Successful course of pregnancy and childbirth despite the diagnosis of congenital thrombotic thrombocytopenic purpura in the pregnant woman

Successful course of pregnancy and childbirth despite the diagnosis of congenital thrombotic thrombocytopenic purpura in the pregnant woman | 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 Successful course of pregnancy and childbirth despite the diagnosis of congenital thrombotic thrombocytopenic purpura in the pregnant woman Beata Blajer-Olszewska, Katarzyna Kalandyk-Osinko, Agnieszka Kopacz, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9483019/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Although cTTP results from a congenital mutation of the ADAMTS13 gene, in some cases the manifestation of the disease depends on an additional triggering factor, and the diagnosis is made in adulthood. Case presentation We present the case of a 30-year-old woman with a history of ischemic strokes and one miscarriage, in whom at the 24th week of her second pregnancy, cTTP was diagnosed as a result of extensive hemolytic anemia diagnostics. After a complicated initial treatment using FFP, replacement therapy with recombinant ADAMTS13 was applied. On the 37th day of treatment, due to the diagnosis of preeclampsia, the pregnancy was terminated by cesarean section without complications. Conclusions Despite the diagnosis of a life-threatening disease for both the mother and fetus, the applied management allowed the pregnancy to be successfully brought to term, resulting in the birth of a healthy child and an uncomplicated postpartum course. congenital thrombotic thrombocytopenic purpura pregnancy recombinant ADAMTS13 Figures Figure 1 Figure 2 Figure 3 Background Thrombotic thrombocytopenic purpura (TTP) refers to thrombotic microangiopathy (TMA), which is an ultra-rare disease. The triad of thrombocytopenia, direct antiglobulin test (DAT)-negative hemolytic anemia, and ischemic anemia may occur, and the etiology is assumed to be generalized thrombosis of arterioles and capillaries [ 1 ]. Based on etiopathogenesis, TTP is divided into congenital TTP (cTTP), known as Upshaw-Schulman syndrome, caused by a mutation in the gene encoding a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), and acquired, immune-mediated TTP (iTTP), which results from autoantibodies blocking ADAMTS13 function. Within iTTP, a distinction is made between a primary form, which is not triggered by any identified triggering factor, and a secondary form, the etiology of which is highly diverse. These may include clinical conditions that increase von Willebrand factor (vWF) activity or decrease the body's immunity (e.g., inflammation, infections, pregnancy, cancer, connective tissue diseases), as well as medications [ 1 ]. The incidence of cTTP is not precisely known, but it is estimated that the disease occurs at a rate of 0.5–2/million inhabitants and in adults accounts for < 5% of all TTP cases [ 2 ]. iTTP is diagnosed at a rate of 2–6 cases/million inhabitants/year [ 3 ]. The underlying cause of TTP is a congenital or acquired deficiency of the plasma metalloproteinase ADAMTS13, which degrades ultra-large von Willebrand factor multimers (UL-VWF). This deficiency leads to the clinical manifestations of the disease. UL-VWF binds to platelets, forming fibrin-poor clots that block blood flow in capillaries and small arterioles, particularly in the brain, heart, and kidneys. Incoming erythrocytes, encountering or squeezing through the clots, fragment into schistocytes, also known as fragmentocytes. Platelet entrapment in the resulting clots leads to thrombocytopenia [ 4 ]. cTTP develops in homozygotes or heterozygotes with pathogenic variants of both alleles of the ADAMTS13 gene. The timing of clinical manifestations of the disease depends on the type of ADAMTS13 gene mutation. Most of the approximately 150 detected mutations manifest in early childhood, but some may not become apparent until adulthood, usually after an additional stimulus, such as pregnancy. Although cTTP is very rare in adults, at least half of all cTTP cases begin in adulthood and are often associated with pregnancy [ 5 ]. Among all TTP cases diagnosed during pregnancy, cTTP accounts for 33%, and in the first pregnancy, up to 50%. cTTP manifests already in the first pregnancy, most often in the second half. Diagnosis of cTTP during pregnancy is a serious problem associated with a high, approximately 40%, risk of fetal loss, but this is estimated primarily based on retrospective studies involving a large number of women misdiagnosed and treated too late for TTP [ 1 ]. Similarly, pregnancy in a woman diagnosed with cTTP should be considered extremely high-risk, as complications of cTTP can lead to fetal and/or maternal death. Therefore, cTTP during pregnancy requires treatment to maintain a normal platelet count. Prevention of acute episodes is the primary goal of cTTP prophylaxis, which involves the administration of recombinant ADAMTS13 (rADAMTS13) or, if unavailable, fresh frozen plasma (FFP). If both rADAMTS13 and plasma are available, rADAMTS13 is recommended over plasma due to improved outcomes, significantly greater ease of administration (it can be done in minutes at home versus several hours in an infusion center), and a lower risk of adverse events (plasma carries a risk of transfusion reactions and infections) [ 6 ]. Case presentation A 30-year-old woman, 24 weeks into her second pregnancy, was hospitalized at the Pregnancy Pathology Department due to abnormalities in her peripheral blood counts. She had a history of five ischemic strokes (the last one was eight years ago), following which she developed post-stroke epilepsy, currently well-controlled with levetiracetam. While investigating the cause of the strokes, congenital thrombophilia, antiphospholipid syndrome, and congenital heart defects were excluded. Ultimately, a mildly elevated factor VIII level was identified as the cause, and antiplatelet and anticoagulant therapy with clopidogrel and apixaban was initiated. Since