Severe Cerebral Venous Sinus Thrombosis and Deep Vein Thrombosis Induced by Non-Criteria aPI and aPS/PT Positive Antiphospholipid Antibodies: A Case Report and Mini Review

Severe Cerebral Venous Sinus Thrombosis and Deep Vein Thrombosis Induced by Non-Criteria aPI and aPS/PT Positive Antiphospholipid Antibodies: A Case Report and Mini Review | 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 Case Report Severe Cerebral Venous Sinus Thrombosis and Deep Vein Thrombosis Induced by Non-Criteria aPI and aPS/PT Positive Antiphospholipid Antibodies: A Case Report and Mini Review Ying-Shun He, Feng-Kun Zhang, Xiao-Ling Zhong, Shu-Qin Ma, Qing Zhan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7529173/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Background Antiphospholipid syndrome (APS) is a systemic autoimmune disorder that causes thrombotic events. APS rarely leads to cerebral venous sinus thrombosis (CVST), and it is even more uncommon for non-criteria antiphospholipid antibodies (aPI, aPS/PT-IgM) to contribute to CVST. Case presentation: A 32-year-old male patient was admitted to the hospital with a chief complaint of "headache for five days and limb convulsions for one hour." CT revealed a subarachnoid hemorrhage and a high-density shadow in the right transverse sinus area. CTV and DSA demonstrated a filling defect in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus. Following repeated thrombectomy, venous sinus imaging showed improvement after the removal of a large thrombus. The patient received sequential anticoagulant therapy with low-molecular-weight heparin and warfarin, dehydration therapy with mannitol, nimodipine for cerebral vasospasm prevention, levetiracetam for seizure management, and antibiotics. During treatment, the patient experienced swelling in the left upper limb at the site of an indwelling needle infusion. B-mode ultrasound revealed venous thrombosis in the left axillary and basilic veins. Laboratory tests showed an antinuclear antibody (ANA) titer of 1:100, and positivity for anti-SS-A antibodies. However, a labial gland biopsy revealed only a small number of lymphocytes, ruling out Sjögren’s syndrome. Genetic testing for folate metabolism showed mild abnormalities. The antiphospholipid antibody panel indicated positivity for anti-phosphatidylinositol antibody-IgM (aPI-IgM) and an elevated level of anti-phosphatidylserine/prothrombin complex antibody-IgM (aPS/PT-IgM) at 93.44 ng/mL (normal range: 0–75 ng/mL). Bone marrow cytology was normal. The diagnosis was confirmed as cerebral venous sinus thrombosis due to APS. Four months later, follow-up CTV showed complete resolution of the thrombosis, but the antiphospholipid antibody panel remained positive for aPS/PT-IgM and anti-phosphatidylethanolamine antibody (aPE). Conclusions Non-criteria antiphospholipid antibodies, particularly aPI-IgM and aPS/PT-IgM, can contribute to CVST. Vitamin K antagonists (VKAs) are the preferred anticoagulants, and mechanical thrombectomy should be considered in severe cases. The presence of aPS/PT-IgM may be closely associated with CVST and could serve as a potential molecular marker for APS. Antiphospholipid syndrome Cerebral venous sinus thrombosis aPI-IgM aPS/PT-IgM Intracranial venous sinus thrombectomy Anticoagulation Figures Figure 1 Figure 2 Figure 3 Background Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease primarily affecting young and middle-aged individuals, accounting for 0.5% to 1.0% of all strokes [ 1 ]. CVST most commonly occurs in pregnant women and individuals under 50 years of age with risk factors for hypercoagulability. These factors include oral contraceptive use, genetic disorders, hyperhomocysteinemia, hematologic diseases, autoimmune disorders, various acute and chronic infections, and intracranial or extracranial tumors. However, in some cases, the underlying cause remains unknown [ 2 – 4 ]. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombotic or obstetric complications in individuals with persistently positive antiphospholipid antibodies [ 5 ]. CVST due to APS is uncommon, and cases involving non-criteria antiphospholipid antibodies, such as anti-phosphatidylinositol (aPI) and anti-phosphatidylserine/prothrombin complex (aPS/PT), are even rarer. Here, we report a case of severe CVST and upper extremity deep vein thrombosis in a young man associated with aPI- and aPS/PT-positive atypical APS. Case Presentation A 32-year-old unmarried Chinese male (BMI 27.8) was admitted to the hospital with a five-day history of headache and limb convulsions lasting one hour. An emergency tracheal intubation was performed. His past medical and family history were unremarkable. He did not consume alcohol or use illegal drugs and had no history of neoplasms, trauma, surgery, vaccination, joint pain, or rash prior to disease onset. General and initial neurological examinations were unremarkable. Blood tests at admission revealed an elevated white blood cell (WBC) count of 21.49 × 10 9 /L, D-dimer of 5.67 mg/L, C-reactive protein (CRP) of 21.79 mg/L, and erythrocyte sedimentation rate (ESR) of 28 mm/h. Emergency cerebral computed tomography (CT) showed a subarachnoid hemorrhage and a high-density shadow in the right transverse sinus region (Fig. 1a-b). Enhanced cerebral venous computed tomography (CTV) (Fig. 2a) and digital subtraction angiography (DSA) (Fig. 3a-b) demonstrated filling defects in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus. Cerebral computed tomography angiography (CTA) and DSA did not reveal any intracranial aneurysms. The patient was diagnosed with subarachnoid hemorrhage due to severe CVST with secondary epilepsy. He underwent thrombectomy with suction and vascular stent support more than ten times, leading to the removal of a large volume of thrombi (Fig. 3d). A follow-up DSA confirmed improved cerebral venous sinus imaging (Fig. 3c). Postoperatively, the patient was monitored in the intensive care unit (ICU) and received anticoagulation therapy with low-molecular-weight heparin, mannitol for cerebral edema reduction, nimodipine for cerebral vasospasm prevention, levetiracetam for seizure control, and antibiotics. The patient had no further convulsions, remained conscious and stable, and was subsequently transferred to the neurology department. He was administered sequential anticoagulation therapy with low-molecular-weight heparin and warfarin, along with dehydration therapy using mannitol. His cerebrospinal fluid (CSF) pressure decreased from over 300 mmH 2 O to 270 mmH 2 O, and his headache gradually subsided. During hospitalization, the patient developed swelling in the left upper limb after an injection via an indwelling needle. B-mode ultrasound revealed venous thrombosis in the axillary and basilic veins of the left upper limb. Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (CCP), anti-streptolysin O (ASO), thyroid function tests, and anti-neutrophil cytoplasmic antibodies (cANCA, pANCA) were all within normal ranges. In addition, tumor marker assays—including alpha-fetoprotein (AFP), prostate-specific antigen (PSA), cytokeratin 19 fragment, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9)—showed no abnormalities. Indirect immunofluorescence screening for antinuclear antibodies (ANA) demonstrated a titer of 1:100 with a speckled pattern. Anti-SS-A (SSA) antibodies were positive, but a labial gland biopsy revealed only a small number of lymphocytes, ruling out Sjögren’s syndrome. Blood homocysteine (Hcy) was elevated at 46.11 μmol/L (normal: 0–15), while folic acid (2.3 ng/mL, normal: 3.1–20 ng/mL) and serum vitamin B12 (165 pg/mL, normal: 187–883 pg/mL) were reduced. Genetic testing for folate metabolism showed methylenetetrahydrofolate reductase (MTHFR) mutations CT (C677T, rs1801133) and AC (A1298C, rs1801131), as well as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) mutation AA (A66G, rs1801394), suggesting mild abnormalities in folate metabolism. As a result, folic acid and vitamin supplementation were initiated. Antiphospholipid antibody screening revealed positive anti-phosphatidylinositol antibody-IgM (aPI-IgM, Western blot) and elevated anti-phosphatidylserine/prothrombin complex antibody-IgM (aPS/PT-IgM, 93.44 ng/mL; ELISA, normal: 0–75). However, no abnormalities were detected in anticardiolipin antibody (aCL), anti-β 2 -glycoprotein-1 antibody (aβ 2 GP1), anti-annexin antibodies (aANXA2,5), anti-phosphatidylserine antibody (aPS), anti-prothrombin antibody (aPT), anti-phosphatidylethanolamine antibody (aPE), anti-phosphatidylglycerol antibody (aPG), anti-phosphatidic acid antibody (aPA), anti-protein C antibody, anti-protein S antibody, or β 2 -GP1-Domain1-IgG. White blood cell counts and procalcitonin levels returned to normal. Bone marrow cytology revealed active myeloproliferation, with granulocytes accounting for 48.5%, erythroid precursors for 18%, and a few macrophages displaying pathological changes. Based on these findings, the diagnosis was confirmed as CVST due to non-criteria antiphospholipid syndrome. The patient continued warfarin therapy, maintaining an international normalized ratio (INR) of 2–3, along with antiepileptic treatment (levetiracetam 500 mg twice daily). Given the stable improvement in his condition, hormone and immunosuppressive therapy were not administered. Upon discharge, the patient was asymptomatic, with no headache, limb weakness, or further seizures. Antiepileptic therapy was continued for six months in the absence of recurrent seizures. Follow-up CTV at four months showed complete resolution of thrombosis (Fig. 2B), while antiphospholipid antibody testing remained positive for aPE-IgM (Western blot) and aPS/PT-IgM (79.61 ng/mL, ELISA). Discussion and Conclusion Antiphospholipid antibody (aPL)-mediated thrombosis can occur through multiple mechanisms, including endothelial dysfunction, activation of monocytes, platelets, and neutrophils[6], complement activation, and impaired fibrinolysis [7]. CVST caused by APS is rare, with most reports in the literature being isolated case studies. Severe cerebral sinus thrombosis is even rarer. Alba Jerez-Lienas conducted the largest reported analysis of APS-induced CVST cases, reviewing a total of 27 cases by 2021 [8]. Zhejun Xu retrospectively analyzed 453 APS patients from a single center over an 18-year period (April 2005–August 2023), finding that 8.8% (40/453) of these patients developed CVST. More than 79.5% of the patients exhibited venous sinus thrombosis in multiple sites, with the transverse and sigmoid sinuses being the most commonly affected [9]. The main risk factors for APS-related CVST include oral contraceptive use, intracranial infections, and malignant tumors [9]. Non-criteria antiphospholipid antibodies refer to aPLs beyond lupus anticoagulants (LAs), anticardiolipin antibodies (aCL), and anti-β2-glycoprotein I antibodies (aβ2GP1). These include aPT, aPS, aPI, aPE, aPA, aPG, aPS/PT, aANXA2, aANXA5, among others. Rui Zhu conducted a systematic review of APS cases in PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021, following PRISMA guidelines. This study included 1,853 APS patients (both thrombotic and obstetric) and reported pooled prevalence rates of aPS/PT-IgG, aPS/PT-IgM, and either aPS/PT-IgG or IgM at 50.0%, 45.0%, and 65.0%, respectively. In addition, LA-positive APS patients had an aPS/PT prevalence of 85%, which was comparable to the 84% prevalence observed in triple aPL-positive patients [10]. Siting Li found that 23 out of 24 APS patients who tested negative for standard serological markers were positive for at least one non-criteria aPL [11]. aPI-IgG and aPG-IgG have been linked to stroke in affected patients [12], but aPI-induced intracranial venous thrombosis has not been previously reported. aPS/PT-IgM has been associated with heart valve damage [13] and cutaneous vasculitis [14], and its thrombosis risk increases when LAs are present [15]. Positive aPS/PT is strongly correlated with thrombosis [10]. Savino Sciascia systematically reviewed Medline reports published between 1988 and 2013, examining aPT and aPS/PT as risk factors for thrombosis. The findings indicated that antibodies against prothrombin (both aPT and aPS/PT) increase the risk of thrombosis, with aPS/PT being a particularly strong predictor of embolization in both arterial and venous systems [16]. Furthermore, aPS/PT-IgG is associated with deep vein thrombosis (DVT) [11]. The simultaneous presence of APS-related non-criteria antiphospholipid antibodies (aPI, aPS/PT-IgM) leading to CVST is exceedingly rare. CVST presents in various forms with diverse clinical manifestations. Headache is the most common symptom, occurring in approximately 90% of patients, while about 40% experience partial or generalized epileptic seizures [17]. In this study, the patient initially presented with headache and generalized seizures. CT imaging revealed subarachnoid hemorrhage, likely due to a significant increase in intracranial pressure caused by CVST. High-density cerebral venous sinus imaging was confirmed by CTV and DSA, establishing the diagnosis of cerebral venous sinus thrombosis [18]. Other potential causes, including tumors, infections, and autoimmune diseases, were ruled out. In addition to cerebral venous sinus thrombosis, secondary venous thrombosis was observed in the axillary and basilic veins of the left upper limb, consistent with previous reports [11,18]. According to the 2023 classification criteria for antiphospholipid syndrome established by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), the patient met the criteria for APS, presenting with CVST and upper limb deep vein thrombosis without significant major or secondary risk factors (score: 3 points) [19]. Notably, cerebral venous sinus thrombosis resolved completely following anticoagulant therapy. Despite