First diagnosed inherited TTP combined with inherited thrombophilia in a pregnant woman

Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic disorder marked by microvascular platelet clumping, leading to low platelet count, hemolytic anemia, and various systemic complications. TTP can be either acquired (immune) or congenital (hereditary, also known as Upshaw-Schulman syndrome), the latter arising from mutations in the ADAMTS13 gene. Deficient ADAMTS13 activity results in abnormal von Willebrand factor (vWF) multimers, leading to platelet thrombus formation and TTP symptoms [1] [2].

Method

Case Report

A 26-year-old woman, previously diagnosed with a heterozygous factor II mutation (Prothrombin G20210A) and negative for antiphospholipid syndrome (APS), experienced severe preeclampsia during her first pregnancy in 2021 at seven months gestation. Prophylactic anticoagulation with low molecular weight heparin (LMWH) was initiated upon confirmation of her pregnancy, concerning the risk of thrombosis. We reviewed her anamnesis during her pregnancy, she exhibited no risk factors for thrombosis, maintained a normal BMI, and had no personal or family history of thrombosis or hematological disorders. At 32 weeks, she developed severe anemia, thrombocytopenia (28,000/µL), proteinuria, elevated D-dimers, hyperhomocysteinemia, and hypertension. Among other differential diagnoses (HELLP, HUS, AFLP, SLE ([Fig. 1])), TTP was suspected and ADAMTS13 activity was measured, revealing levels below 5%. Urgent delivery was conducted at 32 weeks of gestation, followed by plasma infusion and corticosteroids. Her baby didn’t have any complications and was healthy. Four months postpartum, her ADAMTS13 level was 4.7%, and dropped to 2.8% in September 2023 year, despite the inhibitor level being within the reference range. Presently, she feels well, apart from anxiety regarding her results and occasional fatigue. Physical examination, laboratory parameters, and vital signs show no abnormalities, and she is not on any medication.

Fig. 1 Differential diagnosis; We marked “+”- if the symptom or laboratory marker is common for diagnosis, and “-“ if it is uncommon. We marked both symbols if the presentation of pathology could have or could not have these parameters. NR – not reported

Results

Discussion

This case underscores the challenge of diagnosis and managing congenital TTP, especially during pregnancy. Elevated homocysteine levels and prothrombotic polymorphisms have been associated with TTP, indicating a complex interplay of factors [3]. Pregnancy can lead to exacerbation of TTP manifestations, with recurring complications observed, LMWH is not effective in preventing TTP exacerbation [4]. Limited data on pregnancy outcomes in congenital TTP patients necessitate further research [5] [6] [7].

Conclusion This case highlights the complexities of diagnosing and managing congenital TTP during pregnancy. Ongoing research, precise diagnostics, and tailored interventions are crucial. Continued monitoring and genetic analysis are essential, with samples sent to The Hereditary Thrombotic Thrombocytopenic Purpura Registry for further analysis. Documenting cases and advancing research remain pivotal for enhancing TTP management and patient outcomes.

 

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Conflict of Interest

There is no conflict of interests

• References

• 1 Kremer Hovinga JA, George JN.. Hereditary Thrombotic Thrombocytopenic Purpura. N Engl J Med 2019; 381 (17) 1653-1662
• 2 Joly BS, Coppo P, Veyradier A.. Thrombotic thrombocytopenic purpura. Blood. 2017; 129 (21) 2836-2846
• 3 Trisolini SM, Capria S, Cafolla A. et al. Inherited thrombophilia in patients with thrombotic thrombocytopenic purpura. Thromb Res 2009; 124 (04) 512-513
• 4 Kasht R, Borogovac A, George JN.. Frequency and severity of pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura. Am J Hematol 2020; 95 (11) E316-E318
• 5 Pérez-Rodríguez A, Lourés E, Rodríguez-Trillo Á. et al. Inherited ADAMTS13 deficiency (Upshaw-Schulman syndrome): a short review. Thromb Res 2014; 134 (06) 1171-1175
• 6 Battinelli EM.. TTP and pregnancy. Blood. 2014; 123 (11) 1624-1625
• 7 Knöbl P.. Inherited and acquired thrombotic thrombocytopenic purpura (TTP) in adults. Semin Thromb Hemost 2014; 40 (04) 493-502

Publication History

Article published online:
26 February 2024