then, no further thrombotic episodes have been observed. The patient's first pregnancy ended eight months ago with a miscarriage at 11 weeks, when an episode of transient mild thrombocytopenia was observed. Since the beginning of the current pregnancy, the patient has been treated with antiplatelet acetylsalicylic acid and anticoagulant therapy with low molecular weight heparin (LMWH) at a dose of 2x60 mg sc. Blood test results remained normal, with no signs of active hemolysis, anemia, or thrombocytopenia. During her stay at the Pregnancy Pathology Department, mild DAT-negative hemolytic anemia (Hgb 10.5 g/dL) with the presence of schistocytes on a microscopic peripheral blood smear and profound thrombocytopenia (22 G/L) were observed. The patient underwent hematological, cardiological, and neurologic consultations. New neurological symptoms, signs of damage to other organs, and active inflammation were ruled out. The fetus was in satisfactory condition. Acetylsalicylic acid and LMWH were discontinued, glucocorticosteroid therapy (prednisone at a dose of initially 0.5 mg/kg, then 1 mg/kg) and FFP transfusions were initiated. Urgent testing for ADAMTS13 activity and for its antibodies was recommended, and the patient was simultaneously transferred to the Hematology Department. In the first 24 hours after starting FFP substitution, severe shortness of breath and signs of full-blown pulmonary edema appeared during the night hours. Standard procedures were applied, resulting in gradual improvement. In the morning hours, the patient developed a fever, and auscultatory signs of left-sided pneumonia appeared. Broad-spectrum antibiotic therapy was initiated. Due to the episode of volume overload-related pulmonary edema and inflammatory changes in the lung, continuation of adequate FFP administration proved impossible. Autoimmune diseases, paroxysmal nocturnal hemoglobinuria (PNH), and antiphospholipid syndrome (APS) were ruled out in the patient. Demonstration of reduced ADAMTS13 activity (2.8%) in the absence of an inhibitor allowed for the diagnosis of the cTTP. Due to the inability to continue FFP transfusions, the only possible treatment was substitution with rADAMTS13 (Adzynma). Due to the life-threatening condition, the drug was procured as a rescue at the hospital's own expense, while at the same time an application was submitted to the National Health Fund for reimbursement under the emergency access to drug therapy. According to the recommendations for management in an acute episode of TTP, treatment was started with a dose of 40 IU/kg (3000 IU) on the first day and 20 IU/kg (1500 IU) on the second day of treatment, and then a dose of 15 IU/kg/day (1000 IU) was administered (the course of rADAMTS13 dosing is shown in Fig. 1 ) under the control of platelet count, hemolysis markers, and periodic measurements of ADAMTS13 activity (ADAMTS13 activity measurements are shown in Fig. 2 ). From the 2nd day of treatment, a systematic increase in platelet count was observed, and full normalization (PLT > 150 G/l) was noted on the 6th day of treatment (the results of PLT count measurements are shown in Fig. 3 ). After the diagnosis of cTTP was established, the doses of glucocorticosteroids were gradually reduced, while low-molecular-weight heparin (LMWH), Clexane 60 mg s.c. and acetylsalicylic acid at a dose of 75 mg/day were reinstated. During hospitalization, the patient was diagnosed with de novo arterial hypertension, for which amlodipine and metoprolol were added to the treatment. Additionally, progressive proteinuria was observed (initially 1 g/day, on the day of discharge 3.3 g/day). The patient was systematically consulted gynecologically: a physical examination assessing the condition and maturity of the cervix was performed, vaginal bacterial swabs were taken, laboratory tests were conducted according to standards applicable during pregnancy, and fetal well-being was also assessed. Fetal weight gain was monitored using percentile charts available in the FMF Barcelona calculator. Blood flow in the umbilical artery, uterine arteries, middle cerebral artery, and ductus venosus was assessed. The flow value through the middle cerebral artery was converted to MoM values using the MCA Peak Systolic Velocity Calculator on Perinatology.com to exclude fetal anemia. After 22 days of hospitalization, the patient was discharged from the Hematology Department to home with a recommendation for strict outpatient follow-up. On the day of discharge, the platelet count was 130 G/l (at this stage, a component of pregnancy-related thrombocytopenia could already have joined), without indicators of active hemolysis. Due to the overall clinical picture and the lack of precise guidelines regarding rADAMTS13 dosing in pregnant patients, it was decided to administer maintenance doses of 1,500-2,000 IU once a week. The results of follow-up peripheral blood counts performed after discharge remained normal. On the 33rd day of treatment, the patient was readmitted to the Pregnancy Pathology Department for the assessment of fetal well-being and the planned administration of glucocorticosteroids to stimulate fetal lungs in case of the need for an early termination of pregnancy. On the day of admission, the patient's condition was stable, with no abnormalities in the gynecological assessment, Hgb 11.9 g/dl, platelets 146 G/l, LDH 360 (N: 120–246) IU/l, but on the fourth day of hospitalization, a decrease in platelet count to 67 G/l was observed again, along with increased LDH, bilirubin, AST, and ALT, decreased haptoglobin, rising proteinuria (up to 8.8 g/day), and arterial hypertension – laboratory and clinical signs of preeclampsia. The procedure for an acute TTP episode was implemented again: rADAMTS13 was administered at a dose of 3000 IU, resulting the following day in an increase in platelet count to 89,000/µl. The CTG recording showed an acceleration pattern and short-term variability (STV) appropriate for gestational age. Ultrasound examination revealed normal flow through the umbilical artery and