negative results for LA, aCL, and aβ2GP1, non-criteria antiphospholipid antibodies, specifically aPS/PT-IgM, remained persistently positive, with aPI and aPE subsequently testing positive as well. We conclude that the patient’s CVST and upper extremity DVT were associated with non-criteria APS antibodies, particularly aPS/PT. Patients with aPS/PT positivity exhibit a higher prevalence of APS associated with other autoimmune diseases compared to primary APS, highlighting the link between aPS/PT and autoimmune conditions. This raises concerns regarding the specificity of aPS/PT in diagnosing APS and the potential for overdiagnosis if aPS/PT is included as a first-line diagnostic marker. In second-line testing, aPS/PT may help confirm APS diagnosis in high-risk patients [20]. Furthermore, in certain situations where LA testing is unreliable or inconclusive, aPS/PT can serve as a valuable diagnostic tool [21]. Future research is expected to further validate aPS/PT as a standard laboratory marker for APS. aPS/PT-IgG and anti-β2 glycoprotein I domain 1 (aβ2GPI-D1) IgG appear to be the most significant risk factors for thrombotic events and pregnancy-related complications [21]. Additionally, aPS/PT is a key component of the Global Antiphospholipid Syndrome Score (GAPSS), which helps assess a patient’s risk of thrombosis. Non-criteria obstetric antiphospholipid syndrome (NCOAPS) includes aPS/PT, glycoprotein, and aβ2GPI-D1 antibodies [22]. In this case, the patient remained positive for aPS/PT for four months, further supporting the relevance of these antibodies in APS diagnosis. Future studies will likely reinforce the role of aPS/PT as a standard laboratory marker for APS. Adequate and continuous anticoagulation is crucial for venous sinus recanalization and for reducing the risk of thrombosis recurrence [9]. For APS-induced CVST, vitamin K antagonists (VKAs) with a target INR of 2.0–3.0 are preferred over direct oral anticoagulants (DOACs), as the latter may carry a higher risk of recurrent thromboembolic events [23,24]. In severe cases, where venous thrombosis causes a mass effect or intracranial hypertension due to hemorrhage, conventional medical management may be insufficient, necessitating mechanical thrombectomy or intracranial venous stent placement [25,26]. Imaging findings in this case indicated severe cerebral venous sinus thrombosis, which could not be effectively resolved with anticoagulation alone [27–32]. Consequently, the patient underwent endovascular thrombectomy, resulting in the removal of a substantial thrombus burden and the restoration of cerebral blood flow. Anticoagulation therapy was initiated postoperatively, and follow-up imaging confirmed complete resolution, with full recanalization of the cerebral venous sinuses. In cases of catastrophic antiphospholipid syndrome (CAPS), immunosuppressants or corticosteroids may be required [33]. This case highlights the role of non-criteria APS antibodies in severe CVST. In clinical practice, APS should be considered when evaluating the etiology of CVST, particularly in the presence of non-criteria antibodies. Accurate diagnosis and appropriate treatment are essential. For severe APS-related CVST, thrombectomy may be a viable treatment option, followed by long-term anticoagulation to prevent recurrence. Declarations Ethics approval and consent to participate This case report was approved by the Ethics Committee for clinical medical research of Zhejiang University Sir Run Run Shaw Alar Hospital. Consent for publication The written informed consent has been obtained from the patient for publication of this case report and any accompanying images. Availability of data and materials Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Competing interests The authors declare that they have no competing interests. Funding Project Supported by Science and Technology Plan Project of the First Division（Grant No: 2024YL01）. Authors’ contributions YSH,FKZ,XLZ,SQM,QZ evaluated and managed the patient.YSH,WMW wrote the manuscript and prepared the figures. ZXZ revised the manuscript for important intellectual content and finalized the manuscript. All authors read and approved the final manuscript. Acknowledgements n/a References Gayathri K, Ramalingam PK, Santhakumar R, Manjunath BV, Karuppuswamy N, Vetriveran B, Selvamani S, Vishnuram P, Natarajan K. Cerebral sinus venous thrombosis as a rare complication of primary varicella zoster virus infection. J Assoc Physicians India, 2016, 64:74⁃76. Field TS, Hill MD. Cerebral venous thrombosis: we should ask the right questions to get better answers[J]. Stroke, 2019, 50(6): 1598-1604. DOI: 10.1161/STROKEAHA.119.025334. Ropper AH, Klein JP. Cerebral Venous Thrombosis[J]. N Engl J Med, 2021, 385(1): 59-64. DOI: 10.1056/NEJMra2106545. Saposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a state ment for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2011, 42(4): 1158-1192. DOI: 10.1161/STR.0b013e31820a8364 Sammaritano LR. Antiphospholipid syndrome[J]. Best Pract Res Clin Rheumatol, 2020, 34(1): 101463. DOI: 10.1016/j.berh. 2019.101463. Garcia D, Erkan D.Diagnosis and management of the antiphospholipid syndrome[J]. N Engl J Med,2018,378(21):2010-2021. Chaturvedi S，Braunstein EM，Yuan X，et al． Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS ［J］． Blood，2020，135( 4) : 239-251. Alba Jerez-Lienas , Alexis Mathian , Jenifer Aboab，et al．Cerebral Vein Thrombosis in the Antiphospholipid Syndrome: Analysis of a Series of 27 Patients and Review of the Literature, Brain Sci. 2021 Dec 13;11(12):1641. doi: 10.3390/brainsci11121641. Zhejun Xu , Can Huang , Hui Jiang ，et al．Clinical characteristics and outcomes of cerebral venous sinus thrombosis in patients with antiphospholipid syndrome.Clin Rheumatol，2024 Dec;43(12):3747-3757. doi: 10.1007/s10067-024-07205-x. Epub 2024 Oct 31. Rui Zhu , Chun-Yan Cheng , Yan Yang,et,al.Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis. Thromb Res. 2022 Jun:214:106-114. doi: 10.1016/j.thromres.2022.04.021.Epub 2022 May 2. Siting Li , Yina Bai , Jingjing Meng ,et,al.Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients. Front Immunol. 2023 Apr 12:14:1107510. doi: 10.3389/fimmu.2023.1107510. eCollection 2023. Siting Li , Jiulang Zhao , Yina Bai ,et,al.Profile and clinical relevance of non-criteria antiphospholipid antibodies in patients diagnosed with or highly suspected of APS. Rheumatology (Oxford). 2024 Mar 1;63(3):891-900. doi: 10.1093/rheumatology/kead303. Tamihiro Kawakami , Ayaka Kikuchi , Chie Miyabe , et,al.Relationship between lysosomal-associated membrane protein-2 and anti-phosphatidylserine/prothrombin complex antibody in the pathogenesis of cutaneous vasculitis. Clin Exp Rheumatol. 2020 Mar-Apr;38 Suppl 124(2):161-165. Epub 2020 Jan 27. Yuncong Zhang , Yang Su , Han Guo , et, al.Anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) increase the risk for thrombosis based on lupus anticoagulant positivity. Clin Biochem. 