Patient Experience with Congenital (Hereditary) Thrombotic Thrombocytopenic Purpura: A Conceptual Framework of Symptoms and Impacts.

Defective processing of unusually large von Willebrand factor multimers and thrombotic thrombocytopenic purpura

Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias.

Is Upshaw–Schulman syndrome congenital thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome? Yes to both

Thrombotic microangiopathies (TMAs) include several diseases, most prominently thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) characterized by profound thrombocytopenia and microangiopathic hemolytic anemia. Usually congenital TTP is due to mutations in the gene ADAMTS13 or idiopathic when autoantibodies against ADAMTS13 are defined. The differential diagnosis of TTP from other TMAs can be sometimes challenging even with the discovery of ADAMTS13 for more than a decade. The presence of ADAMTS13 activity does not rule out TTP and ultra-large von Willebrand factor (ULVWF) multimers not always present in plasma of patients with TTP. Pathogenesis of TTP is related to massive intravascular aggregation of platelets as a result of lack of degradation of ULVWF multimers because of a lack of ADAMTS13 or secretion of excessive ultra-large multimers by endothelial cells. Diagnostic criteria of TTP are based on clinical features of neurological and renal disfunction along with hemolytic anemia, severe thrombocytopenia, low ADAMTS13 activity, and mutation in ADAMTS13 gene when congenital TTP is suspected. The standard treatment of TTP includes plasma exchange or plasma infusion. Splenectomy, protein A immunoadsorbtion, immunosuppressive drugs, and CD20 antibodies against B cells like rituximab are also used. Recombinant ADAMTS13 in congenital TTP is still to be used only in clinical trials. In HUS plasmapheresis is not efficient. Treatment of other TMA diseases is based on their underlying conditions.

Thrombotic Thrombocytopenic Purpura and Atypical Hemolytic Uremic Syndrome in Pregnancy: A Single Center Retrospective Review

ADAMTS13: what it does, how it works, and why it's important

Proteolytic cleavage of von Willebrand factor by ADAMTS‐13 prevents uninvited clumping of blood platelets

Single-Center Experience of the Utility of a Rapid ADAMTS13 Assay

Genotyp-Phenotype Correlation in Congenital ADAMTS13 Deficient Patients

Siblings with congenital thrombotic thrombocytopenic purpura.

Pathogenesis and novel treatment of thrombotic thrombocytopenic purpura

Natural History of Patients Affected with Thrombotic Thrombocytopenic Purpura: Milan TTP Registry

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening thrombotic microangiopathy (TMA) caused by severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13. Pregnancy is a recognized trigger for both immune-mediated and congenital TTP and is associated with increased maternal and fetal morbidity. Clinical overlap with other pregnancy-associated TMAs, including preeclampsia and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, often delays diagnosis. This review synthesizes current evidence on pathophysiology, diagnostic uncertainty, and gestation-specific management of pregnancy-associated TTP, highlighting differences between immune-mediated and congenital disease. Methods: This is a narrative review. We performed a targeted literature search of PubMed/MEDLINE (from inception to December 2025) to identify English-language publications. The study types included were case reports/series, observational studies, large database studies, randomized trials, reviews, and relevant guidelines addressing TMA in pregnancy, with emphasis on immune-mediated and congenital TTP. Search terms included "pregnancy", "thrombotic thrombocytopenic purpura", "hereditary TTP", "acquired TTP", "ADAMTS13," "thrombotic microangiopathy," "HELLP," "postpartum", and "complement-mediated TMA" alone or in combination. The search was supplemented by manual screening of reference lists and key guidelines. Articles were selected based on relevance to diagnosis and management of pregnancy-associated TTP. Conference abstracts and non-peer-reviewed sources were not routinely included and were considered only when peer-reviewed evidence was limited. Results: Pregnancy-associated TTP remains a major diagnostic challenge due to overlapping clinical and laboratory features with other obstetric thrombotic microangiopathies. Distinguishing immune-mediated from congenital TTP is essential, as management and prognosis differ substantially. Prompt recognition and early initiation of therapeutic plasma exchange, immunosuppression, or prophylactic plasma therapy markedly improve maternal outcomes. Rapid ADAMTS13 testing, structured risk stratification, and multidisciplinary care are central to optimal management. Fetal outcomes are closely linked to gestational age at onset and timeliness of therapy. Conclusions: Early differentiation of TTP from other pregnancy-associated TMAs is critical for maternal and fetal survival. Advances in rapid ADAMTS13 diagnostics and emerging targeted therapies, including caplacizumab and recombinant ADAMTS13, offer opportunities to improve precision management and outcomes in future pregnancies.