the ductus venosus, with present flow during diastole; periodically, signs of circulatory centralization were observed in the evaluation of blood flow through the umbilical artery and the middle cerebral artery. Preeclampsia was diagnosed; therefore, a prompt pregnancy termination by cesarean section was planned and performed on day 37 of rADAMTS13 treatment, without observing complications. The amniotic fluid was noted to be scant and greenish, and the placenta had very numerous, small microthrombi. In the histopathological examination of the placenta, congestion of the vessels of the umbilical cord and placental villi, chorangiosis, chorangiomatosis, and ischemic infarctions of the placenta, as well as fibrinous inflammation of the fetal membranes, were found, which confirmed the etiopathogenesis of the disease and consequently could have led to placental insufficiency and intrauterine fetal death. This fact emphasizes the importance of monitoring fetal well-being through serial flow measurements in ultrasound examination. The features of circulatory centralization resulting from histopathological changes in the placenta were the reason for the decision to perform a cesarean section. The day after delivery, ADAMTS13 activity was 93%, and in the newborn, who was in good condition, it was 43%. In the patient, daily rADAMTS13 substitution was continued in the following days until platelet counts stabilized, and for the remainder of the postpartum period, rADAMTS13 dosing was set at 2000 IU once a week, under the control of blood count results and periodic measurement of ADAMTS13 activity. Subsequently, treatment was continued according to the Summary of Product Characteristics (SPC) within the drug program made available from the 56th day of the patient’s treatment. The patient was discharged in good general condition on the 10th day after delivery, additionally with the recommendation to continue LMWH therapy at a dose of 60 mg sc throughout the postpartum period, which proceeded without complications. Discussion and Conclusions Pregnancy and the postpartum period are known risk factors for the development of TMA syndromes. Clinical symptoms of TTP beginning in pregnancy may overlap with other TMA more commonly occurring during pregnancy, such as preeclampsia, especially the pregnancy-specific HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet count) or TMA resulting from disseminated intravascular coagulation, antiphospholipid syndrome, or hemolytic-uremic syndrome (not specific to pregnancy). Therefore, differential diagnosis of TTP from other TMA starting in pregnancy remains very difficult. Neurological symptoms, including headache, migraine, visual disturbances, transient ischemic attacks, and proteinuria, have been described in cTTP in pregnant women. However, there may also be symptoms that could suggest a diagnosis of other pregnancy-related TMAs, such as preeclampsia, proteinuria, and kidney damage [ 7 ]. Pregnancy-onset TMA in rare cases corresponds to TTP, with an overall incidence of about 1 in 200,000 pregnancies, accounting for approximately 10% of all TTP cases. The specificity of TTP in pregnancy is the relatively high frequency (from 24% to 66%) of the late-onset cTTP, which otherwise occurs extremely rarely in adults. In a 20-year (2000–2020) analysis of TTP incidence in France, cTTP was diagnosed in 29 of 108 (26.9%) of all TTP cases recognized during pregnancy or postpartum [ 8 ], whereas in a 4-year (2009–2014) British analysis, cTTP was diagnosed in 23 of 35 (66%) such cases [ 7 ]. In patients in whom cTTP was diagnosed during pregnancy, similarly to our patient, a history of ischemic strokes and miscarriages has been reported [ 5 ]. Therefore, in young individuals who experience ischemic episodes and miscarriages, it is justified to deepen the diagnostic process for TTP, even when basic test results are normal. Close cooperation between gynecologists-obstetricians and hematologists is very important, as is a strong diagnostic background and the possibility of conducting a hematology consultation at a reference center, which enables the fastest possible diagnosis and implementation of appropriate treatment. Currently, in the treatment of cTTP in children and adult patients, enzyme replacement therapy using rADAMTS13 is used. There are no precise guidelines for its use in pregnant patients. The limiting factor of the work is the lack of confirmation of the presence of homozygous or compound heterozygous variants in the ADAMTS13 gene in the genetic study. More than 150 genetic variants of ADAMTS13 have been described, with the most common being the variant in exon 24 R1060W (rs142572218), associated with a later onset of the disease [ 4 ]. The diagnosis of cTTP was established based on the finding of low ADAMTS13 activity and the absence of antibodies. The history of ischemic episodes occurring over many years and a previous miscarriage in a patient in whom no antibodies were detected supports the diagnosis of cTTP in her. It should be noted, however, that among cases of TTP starting during pregnancy, some may represent acquired, non-immunological TTP of unidentified pathophysiology (uTTP). In uTTP, similar to cTTP, a reduced ADAMTS13 concentration is accompanied by the absence of antibodies. In the course of uTTP, a very low risk of disease recurrence, independent of subsequent pregnancies, is characteristic. The pathomechanism underlying uTTP is unknown, but the possibility of a physiological mechanism related to the prolonged occurrence of high VWF levels during pregnancy is considered, or, according to another hypothesis, the involvement of hormonal changes occurring in pregnancy that lead to ADAMTS13 degradation. In terms of mechanisms leading to severe ADAMTS13 deficiency, obstetric uTTP therefore constitutes a complex entity, with many unresolved questions [ 8 ]. Our report presents the procedure that led to the diagnosis of the congenital form of TTP in an adult patient - a pregnant woman. Importantly, thanks to the rapid establishment