2023 Feb:112:17-23. doi: 10.1016/j.clinbiochem.2022.12.007. Epub 2022 Dec 16. Poon CS, Chang JK, Swarnkar A, Johnson MH, Wasenko J. Radiologic diagnosis of cerebral venous thrombosis: pictorial review. AJR Am J Roentgenol, 2007, 189(6 Suppl):64⁃75. Savino Sciascia, Giovanni Sanna, Veronica Murru,et,al.Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost. 2014 Feb;111(2):354-64. doi: 10.1160/TH13-06-0509.Epub 2013 Oct 31. Janjua N. Cerebral angiography and venography for evaluation of cerebral venous thrombosis. J Pak Med Assoc, 2006, 56:527⁃ 530. Shingo Sakamoto , Koichi Akutsu, Kayoko Kawase,et,al.Simultaneous presentations of deep vein thrombosis and cerebral sinus thrombosis in a case of primary antiphospholipid syndrome, Angiology. 2008;59(6):765-8. doi: 10.1177/0003319707309310.Epub 2008 Apr 2. Deepa J. Arachchillage1, Sean Platton, Kieron Hickey, et, at. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2024;205:855–880. DOI: 10.1111/bjh.19635. Katrien M. J. Devreese,Maria Laura Bertolaccini,D. Ware Branch, et, al. An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. J Thromb Haemost. 2025;23:731–744. Tingting Liu , Jieyu Gu , Liyan Wan , et,al."Non-criteria" antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res Ther. 2020 Feb 21;22(1):33. doi: 10.1186/s13075-020-2131-4. Rui Gao , Lang Qin，Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues[Article in Chinese] . Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 May 20;55(3):513-520.doi: 10.12182/20240560104. Woller SC, Stevens SM, Kaplan D, et al. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphos pholipid syndrome: a randomized trial[J]. Blood Adv, 2022, 6(6): 1661-1670. DOI: 10.1182/bloodadvances.2021005808. Tektonidou MG, Andreoli L, Limper M, et al. EULAR recom mendations for the management of antiphospholipid syn drome in adults[J]. Ann Rheum Dis, 2019, 78(10): 1296-1304. DOI: 10.1136/annrheumdis-2019-215213. Cao XY, Li BM, Li S, Wang J, Ma YD, Liu XF, Liang YP, Ge AL, Zhang AL. Angiography and clinical analysis of intracranial venous sinus in jugular foramen. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2013, 13:222⁃225. Dashti SR, Hu YC, Yao T, Fiorella D, Mitha AP, Albuquerque FC, McDougall CG. Mechanical thrombectomy as first ⁃ line treatment for venous sinus thrombosis: technical considerations and preliminary results using the AngioJet device. J Neurointerv Surg, 2013, 5:49⁃53. De Bruijn SF, Stam J. Randomized, placebo controlled trial of anticoagulant treatment with low molecular weight heparin for cerebral sinus thrombosis. Stroke, 1999, 30:484⁃488. Stam J. Sinus thrombosis should be treated with anticoagulation. Arch Neurol, 2008, 6:984⁃985. Coutinho J, de Bruijn SF, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev, 2011, 10(8):CD002005. Mehraein S, Schmidtke K, Villringer A, Valdueza JM, Masuhr F. Heparin treatment in cerebral sinus and venous thrombosis: patients at risk of fatal outcome. Cerebrovasc Dis, 2003, 15:17⁃ 21. Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2011, 42:1158⁃1192. Einhäupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, Masuhr F; European Federation of Neurological Societies. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol, 2010, 17: 1229⁃1235. Atalay Doğru , Yunus Ugan , Mehmet Şahin,et,al. Catastrophic antiphospholipid syndrome treated with rituximab: A case report. Eur J Rheumatol. 2017 Jun;4(2):145-147. doi: 10.5152/eurjrheum.2017.160073. Epub 2017 Jun 1. Additional Declarations No competing interests reported. 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1","display":"","copyAsset":false,"role":"figure","size":168937,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHead CT scans.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) High-density imaging of the right transverse sinus (red arrows).\u003c/p\u003e\n\u003cp\u003e(B) Subarachnoid hemorrhage (red arrows).\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7529173/v1/b24db4ebc4d0c98f17791a7f.jpeg"},{"id":95806924,"identity":"ffcf773b-cef8-47f9-99d9-4991981c0d81","added_by":"auto","created_at":"2025-11-13 08:48:00","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":62976,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCerebral venous CT venography (CTV).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A)Preoperative scan showing a filling defect in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus (yellow arrows).\u003c/p\u003e\n\u003cp\u003e(B) Follow-up scan four months after surgery showing complete recovery of the cerebral venous sinus.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7529173/v1/f4fbaf2a9ef8c08926d40156.jpeg"},{"id":95806612,"identity":"ec4c9984-770d-4445-8956-3d92e83bf4da","added_by":"auto","created_at":"2025-11-13 08:47:43","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":161847,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDigital subtraction angiography (DSA).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A)Preoperative imaging showing a filling defect in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus (red arrows).\u003c/p\u003e\n\u003cp\u003e(B) Normalleft venous sinus (yellow arrows).\u003c/p\u003e\n\u003cp\u003e(C)Postoperative imaging demonstrating significant improvement in right venous sinus perfusion (red arrows).\u003c/p\u003e\n\u003cp\u003e(D) Thrombus partially removed during surgery.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7529173/v1/41100fd60809f1947f9d62b2.jpeg"},{"id":95819856,"identity":"7649a142-733e-48c9-a509-ae5ec3e5a38f","added_by":"auto","created_at":"2025-11-13 10:43:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":813901,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7529173/v1/bc60ad9f-67e6-4252-b1dc-f1c29ba064ed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Severe Cerebral Venous Sinus Thrombosis and Deep Vein Thrombosis Induced by Non-Criteria aPI and aPS/PT Positive Antiphospholipid Antibodies: A Case Report and Mini Review","fulltext":[{"header":"Background","content":"\u003cp\u003eCerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disease primarily affecting young and middle-aged individuals, accounting for 0.5% to 1.0% of all strokes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCVST most commonly occurs in pregnant women and individuals under 50 years of age with risk factors for hypercoagulability. These factors include oral contraceptive use, genetic disorders, hyperhomocysteinemia, hematologic diseases, autoimmune disorders, various acute and chronic infections, and intracranial or extracranial tumors. However, in some cases, the underlying cause remains unknown [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAntiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombotic or obstetric complications in individuals with persistently positive antiphospholipid antibodies [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. CVST due to APS is uncommon, and cases involving non-criteria antiphospholipid antibodies, such as anti-phosphatidylinositol (aPI) and anti-phosphatidylserine/prothrombin complex (aPS/PT), are even rarer. Here, we report a case of severe CVST and upper extremity deep vein thrombosis in a young man associated with aPI- and aPS/PT-positive atypical APS.