activated protein C resistance; ANA, anti-nuclear antibody; aCL, anticardiolipin; aB2GPI, anti-\u0026beta;2-glycoprotein I antibodies; LA, lupus anticoagulant.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eCombined pulmonary embolism and inferior vena cava embolism;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003eHigh possibility of APS during follow-up\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCVT is a rare cerebral venous disorder, and pregnant and puerperium women are at increased risk.\u0026nbsp;In the present study, we reported a small retrospective cohort of PCVT, exploring the risk factors and clinical predictors of PCVT and focusing on PCVT patients\u0026rsquo; underlying causes. The characteristics of dehydration, pre-pregnancy anemia, and the presence of anemia, thrombocytopenia and thrombocytosis during pregnancy suggested a greater susceptibility to PCVT. For PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes.\u0026nbsp;Nearly half of 16 patients had no pre-existing medical conditions before pregnancy, and PCVT could be the first manifestation of other diseases. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePregnant and postpartum women are a high-risk group for CVT. Extensive physiological, biochemical, and anatomical changes throughout normal pregnancy and puerperium result in hypercoagulability, hemodynamic alterations, and vascular damage\u003cstrong\u003e\u003cem\u003e(27)\u003c/em\u003e\u003c/strong\u003e. Poor dietary intake, vomiting, excessive sweating, hypovolemia, and anemia could cause hemodynamic changes. Puerperal infections can induce vascular inflammation and systemic vasospasm\u003cstrong\u003e\u003cem\u003e(27, 28)\u003c/em\u003e\u003c/strong\u003e. In our study, most patients developed CVT in the first trimester and postpartum period. The bimodal distribution phenomenon is reasonable\u003cstrong\u003e\u003cem\u003e(29)\u003c/em\u003e\u003c/strong\u003e. Firstly, increased levels of vWF, fibrinogen, and factor VIII may trigger venous thrombosis in particularly susceptible women during early pregnancy. Previous reports suggested that women who have had CVT early on in their pregnancy tend to have another underlying mechanism for their hypercoagulable state such as aPL\u003cstrong\u003e\u003cem\u003e(30)\u003c/em\u003e\u003c/strong\u003e. Secondly, postpartum-related conditions, such as dehydration, and prolonged bed rest might lead to the second peak of PCVT incidence.\u003c/p\u003e\n\u003cp\u003ePrevious studies have reported that anemia was associated with CVT\u003cstrong\u003e\u003cem\u003e(31)\u003c/em\u003e\u003c/strong\u003e. Thrombocytosis, possibly a performance of myeloproliferative neoplasms such as essential thrombocythemia, and thrombocytopenia, possibly a manifestation of APS, were associated with CVT\u003cstrong\u003e\u003cem\u003e(32-34)\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;A cohort covering Pakistan, Turkey, and Mexico showed that anemia and dehydration were the commonest obstetric risk factors identified of PCVT\u003cstrong\u003e\u003cem\u003e(35)\u003c/em\u003e\u003c/strong\u003e. In our study, except for anemia during pregnancy, history of pre-pregnancy anemia was also a significant risk factor for PCVT. However, to best of our knowledge, there was no study on the association of thrombocytosis during pregnancy and PCVT. We first proposed that thrombocytosis and thrombocytopenia during pregnancy were risk factors of PCVT and indicated a predisposition to PCVT. For pregnant and puerperal women without past medical history, anemia, thrombocytosis, and thrombocytopenia might be indicative of a higher risk of PCVT, even the warning of autoimmune diseases, myeloproliferative neoplasms, and other diseases\u003cstrong\u003e\u003cem\u003e(32-34)\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;It was necessary to pay more attention and further search for the causes, such as checking a specific aPL profile.\u003c/p\u003e\n\u003cp\u003eOur study found that autoimmune disease such as APS, hereditary thrombophilia, and hematological disorders were common underlying causes of PCVT, different from the etiologic profiles years ago\u003cstrong\u003e\u003cem\u003e(6, 36)\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;The most common cause in the past was head or neck infections. Economic development, better control of infectious diseases, and a better understanding of the relationship between CVT and autoimmune diseases, hematological disorders and thrombophilia have contributed to this change.