of the diagnosis and the implementation of optimal treatment- enzyme replacement therapy with rADAMTS13, it was possible to successfully carry the pregnancy to a successful outcome, give birth to a healthy child, and have an uncomplicated postpartum course. Abbreviations ADAMTS13 - a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 APS - antiphospholipid syndrome cTTP - congenital TTP DAT - direct antiglobulin test FFP - fresh frozen plasma iTTP - immune-mediated TTP LMWH - low molecular weight heparin PNH - paroxysmal nocturnal hemoglobinuria rADAMTS13 - recombinant ADAMTS13 SPC - summary of product characteristics TMA - thrombotic microangiopathy TTP - thrombotic thrombocytopenic purpura UL-VWF - ultra-large von Willebrand factor multimers uTTP - unidentified pathophysiology vWF - von Willebrand factor Declarations Ethics approval and consent to participate All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent for publication Authors obtained patient’s informed consent for publication. Competing interests The authors declare that they have no competing interests Funding This work was supported by Uniwersytet Rzeszowski. Author Contribution BBO: substantial contributions to the conception, acquisition, analysis and interpretation of data and drafting the work; KKO: substantial contributions to the acquisition, analysis and interpretation of data and drafting the work; AK: substantial contributions to acquisition, analysis and interpretation of data; SK: substantial contributions to the acquisition of data; AWP: substantial contributions to the acquisition of data; DO: substantial contributions to the acquisition of data; JZ: substantial contributions to analysis and interpretation of data; TI: substantial contributions to analysis and interpretation of data; TK: substantial contributions to the acquisition, analysis and interpretation of data; MM: drafting the work and reviewing it critically for important intellectual content, final approval for all aspects of the version of the work to be published in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript. Acknowledgments Not applicable. Data Availability The datasets used and analysed during the current study are available from the corresponding author on reasonable request. References Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836–46. 10.1182/blood-2016-10-709857 . Kremer Hovinga JA, George JN. Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med. 2019;381(17):1653–62. 10.1056/NEJMra1813013 . Pishko AM, Li A, Cuker A. Immune Thrombotic Thrombocytopenic Purpura: A Review. JAMA. 2025;334(6):517–29. 10.1001/jama.2025.3807 . Scully M, Rayment R, Clark A, Westwood JP, Cranfield T, Gooding R, Bagot CN, Taylor A, Sankar V, Gale D, Dutt T, McIntyre J, Lester W, BSH Committee. A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies. Br J Haematol. 2023;203(4):546–63. 10.1111/bjh.19026 . Tenison E, Asif A, Sheridan M. Congenital thrombotic thrombocytopenic purpura presenting in adulthood with recurrent cerebrovascular events. BMJ Case Rep. 2019;12(10):e229481. 10.1136/bcr-2019-229481 . Taylor A, Scully M. Modern management of congenital thrombotic thrombocytopenic purpura (cTTP). Hematol Am Soc Hematol Educ Program. 2025;2025(1):628–35. 10.1182/hematology.2025000759 . Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS, Clark A, Creagh D, Rayment R, Mcdonald V, Roy A, Evans G, McGuckin S, Ni Ainle F, Maclean R, Lester W, Nash M, Scott R, O Brien P. collaborators of the UK TTP Registry. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014;124(2):211–9. 10.1182/blood-2014-02-553131 . Béranger N, Coppo P, Tsatsaris V, Boisseau P, Provôt F, Delmas Y, Poullin P, Vanhoorelbeke K, Veyradier A, Joly BS. Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience. Blood Adv. 2024;8(1):183–93. 10.1182/bloodadvances.2023011972 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 29 Apr, 2026 Editor assigned by journal 23 Apr, 2026 Submission checks completed at journal 23 Apr, 2026 First submitted to journal 21 Apr, 2026 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. 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Chopin University Clinical Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomasz","middleName":"","lastName":"Kluz","suffix":""},{"id":631999643,"identity":"e73c8a98-6879-4313-8f66-e5ceb8dfbd88","order_by":9,"name":"Mirosław Markiewicz","email":"data:image/png;base64,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","orcid":"","institution":"Rzeszów University","correspondingAuthor":true,"prefix":"","firstName":"Mirosław","middleName":"","lastName":"Markiewicz","suffix":""}],"badges":[],"createdAt":"2026-04-21 10:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9483019/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9483019/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108946352,"identity":"c0357943-ed4f-469a-9a56-c511532e3f41","added_by":"auto","created_at":"2026-05-11 06:22:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13073,"visible":true,"origin":"","legend":"\u003cp\u003eDose of rADAMTS13 during cTTP treatment\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9483019/v1/ce1d00dd98072a79c7015a73.png"},{"id":108946350,"identity":"48b58a43-e124-4b4a-84de-70d14df6735e","added_by":"auto","created_at":"2026-05-11 06:22:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11708,"visible":true,"origin":"","legend":"\u003cp\u003eADAMTS13 activity during cTTP treatment\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9483019/v1/886b45e48dc3665c58a44dfa.png"},{"id":108946351,"identity":"b911d563-a181-486d-a95f-a28c0c4670d3","added_by":"auto","created_at":"2026-05-11 06:22:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":15195,"visible":true,"origin":"","legend":"\u003cp\u003ePlatelet count during cTTP treatment\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9483019/v1/7d4867106735c4812c4ac744.png"},{"id":108977573,"identity":"fea9613f-0aff-47f5-ba7d-9d1d8460575c","added_by":"auto","created_at":"2026-05-11 