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 32-year-old unmarried Chinese male (BMI 27.8) was admitted to the hospital with a five-day history of headache and limb convulsions lasting one hour. An emergency tracheal intubation was performed. His past medical and family history were unremarkable. He did not consume alcohol or use illegal drugs and had no history of neoplasms, trauma, surgery, vaccination, joint pain, or rash prior to disease onset.\u003c/p\u003e\n\u003cp\u003eGeneral and initial neurological examinations were unremarkable. Blood tests at admission revealed an elevated white blood cell (WBC) count of 21.49 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L, D-dimer of 5.67 mg/L, C-reactive protein (CRP) of 21.79 mg/L, and erythrocyte sedimentation rate (ESR) of 28 mm/h. Emergency cerebral computed tomography (CT) showed a subarachnoid hemorrhage and a high-density shadow in the right transverse sinus region (Fig. 1a-b). Enhanced cerebral venous computed tomography (CTV) (Fig. 2a) and digital subtraction angiography (DSA) (Fig. 3a-b) demonstrated filling defects in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus. Cerebral computed tomography angiography (CTA) and DSA did not reveal any intracranial aneurysms.\u003c/p\u003e\n\u003cp\u003eThe patient was diagnosed with subarachnoid hemorrhage due to severe CVST with secondary epilepsy. He underwent thrombectomy with suction and vascular stent support more than ten times, leading to the removal of a large volume of thrombi (Fig. 3d). A follow-up DSA confirmed improved cerebral venous sinus imaging (Fig. 3c).\u003c/p\u003e\n\u003cp\u003ePostoperatively, the patient was monitored in the intensive care unit (ICU) and received anticoagulation therapy with low-molecular-weight heparin, mannitol for cerebral edema reduction, nimodipine for cerebral vasospasm prevention, levetiracetam for seizure control, and antibiotics.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient had no further convulsions, remained conscious and stable, and was subsequently transferred to the neurology department. He was administered sequential anticoagulation therapy with low-molecular-weight heparin and warfarin, along with dehydration therapy using mannitol. His cerebrospinal fluid (CSF) pressure decreased from over 300 mmH\u003csub\u003e2\u003c/sub\u003eO to 270 mmH\u003csub\u003e2\u003c/sub\u003eO, and his headache gradually subsided. During hospitalization, the patient developed swelling in the left upper limb after an injection via an indwelling needle. B-mode ultrasound revealed venous thrombosis in the axillary and basilic veins of the left upper limb. Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (CCP), anti-streptolysin O (ASO), thyroid function tests, and anti-neutrophil cytoplasmic antibodies (cANCA, pANCA) were all within normal ranges. In addition, tumor marker assays\u0026mdash;including alpha-fetoprotein (AFP), prostate-specific antigen (PSA), cytokeratin 19 fragment, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9)\u0026mdash;showed no abnormalities.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIndirect immunofluorescence screening for antinuclear antibodies (ANA) demonstrated a titer of 1:100 with a speckled pattern. Anti-SS-A (SSA) antibodies were positive, but a labial gland biopsy revealed only a small number of lymphocytes, ruling out Sj\u0026ouml;gren\u0026rsquo;s syndrome. Blood homocysteine (Hcy) was elevated at 46.11 \u0026mu;mol/L (normal: 0\u0026ndash;15), while folic acid (2.3 ng/mL, normal: 3.1\u0026ndash;20 ng/mL) and serum vitamin B12 (165 pg/mL, normal: 187\u0026ndash;883 pg/mL) were reduced. Genetic testing for folate metabolism showed methylenetetrahydrofolate reductase (MTHFR) mutations CT (C677T, rs1801133) and AC (A1298C, rs1801131), as well as 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) mutation AA (A66G, rs1801394), suggesting mild abnormalities in folate metabolism. As a result, folic acid and vitamin supplementation were initiated. Antiphospholipid antibody screening revealed positive anti-phosphatidylinositol antibody-IgM (aPI-IgM, Western blot) and elevated anti-phosphatidylserine/prothrombin complex antibody-IgM (aPS/PT-IgM, 93.44 ng/mL; ELISA, normal: 0\u0026ndash;75). However, no abnormalities were detected in anticardiolipin antibody (aCL), anti-\u0026beta;\u003csub\u003e2\u003c/sub\u003e-glycoprotein-1 antibody (a\u0026beta;\u003csub\u003e2\u003c/sub\u003eGP1), anti-annexin antibodies (aANXA2,5), anti-phosphatidylserine antibody (aPS), anti-prothrombin antibody (aPT), anti-phosphatidylethanolamine antibody (aPE), anti-phosphatidylglycerol antibody (aPG), anti-phosphatidic acid antibody (aPA), anti-protein C antibody, anti-protein S antibody, or \u0026beta;\u003csub\u003e2\u003c/sub\u003e-GP1-Domain1-IgG. White blood cell counts and procalcitonin levels returned to normal. Bone marrow cytology revealed active myeloproliferation, with granulocytes accounting for 48.5%, erythroid precursors for 18%, and a few macrophages displaying pathological changes. Based on these findings, the diagnosis was confirmed as CVST due to non-criteria antiphospholipid syndrome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patient continued warfarin therapy, maintaining an international normalized ratio (INR) of 2\u0026ndash;3, along with antiepileptic treatment (levetiracetam 500 mg twice daily). Given the stable improvement in his condition, hormone and immunosuppressive therapy were not administered. Upon discharge, the patient was asymptomatic, with no headache, limb weakness, or further seizures. Antiepileptic therapy was continued for six months in the absence of recurrent seizures. Follow-up CTV at four months showed complete resolution of thrombosis (Fig. 2B), while antiphospholipid antibody testing remained positive for aPE-IgM (Western blot) and aPS/PT-IgM (79.61 ng/mL, ELISA).\u003c/p\u003e"},{"header":"Discussion and Conclusion","content":"\u003cp\u003eAntiphospholipid antibody (aPL)-mediated thrombosis can occur through multiple mechanisms, including endothelial dysfunction, activation of monocytes, platelets, and neutrophils[6], complement activation, and impaired fibrinolysis [7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCVST caused by APS is rare, with most reports in the literature being isolated case studies. Severe cerebral sinus thrombosis is even rarer. Alba Jerez-Lienas conducted the largest reported analysis of APS-induced CVST cases, reviewing a total of 27 cases by 2021 [8]. Zhejun Xu retrospectively analyzed 453 APS patients from a single center over an 18-year period (April 2005\u0026ndash;August 2023),\u0026nbsp;finding that\u0026nbsp;8.8% (40/453)\u0026nbsp;of these\u0026nbsp;patients developed CVST. More than 79.5% of the patients\u0026nbsp;exhibited\u0026nbsp;venous sinus thrombosis in\u0026nbsp;multiple\u0026nbsp;sites,\u0026nbsp;with\u0026nbsp;the transverse and sigmoid\u0026nbsp;sinuses being the most commonly affected [9]. The main risk factors for APS-related CVST include oral contraceptive use, intracranial infections,\u0026nbsp;and malignant tumors [9].