The frontline of TMA management

Thrombotic thrombocytopenic purpura (TTP) is an acute life threatening disorder associated with a deficiency in the enzyme ADAMTS 13. It is diagnosed by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and widespread microvascular thrombosis resulting in organ ischaemia. Approximately 70% of TTP cases occur in women and nearly half of these women are of childbearing age. Pregnancy is a recognised precipitating cause of TTP in between 10‐25% of all cases and includes patients with acquired antibody mediated TTP and congenital TTP, often presenting in adult hood. The availability of ADAMTS 13 assays allows differentiation between congenital and acquired TTP and appropriate treatment plans. There is also a subsequent risk of TTP relapse in women with previous non‐pregnancy related TTP. Presentation may occur at any stage in pregnancy or in the post partum period. This would suggest an hormonal influence as well as the reduction in ADAMTS 13 from the second trimester, related to pregnancy associated increase in Von Willebrand Factor. Differentiation from other pregnancy associated microangiopathies, such as pre‐eclampsia, HELLP (haemolysis, elevated liver enzymes and low platelets) or HUS (haemolytic Uraemic Syndrome) may be clinically difficult, but necessary, in part, because of differences in treatment. HELLP and pre‐eclampsia require delivery and HUS supportive care. TTP requires urgent treatment with plasma exchange (PEX) to attain remission, but also to prevent fetal abnormalities resulting from placental thrombosis. Presented is a review of the literature of pregnancy associated TTP and our experience of treatment of patients who present with TTP during pregnancy and monitoring of women who have had a history of TTP. Positive outcome in pregnancy has been associated with regular monitoring of routine laboratory parameters and ADAMTS 13 activity. All patients maintain low dose aspirin therapy and low molecular weight heparin is started in those women where an increased thrombotic risk is determined. The aim is to optimise implantation and preservation of placental function, especially in women with previous pregnancy loss, as abnormalities of the uteroplacental circulation resulting in insufficiency are established early in the first trimester. A significant reduction in ADAMTS 13 activity or reduction in platelet count below the normal range, PEX is undertaken to prevent any further deterioration. Frank relapse is treated with daily PEX. In women with a congenital TTP phenotype, regular treatment through pregnancy has been successfully undertaken. It is very difficult to devise evidence based guidelines for pregnancy in women with a history of TTP. In our cohort, patients with ADAMTS 13 activity < 5% at presentation in the current pregnancy had a history of TTP precipitated during pregnancy or recurrent TTP episodes, such that the chance of further exacerbation during pregnancy was considered to be high. Indeed, cases 1, 2 and 4 have demonstrated ADAMTS 13 activity < 5% before and after these pregnancies and only case 3 and 5 had further TTP episodes following pregnancy. Therefore the intensive monitoring and treatment was based on the high probability of relapse during pregnancy. Indeed, in Patients with normal ADAMTS 13 activity at the start of pregnancy were continually monitored, but did not have a TTP relapse. In Conclusion: a multidisciplinary approach to pregnancy care with regular monitoring of routine laboratory parameters and ADAMTS 13 activity during pregnancy allows pre‐emptive treatment of patients who are at risk from TTP relapse.