11:32:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":188680,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9483019/v1/167ae215-32a7-4cc2-83ef-3179ff5e0a5f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Successful course of pregnancy and childbirth despite the diagnosis of congenital thrombotic thrombocytopenic purpura in the pregnant woman","fulltext":[{"header":"Background","content":"\u003cp\u003eThrombotic thrombocytopenic purpura (TTP) refers to thrombotic microangiopathy (TMA), which is an ultra-rare disease. The triad of thrombocytopenia, direct antiglobulin test (DAT)-negative hemolytic anemia, and ischemic anemia may occur, and the etiology is assumed to be generalized thrombosis of arterioles and capillaries [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on etiopathogenesis, TTP is divided into congenital TTP (cTTP), known as Upshaw-Schulman syndrome, caused by a mutation in the gene encoding a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), and acquired, immune-mediated TTP (iTTP), which results from autoantibodies blocking ADAMTS13 function. Within iTTP, a distinction is made between a primary form, which is not triggered by any identified triggering factor, and a secondary form, the etiology of which is highly diverse. These may include clinical conditions that increase von Willebrand factor (vWF) activity or decrease the body's immunity (e.g., inflammation, infections, pregnancy, cancer, connective tissue diseases), as well as medications [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe incidence of cTTP is not precisely known, but it is estimated that the disease occurs at a rate of 0.5\u0026ndash;2/million inhabitants and in adults accounts for \u0026lt;\u0026thinsp;5% of all TTP cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. iTTP is diagnosed at a rate of 2\u0026ndash;6 cases/million inhabitants/year [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe underlying cause of TTP is a congenital or acquired deficiency of the plasma metalloproteinase ADAMTS13, which degrades ultra-large von Willebrand factor multimers (UL-VWF). This deficiency leads to the clinical manifestations of the disease. UL-VWF binds to platelets, forming fibrin-poor clots that block blood flow in capillaries and small arterioles, particularly in the brain, heart, and kidneys. Incoming erythrocytes, encountering or squeezing through the clots, fragment into schistocytes, also known as fragmentocytes. Platelet entrapment in the resulting clots leads to thrombocytopenia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ecTTP develops in homozygotes or heterozygotes with pathogenic variants of both alleles of the ADAMTS13 gene. The timing of clinical manifestations of the disease depends on the type of ADAMTS13 gene mutation. Most of the approximately 150 detected mutations manifest in early childhood, but some may not become apparent until adulthood, usually after an additional stimulus, such as pregnancy. Although cTTP is very rare in adults, at least half of all cTTP cases begin in adulthood and are often associated with pregnancy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among all TTP cases diagnosed during pregnancy, cTTP accounts for 33%, and in the first pregnancy, up to 50%. cTTP manifests already in the first pregnancy, most often in the second half. Diagnosis of cTTP during pregnancy is a serious problem associated with a high, approximately 40%, risk of fetal loss, but this is estimated primarily based on retrospective studies involving a large number of women misdiagnosed and treated too late for TTP [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Similarly, pregnancy in a woman diagnosed with cTTP should be considered extremely high-risk, as complications of cTTP can lead to fetal and/or maternal death. Therefore, cTTP during pregnancy requires treatment to maintain a normal platelet count.\u003c/p\u003e \u003cp\u003ePrevention of acute episodes is the primary goal of cTTP prophylaxis, which involves the administration of recombinant ADAMTS13 (rADAMTS13) or, if unavailable, fresh frozen plasma (FFP). If both rADAMTS13 and plasma are available, rADAMTS13 is recommended over plasma due to improved outcomes, significantly greater ease of administration (it can be done in minutes at home versus several hours in an infusion center), and a lower risk of adverse events (plasma carries a risk of transfusion reactions and infections) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 30-year-old woman, 24 weeks into her second pregnancy, was hospitalized at the Pregnancy Pathology Department due to abnormalities in her peripheral blood counts. She had a history of five ischemic strokes (the last one was eight years ago), following which she developed post-stroke epilepsy, currently well-controlled with levetiracetam. While investigating the cause of the strokes, congenital thrombophilia, antiphospholipid syndrome, and congenital heart defects were excluded. Ultimately, a mildly elevated factor VIII level was identified as the cause, and antiplatelet and anticoagulant therapy with clopidogrel and apixaban was initiated. Since then, no further thrombotic episodes have been observed. The patient's first pregnancy ended eight months ago with a miscarriage at 11 weeks, when an episode of transient mild thrombocytopenia was observed. Since the beginning of the current pregnancy, the patient has been treated with antiplatelet acetylsalicylic acid and anticoagulant therapy with low molecular weight heparin (LMWH) at a dose of 2x60 mg sc. Blood test results remained normal, with no signs of active hemolysis, anemia, or thrombocytopenia.\u003c/p\u003e \u003cp\u003eDuring her stay at the Pregnancy Pathology Department, mild DAT-negative hemolytic anemia (Hgb 10.5 g/dL) with the presence of schistocytes on a microscopic peripheral blood smear and profound thrombocytopenia (22 G/L) were observed. The patient underwent hematological, cardiological, and neurologic consultations. New neurological symptoms, signs of damage to other organs, and active inflammation were ruled out. The fetus was in satisfactory condition. Acetylsalicylic acid and LMWH were discontinued, glucocorticosteroid therapy (prednisone at a dose of initially 0.5 mg/kg, then 1 mg/kg) and FFP transfusions were initiated. Urgent testing for ADAMTS13 activity and for its antibodies was recommended, and the patient was simultaneously transferred to the Hematology Department.