\u003c/p\u003e\n\u003cp\u003eNon-criteria antiphospholipid antibodies refer to aPLs beyond lupus anticoagulants (LAs), anticardiolipin antibodies (aCL), and anti-\u0026beta;2-glycoprotein I antibodies (a\u0026beta;2GP1). These include aPT, aPS, aPI, aPE, aPA, aPG, aPS/PT, aANXA2, aANXA5, among others. Rui Zhu conducted a systematic review of APS cases in PubMed, Web of Science, and the Cochrane Library from January 1990 to September 2021, following PRISMA guidelines. This study included 1,853 APS patients (both thrombotic and obstetric) and reported pooled prevalence rates of aPS/PT-IgG, aPS/PT-IgM, and either aPS/PT-IgG or IgM at 50.0%, 45.0%, and 65.0%, respectively. In addition, LA-positive APS patients had an aPS/PT prevalence of 85%, which was comparable to the 84% prevalence observed in triple aPL-positive patients [10]. Siting Li found that 23 out of 24 APS patients who tested negative for standard serological markers were positive for at least one non-criteria aPL [11].\u003c/p\u003e\n\u003cp\u003eaPI-IgG and aPG-IgG have been linked to stroke in affected patients [12], but aPI-induced intracranial venous thrombosis has not been previously reported. aPS/PT-IgM has been associated with heart valve damage [13] and cutaneous vasculitis [14], and its thrombosis risk increases when LAs are present [15]. Positive aPS/PT is strongly correlated with thrombosis [10]. Savino Sciascia systematically reviewed Medline reports published between 1988 and 2013, examining aPT and aPS/PT as risk factors for thrombosis. The findings indicated that antibodies against prothrombin (both aPT and aPS/PT) increase the risk of thrombosis, with aPS/PT being a particularly strong predictor of embolization in both arterial and venous systems [16]. Furthermore, aPS/PT-IgG is associated with deep vein thrombosis (DVT) [11].\u003c/p\u003e\n\u003cp\u003eThe simultaneous presence of APS-related non-criteria antiphospholipid antibodies (aPI, aPS/PT-IgM) leading to CVST is exceedingly rare. CVST presents in various forms with diverse clinical manifestations. Headache is the most common symptom, occurring in approximately 90% of patients, while about 40% experience partial or generalized epileptic seizures [17]. In this study, the patient initially presented with headache and generalized seizures. CT imaging revealed subarachnoid hemorrhage, likely due to a significant increase in intracranial pressure caused by CVST. High-density cerebral venous sinus imaging was confirmed by CTV and DSA, establishing the diagnosis of cerebral venous sinus thrombosis [18]. Other potential causes, including tumors, infections, and autoimmune diseases, were ruled out. In addition to cerebral venous sinus thrombosis, secondary venous thrombosis was observed in the axillary and basilic veins of the left upper limb, consistent with previous reports [11,18].\u003c/p\u003e\n\u003cp\u003eAccording to the 2023 classification criteria for antiphospholipid syndrome established by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), the patient met the criteria for APS, presenting with CVST and upper limb deep vein thrombosis without significant major or secondary risk factors (score: 3 points) [19]. Notably, cerebral venous sinus thrombosis resolved completely following anticoagulant therapy. Despite negative results for LA, aCL, and a\u0026beta;2GP1, non-criteria antiphospholipid antibodies, specifically aPS/PT-IgM, remained persistently positive, with aPI and aPE subsequently testing positive as well. We conclude that the patient\u0026rsquo;s CVST and upper extremity DVT were associated with non-criteria APS antibodies, particularly aPS/PT.\u003c/p\u003e\n\u003cp\u003ePatients with aPS/PT positivity exhibit a higher prevalence of APS associated with other autoimmune diseases compared to primary APS, highlighting the link between aPS/PT and autoimmune conditions. This raises concerns regarding the specificity of aPS/PT in diagnosing APS and the potential for overdiagnosis if aPS/PT is included as a first-line diagnostic marker. In second-line testing, aPS/PT may help confirm APS diagnosis in high-risk patients [20]. Furthermore, in certain situations where LA testing is unreliable or inconclusive, aPS/PT can serve as a valuable diagnostic tool [21]. Future research is expected to further validate aPS/PT as a standard laboratory marker for APS.\u003c/p\u003e\n\u003cp\u003eaPS/PT-IgG and anti-\u0026beta;2 glycoprotein I domain 1 (a\u0026beta;2GPI-D1) IgG appear to be the most significant risk factors for thrombotic events and pregnancy-related complications [21]. Additionally, aPS/PT is a key component of the Global Antiphospholipid Syndrome Score (GAPSS), which helps assess a patient\u0026rsquo;s risk of thrombosis. Non-criteria obstetric antiphospholipid syndrome (NCOAPS) includes aPS/PT, glycoprotein, and a\u0026beta;2GPI-D1 antibodies [22]. In this case, the patient remained positive for aPS/PT for four months, further supporting the relevance of these antibodies in APS diagnosis. Future studies will likely reinforce the role of aPS/PT as a standard laboratory marker for APS.\u003c/p\u003e\n\u003cp\u003eAdequate and continuous anticoagulation is crucial for venous sinus recanalization and for reducing the risk of thrombosis recurrence [9]. For APS-induced CVST, vitamin K antagonists (VKAs) with a target INR of 2.0\u0026ndash;3.0 are preferred over direct oral anticoagulants (DOACs), as the latter may carry a higher risk of recurrent thromboembolic events [23,24]. In severe cases, where venous thrombosis causes a mass effect or intracranial hypertension due to hemorrhage, conventional medical management may be insufficient, necessitating mechanical thrombectomy or intracranial venous stent placement [25,26].\u003c/p\u003e\n\u003cp\u003eImaging findings in this case indicated severe cerebral venous sinus thrombosis, which could not be effectively resolved with anticoagulation alone [27\u0026ndash;32]. Consequently, the patient underwent endovascular thrombectomy, resulting in the removal of a substantial thrombus burden and the restoration of cerebral blood flow. Anticoagulation therapy was initiated postoperatively, and follow-up imaging confirmed complete resolution, with full recanalization of the cerebral venous sinuses. In cases of catastrophic antiphospholipid syndrome (CAPS), immunosuppressants or corticosteroids may be required [33].