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAutoimmune diseases, especially APS, might cause CVT. CVT is a rare complication of APS, with a reported incidence of 0.7%, and on the other hand, APS accounts for a large proportion of about 6-17% of CVT cases\u003cstrong\u003e\u003cem\u003e(34)\u003c/em\u003e\u003c/strong\u003e. Autoimmune diseases were the most common cause, accounting for about 27.8% of CVT cases in women of childbearing age in a previous study at our hospital\u003cstrong\u003e\u003cem\u003e(37)\u003c/em\u003e\u003c/strong\u003e. The neurologic damages caused by APS is related to immune mediated vascular, inflammatory, and direct neuronal effects. Small/microvascular thrombosis and the direct action of aPL, lead to the destruction of the blood-brain barrier, triggering leukocyte adhesion and complement activation, further leading to neurotoxicity of cytokines and antibodies\u003cstrong\u003e\u003cem\u003e(34)\u003c/em\u003e\u003c/strong\u003e. In the present study, about 31% (5/16) of PCVT were diagnosed with APS.\u0026nbsp;Among those five patients, three were completely healthy before pregnancy, and the other two patients had no other symptoms except for spontaneous abortion, suggesting that PCVT could be the first manifestation of APS. The diagnosis of APS is challenging and requires professional immunology experts to combine thrombotic events, adverse pregnancy outcomes, childbirth history, and aPL for a comprehensive evaluation.\u0026nbsp;Besides, there was one patient with SLE who presented with PCVT as the initial manifestation. All patients received immunotherapy to control the primary disease. This highlights the importance of screening for autoimmune diseases in PCVT patients, which was essential for treatment and long-term management.\u003c/p\u003e\n\u003cp\u003eHereditary thrombophilia is an important etiology for CVT, accounting for approximately 34%-41% of cases in cohort studies\u003cstrong\u003e\u003cem\u003e(3)\u003c/em\u003e\u003c/strong\u003e. The most common genetic risk factors for VTE in white individuals, such as FVL, prothrombin G20210A mutation, are rare in Asian populations, while PC, PS, and antithrombin deficiency are important for VTE in Asians\u003cstrong\u003e\u003cem\u003e(38)\u003c/em\u003e\u003c/strong\u003e. PC may inactivate factors Va and VIIIa. Patients with homozygous or compound heterozygous subtypes may present with fulminant purpura in early life, while those with heterozygous subtypes may develop thromboembolism later in life. In our study, we identified one patient with severe PC deficiency, and WES revealed a heterozygous mutation in PROC gene (c.1218G\u0026gt;A, Met406Ile) (Table 4, patient 5). A previous study in Korea\u0026nbsp;reported that Met406Ile was the second most common mutation in VTE patients and was absent in healthy controls\u003cstrong\u003e\u003cem\u003e(39)\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;Met406Ile has also been detected in a Chinese family with VTE\u003cstrong\u003e\u003cem\u003e(40)\u003c/em\u003e\u003c/strong\u003e.\u0026nbsp;The authors used homology modeling to demonstrate that the missense mutation (c.1218C\u0026gt;A, Met406lle) in PROC gene resulted in steric clashes and instability of PC structure, which could impair the normal physiological function of PC and cause hypercoagulability. In addition, 37.5% (6/16) of our patients showed reduced PS activity. Among them, three patients were considered to have gestational PS deficiency. Three patients had severe PS deficiency.\u0026nbsp;One patient had a heterozygous mutation in PROS1 c.301C\u0026gt;T (p. Arg101Cys) (Table 4, patient 1). This mutation has been reported in a case of PS deficiency associated with a partial loss of APC cofactor activity\u003cstrong\u003e\u003cem\u003e(41)\u003c/em\u003e\u003c/strong\u003e. Another patient with low PS activity did not have any PROS1 mutation\u0026nbsp;but had a compound heterozygous mutation in the F8 gene (c.144-1259C\u0026gt;T; c.6724G\u0026gt;A (p. Val2242Met)) (Table 4, patient 2), which might cause\u0026nbsp;X-linked thrombophilia due to factor VIII defect\u003cstrong\u003e\u003cem\u003e(42)\u003c/em\u003e\u003c/strong\u003e. However, we did not perform functional testing to confirm this, which is a limitation and a goal for future research. We speculated that the low PS level may be a consequence of consumption due to the thrombotic process. One patient was suspected to have hereditary PS deficiency but did not undergo WES (Table 3, patient 1). There was no ATIII, FVL, or prothrombin G20210A mutation in our study.\u0026nbsp;These results emphasized the importance of genetic testing for patients with suspected hereditary thrombophilia. In addition, homozygous MTHFR c.665C\u0026gt;T (p. Ala222Val) was considered a risk factor for CVT\u003cstrong\u003e\u003cem\u003e(43)\u003c/em\u003e\u003c/strong\u003e. Hyperhomocysteinemia (HHCY) was reported to be associated with an increased risk of postpartum CVT\u003cstrong\u003e\u003cem\u003e(7)\u003c/em\u003e\u003c/strong\u003e. However, there was no corresponding HHCY in our patients, which may be attributed to regular vitamin supplementation during pregnancy.