\u003c/p\u003e \u003cp\u003eIn the first 24 hours after starting FFP substitution, severe shortness of breath and signs of full-blown pulmonary edema appeared during the night hours. Standard procedures were applied, resulting in gradual improvement. In the morning hours, the patient developed a fever, and auscultatory signs of left-sided pneumonia appeared. Broad-spectrum antibiotic therapy was initiated. Due to the episode of volume overload-related pulmonary edema and inflammatory changes in the lung, continuation of adequate FFP administration proved impossible. Autoimmune diseases, paroxysmal nocturnal hemoglobinuria (PNH), and antiphospholipid syndrome (APS) were ruled out in the patient. Demonstration of reduced ADAMTS13 activity (2.8%) in the absence of an inhibitor allowed for the diagnosis of the cTTP. Due to the inability to continue FFP transfusions, the only possible treatment was substitution with rADAMTS13 (Adzynma). Due to the life-threatening condition, the drug was procured as a rescue at the hospital's own expense, while at the same time an application was submitted to the National Health Fund for reimbursement under the emergency access to drug therapy. According to the recommendations for management in an acute episode of TTP, treatment was started with a dose of 40 IU/kg (3000 IU) on the first day and 20 IU/kg (1500 IU) on the second day of treatment, and then a dose of 15 IU/kg/day (1000 IU) was administered (the course of rADAMTS13 dosing is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) under the control of platelet count, hemolysis markers, and periodic measurements of ADAMTS13 activity (ADAMTS13 activity measurements are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFrom the 2nd day of treatment, a systematic increase in platelet count was observed, and full normalization (PLT\u0026thinsp;\u0026gt;\u0026thinsp;150 G/l) was noted on the 6th day of treatment (the results of PLT count measurements are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter the diagnosis of cTTP was established, the doses of glucocorticosteroids were gradually reduced, while low-molecular-weight heparin (LMWH), Clexane 60 mg s.c. and acetylsalicylic acid at a dose of 75 mg/day were reinstated. During hospitalization, the patient was diagnosed with de novo arterial hypertension, for which amlodipine and metoprolol were added to the treatment. Additionally, progressive proteinuria was observed (initially 1 g/day, on the day of discharge 3.3 g/day).\u003c/p\u003e \u003cp\u003eThe patient was systematically consulted gynecologically: a physical examination assessing the condition and maturity of the cervix was performed, vaginal bacterial swabs were taken, laboratory tests were conducted according to standards applicable during pregnancy, and fetal well-being was also assessed. Fetal weight gain was monitored using percentile charts available in the FMF Barcelona calculator. Blood flow in the umbilical artery, uterine arteries, middle cerebral artery, and ductus venosus was assessed. The flow value through the middle cerebral artery was converted to MoM values using the MCA Peak Systolic Velocity Calculator on Perinatology.com to exclude fetal anemia.\u003c/p\u003e \u003cp\u003eAfter 22 days of hospitalization, the patient was discharged from the Hematology Department to home with a recommendation for strict outpatient follow-up. On the day of discharge, the platelet count was 130 G/l (at this stage, a component of pregnancy-related thrombocytopenia could already have joined), without indicators of active hemolysis. Due to the overall clinical picture and the lack of precise guidelines regarding rADAMTS13 dosing in pregnant patients, it was decided to administer maintenance doses of 1,500-2,000 IU once a week. The results of follow-up peripheral blood counts performed after discharge remained normal.\u003c/p\u003e \u003cp\u003eOn the 33rd day of treatment, the patient was readmitted to the Pregnancy Pathology Department for the assessment of fetal well-being and the planned administration of glucocorticosteroids to stimulate fetal lungs in case of the need for an early termination of pregnancy. On the day of admission, the patient's condition was stable, with no abnormalities in the gynecological assessment, Hgb 11.9 g/dl, platelets 146 G/l, LDH 360 (N: 120\u0026ndash;246) IU/l, but on the fourth day of hospitalization, a decrease in platelet count to 67 G/l was observed again, along with increased LDH, bilirubin, AST, and ALT, decreased haptoglobin, rising proteinuria (up to 8.8 g/day), and arterial hypertension \u0026ndash; laboratory and clinical signs of preeclampsia. The procedure for an acute TTP episode was implemented again: rADAMTS13 was administered at a dose of 3000 IU, resulting the following day in an increase in platelet count to 89,000/\u0026micro;l. The CTG recording showed an acceleration pattern and short-term variability (STV) appropriate for gestational age. Ultrasound examination revealed normal flow through the umbilical artery and the ductus venosus, with present flow during diastole; periodically, signs of circulatory centralization were observed in the evaluation of blood flow through the umbilical artery and the middle cerebral artery. Preeclampsia was diagnosed; therefore, a prompt pregnancy termination by cesarean section was planned and performed on day 37 of rADAMTS13 treatment, without observing complications. The amniotic fluid was noted to be scant and greenish, and the placenta had very numerous, small microthrombi. In the histopathological examination of the placenta, congestion of the vessels of the umbilical cord and placental villi, chorangiosis, chorangiomatosis, and ischemic infarctions of the placenta, as well as fibrinous inflammation of the fetal membranes, were found, which confirmed the etiopathogenesis of the disease and consequently could have led to placental insufficiency and intrauterine fetal death. This fact emphasizes the importance of monitoring fetal well-being through serial flow measurements in ultrasound examination. The features of circulatory centralization resulting from histopathological changes in the placenta were the reason for the decision to perform a cesarean section.