\u003c/p\u003e\n\u003cp\u003eThis case highlights the role of non-criteria APS antibodies in severe CVST. In clinical practice, APS should be considered when evaluating the etiology of CVST, particularly in the presence of non-criteria antibodies. Accurate diagnosis and appropriate treatment are essential. For severe APS-related CVST, thrombectomy may be a viable treatment option, followed by long-term anticoagulation to prevent recurrence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis case report was approved by the Ethics Committee for clinical medical research of Zhejiang University Sir Run Run Shaw Alar Hospital.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eThe written informed consent has been obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProject Supported by Science and Technology Plan Project of the First Division（Grant No: 2024YL01）.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo;\u0026nbsp;contributions\u003c/p\u003e\n\u003cp\u003eYSH,FKZ,XLZ,SQM,QZ evaluated and managed the patient.YSH,WMW wrote the manuscript and prepared the figures. ZXZ revised the manuscript for important intellectual content and finalized the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003en/a\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGayathri K, Ramalingam PK, Santhakumar R, Manjunath BV, Karuppuswamy N, Vetriveran B, Selvamani S, Vishnuram P, Natarajan K. Cerebral sinus venous thrombosis as a rare complication of primary varicella zoster virus infection. J Assoc Physicians India, 2016, 64:74⁃76.\u003c/li\u003e\n\u003cli\u003eField TS, Hill MD. Cerebral venous thrombosis: we should ask the right questions to get better answers[J]. Stroke, 2019, 50(6): 1598-1604. DOI: 10.1161/STROKEAHA.119.025334. \u003c/li\u003e\n\u003cli\u003eRopper AH, Klein JP. Cerebral Venous Thrombosis[J]. N Engl J Med, 2021, 385(1): 59-64. DOI: 10.1056/NEJMra2106545.\u003c/li\u003e\n\u003cli\u003eSaposnik G, Barinagarrementeria F, Brown RD Jr, et al. Diagnosis and management of cerebral venous thrombosis: a state ment for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2011, 42(4): 1158-1192. DOI: 10.1161/STR.0b013e31820a8364\u003c/li\u003e\n\u003cli\u003eSammaritano LR. Antiphospholipid syndrome[J]. Best Pract Res Clin Rheumatol, 2020, 34(1): 101463. DOI: 10.1016/j.berh. 2019.101463.\u003c/li\u003e\n\u003cli\u003eGarcia D, Erkan D.Diagnosis and management of the antiphospholipid syndrome[J]. N Engl J Med,2018,378(21):2010-2021.\u003c/li\u003e\n\u003cli\u003eChaturvedi S，Braunstein EM，Yuan X，et al． Complement activity and complement regulatory gene mutations are associated with thrombosis in APS and CAPS ［J］． Blood，2020，135( 4) : 239-251.\u003c/li\u003e\n\u003cli\u003eAlba Jerez-Lienas , Alexis Mathian , Jenifer Aboab，et al．Cerebral Vein Thrombosis in the Antiphospholipid Syndrome: Analysis of a Series of 27 Patients and Review of the Literature, Brain Sci. 2021 Dec 13;11(12):1641. doi: 10.3390/brainsci11121641.\u003c/li\u003e\n\u003cli\u003eZhejun Xu , Can Huang , Hui Jiang ，et al．Clinical characteristics and outcomes of cerebral venous sinus thrombosis in patients with antiphospholipid syndrome.Clin Rheumatol，2024 Dec;43(12):3747-3757. doi: 10.1007/s10067-024-07205-x. Epub 2024 Oct 31.\u003c/li\u003e\n\u003cli\u003eRui Zhu , Chun-Yan Cheng , Yan Yang,et,al.Prevalence of aPhosphatidylserine/prothrombin antibodies and association with antiphospholipid antibody profiles in patients with antiphospholipid syndrome: A systematic review and meta-analysis. Thromb Res. 2022 Jun:214:106-114. doi: 10.1016/j.thromres.2022.04.021.Epub 2022 May 2.\u003c/li\u003e\n\u003cli\u003eSiting Li , Yina Bai , Jingjing Meng\u003csup\u003e \u003c/sup\u003e,et,al.Prevalence and diagnostic value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome in Chinese patients. Front Immunol. 2023 Apr 12:14:1107510. doi: 10.3389/fimmu.2023.1107510. eCollection 2023.\u003c/li\u003e\n\u003cli\u003eSiting Li , Jiulang Zhao , Yina Bai ,et,al.Profile and clinical relevance of non-criteria antiphospholipid antibodies in patients diagnosed with or highly suspected of APS. Rheumatology (Oxford). 2024 Mar 1;63(3):891-900. doi: 10.1093/rheumatology/kead303.\u003c/li\u003e\n\u003cli\u003eTamihiro Kawakami , Ayaka Kikuchi , Chie Miyabe , et,al.Relationship between lysosomal-associated membrane protein-2 and anti-phosphatidylserine/prothrombin complex antibody in the pathogenesis of cutaneous vasculitis. Clin Exp Rheumatol. 2020 Mar-Apr;38 Suppl 124(2):161-165. Epub 2020 Jan 27.\u003c/li\u003e\n\u003cli\u003eYuncong Zhang , Yang Su , Han Guo , et, al.Anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) increase the risk for thrombosis based on lupus anticoagulant positivity. Clin Biochem. 2023 Feb:112:17-23. doi: 10.1016/j.clinbiochem.2022.12.007. Epub 2022 Dec 16.\u003c/li\u003e\n\u003cli\u003ePoon CS, Chang JK, Swarnkar A, Johnson MH, Wasenko J. Radiologic diagnosis of cerebral venous thrombosis: pictorial review. AJR Am J Roentgenol, 2007, 189(6 Suppl):64⁃75.\u003c/li\u003e\n\u003cli\u003eSavino Sciascia, Giovanni Sanna, Veronica Murru,et,al.Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review. Thromb Haemost. 2014 Feb;111(2):354-64. doi: 10.1160/TH13-06-0509.Epub 2013 Oct 31.\u003c/li\u003e\n\u003cli\u003eJanjua N. Cerebral angiography and venography for evaluation of cerebral venous thrombosis. J Pak Med Assoc, 2006, 56:527⁃ 530.\u003c/li\u003e\n\u003cli\u003eShingo Sakamoto , Koichi Akutsu, Kayoko Kawase,et,al.Simultaneous presentations of deep vein thrombosis and cerebral sinus thrombosis in a case of primary antiphospholipid syndrome, Angiology. 2008;59(6):765-8. doi: 10.1177/0003319707309310.Epub 2008 Apr 2.\u003c/li\u003e\n\u003cli\u003eDeepa J. Arachchillage1, Sean Platton, Kieron Hickey, et, at. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2024;205:855\u0026ndash;880. DOI: 10.1111/bjh.19635.\u003c/li\u003e\n\u003cli\u003eKatrien M. J. Devreese,Maria Laura Bertolaccini,D. Ware Branch, et, al. An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. J Thromb Haemost. 2025;23:731\u0026ndash;744.\u003c/li\u003e\n\u003cli\u003eTingting Liu , Jieyu Gu , Liyan Wan , et,al.\u0026quot;Non-criteria\u0026quot; antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort. Arthritis Res Ther. 2020 Feb 21;22(1):33. doi: 10.1186/s13075-020-2131-4.\u003c/li\u003e\n\u003cli\u003eRui Gao , Lang Qin，Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues[Article in Chinese]\u003cstrong\u003e.\u003c/strong\u003e Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 May 20;55(3):513-520.doi: 10.12182/20240560104.\u003c/li\u003e\n\u003cli\u003eWoller SC, Stevens SM, Kaplan D, et al. Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphos pholipid syndrome: a randomized trial[J]. Blood Adv, 2022, 6(6): 1661-1670. DOI: 10.1182/bloodadvances.2021005808.