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHematological disorders are also an important underlying cause of PCVT. JAK2 V617F could cause CVT\u003cstrong\u003e\u003cem\u003e(44)\u003c/em\u003e\u003c/strong\u003e. In our study, we detected this mutation in a patient with essential thrombocythemia during follow-up (Table 1, patient 11), which suggested that genetic testing is necessary for patients with significant thrombocytosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough PCVT is a rare disease, it poses a serious threat to maternal and fetal health. If relevant risk factors could be identified during pregnancy in time, the occurrence of PCVT might be reduced. Hereditary thrombophilia and APS are very important etiologic factors; however, screening for thrombophilia, such as PS and PC activity, and a specific aPL profile was rarely performed during prenatal examinations, which illustrated a lack of understanding of PCVT. For pregnant and puerperium women with dehydration, pre-pregnancy anemia, or combined with anemia, thrombocytopenia, and thrombocytosis, who were more likely to suffer from PCVT, thrombophilia and a specific aPL profile are required, which needs to be further proved in multicenter cohorts.\u003c/p\u003e\n\u003cp\u003eOn the other hand, for confirmed PCVT, it is essential to perform an aggressive etiology screen. Primary disease control is necessary and the optimal duration of anticoagulants depended on the etiology. If CVT was secondary to transient and reversible risk factors, oral anticoagulants could be administered within three months. If the etiology was unknown or associated with a mild hereditary thrombosis, oral anticoagulants should continue for 6- 12 months. For those who suffered from more than two episodes of CVT or had a severe hereditary thrombophilia (e.g.,\u0026nbsp;Prothrombin G20210A homozygous, FVL homozygous, PC, PS, antithrombin deficiency, complex thrombophilia, APS), long-term anticoagulant therapy should be considered\u003cstrong\u003e\u003cem\u003e(26)\u003c/em\u003e\u003c/strong\u003e. For PCVT patients detected no specified etiology, suspected of hereditary thrombophilia, and with significant thrombocytosis or thrombocytopenia, genetic testing may be necessary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has several limitations that should be acknowledged. This is a retrospective study, and information bias and missing data are inevitable. In addition, the small number of patients limited the generalizability of our findings. Due to the limitation of the lack of thrombophilia and aPL data in controls, we failed to build a complete risk model that warrants further investigation in future studies with larger cohorts. Nevertheless, this study still provides valuable data for PCVT, especially in China.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this study emphasizes the necessity of recognizing susceptible pregnant and puerperal women with PCVT and the need for etiological screening.\u0026nbsp;The occur of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. Autoimmune diseases, hereditary thrombophilia, and hematological disorders are common causes for confirmed PCVT patients.\u0026nbsp;It is essential to screen for underlying causes for PCVT, especially hereditary or acquired thrombophilia,\u0026nbsp;which could provide a more comprehensive insight and play a crucial role in long-term management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors state that all methods were carried out in accordance with relevant guidelines and regulations and followed the principles outlined in the Declaration of Helsinki for human. The study was approved by the Ethics Committee of Peking Union Medical College Hospital (JS-2420). Written and informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCapital Medical Development Research funding of China (No. 2020-1-4012).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors would like to thank all the authors of the original articles.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eDepartment of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College \u0026amp; Chinese Academy of Medical Sciences, Beijing, China. \u003csup\u003eb\u003c/sup\u003eDepartment of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College \u0026amp; Chinese Academy of Medical Sciences, Beijing, China \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at\u0026nbsp;Peking Union Medical College Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShaoying Wang: study design, data collection, analysis, and interpretation, drafting of the manuscript; Ming Yao: data collection and interpretation; Nan Hu: contributed to data analysis; Juntao Liu: data collection; Bin Peng: study design, data collection, study supervision and manuscript revision. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict declared.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBousser MG, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol. 2007;6(2):162\u0026ndash;70. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1474-4422(07)70029-7\u003c/span\u003e\u003cspan address=\"10.1016/S1474-4422(07)70029-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eField TS, Hill MD. Cerebral Venous Thrombosis. Stroke. 2019;50(6):1598\u0026ndash;604. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.119.025334\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.119.025334\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555\u0026ndash;65. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrneurol.2017.104\u003c/span\u003e\u003cspan address=\"10.1038/nrneurol.2017.104\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin A, et al. Incidence and Time Trends of Pregnancy-Related Stroke Between 2010 and 2018: The Nationwide CONCEPTION Study. Neurology. 2022;99(15):e1598\u0026ndash;608. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/WNL.0000000000200944\u003c/span\u003e\u003cspan address=\"10.1212/WNL.0000000000200944\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang Z-W, Gao W-L, Feng L-M. Clinical characteristics and prognosis of cerebral venous thrombosis in Chinese women during pregnancy and puerperium. Sci Rep. 2017;7:43866. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/srep43866\u003c/span\u003e\u003cspan address=\"10.1038/srep43866\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLanska DJ, Kryscio RJ. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis. Stroke. 2000;31(6):1274\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNagaraja D, Noone ML, Bharatkumar VP, Christopher R. Homocysteine, folate and vitamin B(12) in puerperal cerebral venous thrombosis. J Neurol Sci. 2008;272(1\u0026ndash;2):43\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jns.2008.03.021\u003c/span\u003e\u003cspan address=\"10.1016/j.jns.2008.03.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDemir CF, et al. Clinical and radiological management and outcome of pregnancies complicated by cerebral venous thrombosis: a review of 19 cases. J Stroke Cerebrovasc Dis. 2013;22(8):1252\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jstrokecerebrovasdis.2012.07.004\u003c/span\u003e\u003cspan address=\"10.1016/j.jstrokecerebrovasdis.2012.07.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChambers DJ, Bhatia K, Columb M. Postpartum cerebral venous sinus thrombosis following obstetric neuraxial blockade: a literature review with analysis of 58 case reports. Int J Obstet Anesth. 2022;49:103218. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ijoa.2021.103218\u003c/span\u003e\u003cspan address=\"10.1016/j.ijoa.2021.103218\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBajko Z, et al. Postpartum Cerebral Venous Thrombosis-A Single-Center Experience. Brain Sci. 2021;11(3). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/brainsci11030327\u003c/span\u003e\u003cspan address=\"10.3390/brainsci11030327\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAaron S, et al. Underlying prothrombotic states in pregnancy associated cerebral venous thrombosis. Neurol India. 2010;58(4):555\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0028-3886.68676\u003c/span\u003e\u003cspan address=\"10.4103/0028-3886.68676\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindagur N, Kruthika-Vinod TP, Christopher R. Thrombophilic gene polymorphisms in puerperal cerebral veno-sinus thrombosis. J Neurol Sci. 2006;249(1):25\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDindagur N, Kruthika-Vinod TP, Christopher R. Factor V gene A4070G mutation and the risk of cerebral veno-sinus thrombosis occurring during puerperium. Thromb Res. 2007;119(4):497\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharpe CJ, Crowther MA, Webert KE, Donnery C. Cerebral venous thrombosis during pregnancy in the setting of type I antithrombin deficiency: case report and literature review. Transfus Med Rev. 2011;25(1):61\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.tmrv.2010.08.007\u003c/span\u003e\u003cspan address=\"10.1016/j.tmrv.2010.08.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUsui M, et al. Cerebral venous sinus thrombosis associated with protein S deficiency during pregnancy: a case report. J Obstet Gynaecol. 2020;40(1):135\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/01443615.2019.1606789\u003c/span\u003e\u003cspan address=\"10.1080/01443615.2019.1606789\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlai S, et al. Maternal cerebral venous thrombosis, uncommon but serious disorder, pathologic predictors and contribution of prothrombotic abnormalities. Blood Coagul Fibrinolysis. 2013;24(3):269\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MBC.0b013e32835bace4\u003c/span\u003e\u003cspan address=\"10.1097/MBC.0b013e32835bace4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDerex L, et al. Postpartum cerebral venous thrombosis, congenital protein C deficiency, and activated protein C resistance due to heterozygous factor V Leiden mutation. J Neurol Neurosurg Psychiatry. 1998;65(5):801\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJianu DC, et al. Diagnosis and Management of Mixed Transcortical Aphasia Due to Multiple Predisposing Factors, including Postpartum and Severe Inherited Thrombophilia, Affecting Multiple Cerebral Venous and Dural Sinus Thrombosis: Case Report and Literature Review. Diagnostics (Basel). 2021;11(8). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/diagnostics11081425\u003c/span\u003e\u003cspan address=\"10.3390/diagnostics11081425\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePleșa FC, et al. Challenges in Cerebral Venous Thrombosis Management-Case Reports and Short Literature Review. Life (Basel). 2023;13(2). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/life13020334\u003c/span\u003e\u003cspan address=\"10.3390/life13020334\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGazioglu S, Dinc G. Cerebral venous sinus thrombosis in pregnancy and puerperium. Acta Neurol Belg. 2021;121(4):967\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s13760-020-01459-3\u003c/span\u003e\u003cspan address=\"10.1007/s13760-020-01459-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAxelerad AD, et al. Case Reports of Pregnancy-Related Cerebral Venous Thrombosis in the Neurology Department of the Emergency Clinical Hospital in Constanta. Life (Basel). 2022;12(1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/life12010090\u003c/span\u003e\u003cspan address=\"10.3390/life12010090\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJeng J-S, Tang S-C, Yip P-K. Incidence and etiologies of stroke during pregnancy and puerperium as evidenced in Taiwanese women. Cerebrovasc Dis. 2004;18(4):290\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang C, et al. Cerebral venous thrombosis as a rare cause of nausea and vomiting in early pregnancy: Case series in a single referral center and literature review. Front Neurol. 2022;13:912419. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2022.912419\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2022.912419\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng S-H, Li J-H, Zuo L-J, Feng L-M. The outcomes of pregnant and postpartum patients with cerebral venous sinus thrombosis after anticoagulant therapy. Med (Baltim). 2021;100(26):e26360. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000026360\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000026360\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao H, Yang B-J, Jin L-P, Jia X-F. Predisposing factors, diagnosis, treatment and prognosis of cerebral venous thrombosis during pregnancy and postpartum: a case-control study. Chin Med J (Engl). 2011;124(24):4198\u0026ndash;204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinese Society of Neurology, Chinese Stroke Society. Chinese guidelines for diagnosis and treatment of cerebral venous thrombosis 2019. Chin J Neurol. 2020;53(09):648\u0026ndash;63. (in Chinese).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTreadwell SD, Thanvi B, Robinson TG. Stroke in pregnancy and the puerperium. Postgrad Med J. 2008;84(991):238\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/pgmj.2007.066167\u003c/span\u003e\u003cspan address=\"10.1136/pgmj.2007.066167\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCamargo EC, Singhal AB. Stroke in Pregnancy: A Multidisciplinary Approach. Obstet Gynecol Clin North Am. 2021;48(1):75\u0026ndash;96. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ogc.2020.11.004\u003c/span\u003e\u003cspan address=\"10.1016/j.ogc.2020.11.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCantu-Brito C, et al. Cerebrovascular complications during pregnancy and postpartum: clinical and prognosis observations in 240 Hispanic women. Eur J Neurol. 2011;18(6):819\u0026ndash;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/j.1468-1331.2010.03259.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1468-1331.2010.03259.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevine SR, et al. Cerebral venous thrombosis with lupus anticoagulants. Report of two cases. Stroke. 1987;18(4):801\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoutinho JM, et al. Association Between Anemia and Cerebral Venous Thrombosis: Case-Control Study. Stroke. 2015;46(10):2735\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/STROKEAHA.115.009843\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.115.009843\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGangat N, et al. Cerebral venous thrombosis and myeloproliferative neoplasms: A three-center study of 74 consecutive cases. Am J Hematol. 2021;96(12):1580\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ajh.26336\u003c/span\u003e\u003cspan address=\"10.1002/ajh.26336\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen W-B, Wang X-L. Cerebral Venous Sinus Thrombosis as the First Manifestation of JAK2V617F-positive Essential Thrombocythemia. Chin Med J (Engl). 2018;131(6):748\u0026ndash;50. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/0366-6999.226903\u003c/span\u003e\u003cspan address=\"10.4103/0366-6999.226903\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeal Rato M, Bandeira M, Rom\u0026atilde;o VC, Aguiar de Sousa D. Neurologic Manifestations of the Antiphospholipid Syndrome - an Update. Curr Neurol Neurosci. 2021;21(8):41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11910-021-01124-z\u003c/span\u003e\u003cspan address=\"10.1007/s11910-021-01124-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan M, et al. Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis. Cerebrovasc Dis. 2023;52(4):393\u0026ndash;400. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000527155\u003c/span\u003e\u003cspan address=\"10.1159/000527155\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQi X, Cui L-Y, Wang J-M. [Changes in clinical characteristics and treatment of cerebral venous and sinus thrombosis: analysis of 35 patients admitted in Peking Union Medical College Hospital]. Zhonghua Yi Xue Za Zhi. 2008;88(23):1624\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Y-T, et al. Clinical Features of CVT in Women and Effect on Subsequent Pregnancy: A Follow-Up Study in a Chinese National Comprehensive Hospital. J Stroke Cerebrovasc Dis. 2020;29(11):105274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jstrokecerebrovasdis.2020.105274\u003c/span\u003e\u003cspan address=\"10.1016/j.jstrokecerebrovasdis.2020.105274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBounameaux H, Rosendaal FR. Venous thromboembolism: why does ethnicity matter? Circulation. 2011;123(20):2189\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCULATIONAHA.111.031690\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.111.031690\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim H-J, et al. Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population. Haematologica. 2014;99(3):561\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3324/haematol.2013.092023\u003c/span\u003e\u003cspan address=\"10.3324/haematol.2013.092023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, et al. [Phenotypic detection and structure analysis of a PC missense mutation (Met406Ile) resulted in venous thromboembolism]. Zhonghua Yi Xue Za Zhi. 2013;93(29):2275\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFranchi F, et al. c.301C\u0026thinsp;\u0026gt;\u0026thinsp;T (p.Arg101Cys): a novel mutation in the thrombin-sensitive region of protein S associated with a dysfunctional protein. Thromb Haemost. 2006;96(3):381\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimioni P, et al. Partial F8 gene duplication (factor VIII Padua) associated with high factor VIII levels and familial thrombophilia. Blood. 2021;137(17):2383\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood.2020008168\u003c/span\u003e\u003cspan address=\"10.1182/blood.2020008168\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalita J, Singh VK, Misra UK. A study of hyperhomocysteinemia in cerebral venous sinus thrombosis. Indian J Med Res. 2020;152(6):584\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4103/ijmr.IJMR_2125_18\u003c/span\u003e\u003cspan address=\"10.4103/ijmr.IJMR_2125_18\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrion D, et al. Janus Kinase-2 V617F Mutation and Antiphospholipid Syndrome in Cerebral Sinus Venous Thrombosis: Natural History and Retrospective Bicenter Analysis. Front Neurol. 2022;13:783795. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fneur.2022.783795\u003c/span\u003e\u003cspan address=\"10.3389/fneur.2022.783795\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Intracranial venous thrombosis, Pregnancy, Risk factor, Thrombophilia, Antiphospholipid syndrome","lastPublishedDoi":"10.21203/rs.3.rs-3852078/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3852078/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo investigate the risk factors and underlying causes of pregnancy-related intracranial venous thrombosis (PCVT).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one were diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G\u0026thinsp;\u0026gt;\u0026thinsp;A (p. Met406Ile), heterozygous PROS1 c.301C\u0026thinsp;\u0026gt;\u0026thinsp;T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C\u0026thinsp;\u0026gt;\u0026thinsp;T; c.6724G\u0026thinsp;\u0026gt;\u0026thinsp;A (p. Val2242Met)) and homozygous MTHFR c.665C\u0026thinsp;\u0026gt;\u0026thinsp;T (p. Ala222Val).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe occur of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.\u003c/p\u003e","manuscriptTitle":"The risk profiles of pregnancy-related intracranial venous thrombosis: a retrospective study in a comprehensive hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 12:10:25","doi":"10.21203/rs.3.rs-3852078/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-17T18:47:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-17T06:19:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-17T06:19:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2024-01-11T02:56:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c0555399-d333-4afd-ba86-2e5b7121d926","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-16T15:30:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 12:10:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3852078","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3852078","identity":"rs-3852078","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}