\u003c/p\u003e \u003cp\u003eThe day after delivery, ADAMTS13 activity was 93%, and in the newborn, who was in good condition, it was 43%. In the patient, daily rADAMTS13 substitution was continued in the following days until platelet counts stabilized, and for the remainder of the postpartum period, rADAMTS13 dosing was set at 2000 IU once a week, under the control of blood count results and periodic measurement of ADAMTS13 activity. Subsequently, treatment was continued according to the Summary of Product Characteristics (SPC) within the drug program made available from the 56th day of the patient\u0026rsquo;s treatment. The patient was discharged in good general condition on the 10th day after delivery, additionally with the recommendation to continue LMWH therapy at a dose of 60 mg sc throughout the postpartum period, which proceeded without complications.\u003c/p\u003e"},{"header":"Discussion and Conclusions","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003ePregnancy and the postpartum period are known risk factors for the development of TMA syndromes. Clinical symptoms of TTP beginning in pregnancy may overlap with other TMA more commonly occurring during pregnancy, such as preeclampsia, especially the pregnancy-specific HELLP syndrome (hemolysis, elevated liver enzyme levels, and low platelet count) or TMA resulting from disseminated intravascular coagulation, antiphospholipid syndrome, or hemolytic-uremic syndrome (not specific to pregnancy). Therefore, differential diagnosis of TTP from other TMA starting in pregnancy remains very difficult. Neurological symptoms, including headache, migraine, visual disturbances, transient ischemic attacks, and proteinuria, have been described in cTTP in pregnant women. However, there may also be symptoms that could suggest a diagnosis of other pregnancy-related TMAs, such as preeclampsia, proteinuria, and kidney damage [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Pregnancy-onset TMA in rare cases corresponds to TTP, with an overall incidence of about 1 in 200,000 pregnancies, accounting for approximately 10% of all TTP cases. The specificity of TTP in pregnancy is the relatively high frequency (from 24% to 66%) of the late-onset cTTP, which otherwise occurs extremely rarely in adults. In a 20-year (2000\u0026ndash;2020) analysis of TTP incidence in France, cTTP was diagnosed in 29 of 108 (26.9%) of all TTP cases recognized during pregnancy or postpartum [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], whereas in a 4-year (2009\u0026ndash;2014) British analysis, cTTP was diagnosed in 23 of 35 (66%) such cases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn patients in whom cTTP was diagnosed during pregnancy, similarly to our patient, a history of ischemic strokes and miscarriages has been reported [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Therefore, in young individuals who experience ischemic episodes and miscarriages, it is justified to deepen the diagnostic process for TTP, even when basic test results are normal. Close cooperation between gynecologists-obstetricians and hematologists is very important, as is a strong diagnostic background and the possibility of conducting a hematology consultation at a reference center, which enables the fastest possible diagnosis and implementation of appropriate treatment. Currently, in the treatment of cTTP in children and adult patients, enzyme replacement therapy using rADAMTS13 is used. There are no precise guidelines for its use in pregnant patients.\u003c/p\u003e \u003cp\u003eThe limiting factor of the work is the lack of confirmation of the presence of homozygous or compound heterozygous variants in the ADAMTS13 gene in the genetic study. More than 150 genetic variants of ADAMTS13 have been described, with the most common being the variant in exon 24 R1060W (rs142572218), associated with a later onset of the disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The diagnosis of cTTP was established based on the finding of low ADAMTS13 activity and the absence of antibodies. The history of ischemic episodes occurring over many years and a previous miscarriage in a patient in whom no antibodies were detected supports the diagnosis of cTTP in her. It should be noted, however, that among cases of TTP starting during pregnancy, some may represent acquired, non-immunological TTP of unidentified pathophysiology (uTTP). In uTTP, similar to cTTP, a reduced ADAMTS13 concentration is accompanied by the absence of antibodies. In the course of uTTP, a very low risk of disease recurrence, independent of subsequent pregnancies, is characteristic. The pathomechanism underlying uTTP is unknown, but the possibility of a physiological mechanism related to the prolonged occurrence of high VWF levels during pregnancy is considered, or, according to another hypothesis, the involvement of hormonal changes occurring in pregnancy that lead to ADAMTS13 degradation. In terms of mechanisms leading to severe ADAMTS13 deficiency, obstetric uTTP therefore constitutes a complex entity, with many unresolved questions [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur report presents the procedure that led to the diagnosis of the congenital form of TTP in an adult patient - a pregnant woman. Importantly, thanks to the rapid establishment of the diagnosis and the implementation of optimal treatment- enzyme replacement therapy with rADAMTS13, it was possible to successfully carry the pregnancy to a successful outcome, give birth to a healthy child, and have an uncomplicated postpartum course.