\u003c/li\u003e\n\u003cli\u003eTektonidou MG, Andreoli L, Limper M, et al. EULAR recom mendations for the management of antiphospholipid syn drome in adults[J]. Ann Rheum Dis, 2019, 78(10): 1296-1304. DOI: 10.1136/annrheumdis-2019-215213. \u003c/li\u003e\n\u003cli\u003eCao XY, Li BM, Li S, Wang J, Ma YD, Liu XF, Liang YP, Ge AL, Zhang AL. Angiography and clinical analysis of intracranial venous sinus in jugular foramen. Zhongguo Xian Dai Shen Jing Ji Bing Za Zhi, 2013, 13:222⁃225.\u003c/li\u003e\n\u003cli\u003eDashti SR, Hu YC, Yao T, Fiorella D, Mitha AP, Albuquerque FC, McDougall CG. Mechanical thrombectomy as first ⁃ line treatment for venous sinus thrombosis: technical considerations and preliminary results using the AngioJet device. J Neurointerv Surg, 2013, 5:49⁃53. \u003c/li\u003e\n\u003cli\u003eDe Bruijn SF, Stam J. Randomized, placebo controlled trial of anticoagulant treatment with low molecular weight heparin for cerebral sinus thrombosis. Stroke, 1999, 30:484⁃488.\u003c/li\u003e\n\u003cli\u003eStam J. Sinus thrombosis should be treated with anticoagulation. Arch Neurol, 2008, 6:984⁃985.\u003c/li\u003e\n\u003cli\u003eCoutinho J, de Bruijn SF, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev, 2011, 10(8):CD002005.\u003c/li\u003e\n\u003cli\u003eMehraein S, Schmidtke K, Villringer A, Valdueza JM, Masuhr F. Heparin treatment in cerebral sinus and venous thrombosis: patients at risk of fatal outcome. Cerebrovasc Dis, 2003, 15:17⁃ 21.\u003c/li\u003e\n\u003cli\u003eSaposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke, 2011, 42:1158⁃1192.\u003c/li\u003e\n\u003cli\u003eEinh\u0026auml;upl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, Masuhr F; European Federation of Neurological Societies. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol, 2010, 17: 1229⁃1235.\u003c/li\u003e\n\u003cli\u003eAtalay Doğru , Yunus Ugan , Mehmet Şahin,et,al. Catastrophic antiphospholipid syndrome treated with rituximab: A case report. Eur J Rheumatol. 2017 Jun;4(2):145-147. doi: 10.5152/eurjrheum.2017.160073. Epub 2017 Jun 1.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Antiphospholipid syndrome, Cerebral venous sinus thrombosis, aPI-IgM, aPS/PT-IgM, Intracranial venous sinus thrombectomy, Anticoagulation","lastPublishedDoi":"10.21203/rs.3.rs-7529173/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7529173/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAntiphospholipid syndrome (APS) is a systemic autoimmune disorder that causes thrombotic events. APS rarely leads to cerebral venous sinus thrombosis (CVST), and it is even more uncommon for non-criteria antiphospholipid antibodies (aPI, aPS/PT-IgM) to contribute to CVST.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e\u003cp\u003eA 32-year-old male patient was admitted to the hospital with a chief complaint of \"headache for five days and limb convulsions for one hour.\" CT revealed a subarachnoid hemorrhage and a high-density shadow in the right transverse sinus area. CTV and DSA demonstrated a filling defect in the right internal jugular vein, right sigmoid sinus, right transverse sinus, straight sinus, and superior sagittal sinus. Following repeated thrombectomy, venous sinus imaging showed improvement after the removal of a large thrombus. The patient received sequential anticoagulant therapy with low-molecular-weight heparin and warfarin, dehydration therapy with mannitol, nimodipine for cerebral vasospasm prevention, levetiracetam for seizure management, and antibiotics. During treatment, the patient experienced swelling in the left upper limb at the site of an indwelling needle infusion. B-mode ultrasound revealed venous thrombosis in the left axillary and basilic veins. Laboratory tests showed an antinuclear antibody (ANA) titer of 1:100, and positivity for anti-SS-A antibodies. However, a labial gland biopsy revealed only a small number of lymphocytes, ruling out Sj\u0026ouml;gren\u0026rsquo;s syndrome. Genetic testing for folate metabolism showed mild abnormalities. The antiphospholipid antibody panel indicated positivity for anti-phosphatidylinositol antibody-IgM (aPI-IgM) and an elevated level of anti-phosphatidylserine/prothrombin complex antibody-IgM (aPS/PT-IgM) at 93.44 ng/mL (normal range: 0\u0026ndash;75 ng/mL). Bone marrow cytology was normal. The diagnosis was confirmed as cerebral venous sinus thrombosis due to APS. Four months later, follow-up CTV showed complete resolution of the thrombosis, but the antiphospholipid antibody panel remained positive for aPS/PT-IgM and anti-phosphatidylethanolamine antibody (aPE).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eNon-criteria antiphospholipid antibodies, particularly aPI-IgM and aPS/PT-IgM, can contribute to CVST. Vitamin K antagonists (VKAs) are the preferred anticoagulants, and mechanical thrombectomy should be considered in severe cases. The presence of aPS/PT-IgM may be closely associated with CVST and could serve as a potential molecular marker for APS.\u003c/p\u003e","manuscriptTitle":"Severe Cerebral Venous Sinus Thrombosis and Deep Vein Thrombosis Induced by Non-Criteria aPI and aPS/PT Positive Antiphospholipid Antibodies: A Case Report and Mini Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-13 07:54:53","doi":"10.21203/rs.3.rs-7529173/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-11T15:09:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-08T11:14:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-23T15:20:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-20T07:54:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-12T16:32:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-11T20:24:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"104015351903892045160442625484752852514","date":"2025-11-11T13:40:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152383849738541375797132233379144071805","date":"2025-11-09T07:22:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"106583094622006704436165963079247484424","date":"2025-11-08T08:53:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236624104801733499396218609923112634797","date":"2025-11-08T04:42:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260750552962375624986867502883401453039","date":"2025-11-05T17:00:03+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-31T16:44:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-29T18:23:53+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-09T20:58:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-08T09:51:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2025-10-08T09:48:23+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":"fa297ec9-6d3d-41ac-8f3a-7b6d506289d6","owner":[],"postedDate":"November 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-03T17:38:03+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-13 07:54:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7529173","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7529173","identity":"rs-7529173","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}