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eADAMTS13 -\u0026nbsp;a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13\u003c/p\u003e\n\u003cp\u003eAPS - antiphospholipid syndrome\u003c/p\u003e\n\u003cp\u003ecTTP - congenital TTP\u003c/p\u003e\n\u003cp\u003eDAT - direct antiglobulin test\u003c/p\u003e\n\u003cp\u003eFFP - fresh frozen plasma\u003c/p\u003e\n\u003cp\u003eiTTP - immune-mediated TTP\u003c/p\u003e\n\u003cp\u003eLMWH - low molecular weight heparin\u003c/p\u003e\n\u003cp\u003ePNH - paroxysmal nocturnal hemoglobinuria\u003c/p\u003e\n\u003cp\u003erADAMTS13 - recombinant ADAMTS13\u003c/p\u003e\n\u003cp\u003eSPC - summary of product characteristics\u003c/p\u003e\n\u003cp\u003eTMA - thrombotic microangiopathy\u003c/p\u003e\n\u003cp\u003eTTP - thrombotic thrombocytopenic purpura\u003c/p\u003e\n\u003cp\u003eUL-VWF - ultra-large von Willebrand factor multimers\u003c/p\u003e\n\u003cp\u003euTTP - unidentified pathophysiology\u003c/p\u003e\n\u003cp\u003evWF - von Willebrand factor\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003eAll procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Authors obtained patient\u0026rsquo;s informed consent for publication.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis work was supported by Uniwersytet Rzeszowski.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eBBO: substantial contributions to the conception, acquisition, analysis and interpretation of data and drafting the work; KKO: substantial contributions to the acquisition, analysis and interpretation of data and drafting the work; AK: substantial contributions to acquisition, analysis and interpretation of data; SK: substantial contributions to the acquisition of data; AWP: substantial contributions to the acquisition of data; DO: substantial contributions to the acquisition of data; JZ: substantial contributions to analysis and interpretation of data; TI: substantial contributions to analysis and interpretation of data; TK: substantial contributions to the acquisition, analysis and interpretation of data; MM: drafting the work and reviewing it critically for important intellectual content, final approval for all aspects of the version of the work to be published in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJoly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129(21):2836\u0026ndash;46. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood-2016-10-709857\u003c/span\u003e\u003cspan address=\"10.1182/blood-2016-10-709857\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKremer Hovinga JA, George JN. Hereditary Thrombotic Thrombocytopenic Purpura. 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Blood. 2014;124(2):211\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/blood-2014-02-553131\u003c/span\u003e\u003cspan address=\"10.1182/blood-2014-02-553131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026eacute;ranger N, Coppo P, Tsatsaris V, Boisseau P, Prov\u0026ocirc;t F, Delmas Y, Poullin P, Vanhoorelbeke K, Veyradier A, Joly BS. Management and follow-up of pregnancy-onset thrombotic thrombocytopenic purpura: the French experience. Blood Adv. 2024;8(1):183\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/bloodadvances.2023011972\u003c/span\u003e\u003cspan address=\"10.1182/bloodadvances.2023011972\" 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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"congenital thrombotic thrombocytopenic purpura, pregnancy, recombinant ADAMTS13","lastPublishedDoi":"10.21203/rs.3.rs-9483019/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9483019/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough cTTP results from a congenital mutation of the ADAMTS13 gene, in some cases the manifestation of the disease depends on an additional triggering factor, and the diagnosis is made in adulthood.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe present the case of a 30-year-old woman with a history of ischemic strokes and one miscarriage, in whom at the 24th week of her second pregnancy, cTTP was diagnosed as a result of extensive hemolytic anemia diagnostics. After a complicated initial treatment using FFP, replacement therapy with recombinant ADAMTS13 was applied. On the 37th day of treatment, due to the diagnosis of preeclampsia, the pregnancy was terminated by cesarean section without complications.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDespite the diagnosis of a life-threatening disease for both the mother and fetus, the applied management allowed the pregnancy to be successfully brought to term, resulting in the birth of a healthy child and an uncomplicated postpartum course.\u003c/p\u003e","manuscriptTitle":"Successful course of pregnancy and childbirth despite the diagnosis of congenital thrombotic thrombocytopenic purpura in the pregnant woman","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 06:22:30","doi":"10.21203/rs.3.rs-9483019/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"36180739940608527134600585190456835326","date":"2026-04-29T20:17:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-29T10:10:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-23T13:13:31+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-23T13:13:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"Thrombosis Journal","date":"2026-04-21T10:36:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd82456a-0780-47f6-abf5-03d702e7feb1","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"36180739940608527134600585190456835326","date":"2026-04-29T20:17:24+00:00","index":11,"fulltext":""},{"type":"reviewersInvited","content":"4","date":"2026-04-29T10:10:04+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T06:22:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 06:22:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9483019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9483019","identity":"rs-9483019","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}