Rare onset of congenital thrombotic thrombocytopenic purpura during pregnancy: A novel ADAMTS13 gene variant

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare autosomal recessive thrombotic microangiopathy caused by biallelic mutations in ADAMTS13, leading to severe enzyme deficiency. The absence of ADAMTS13 prevents cleavage of ultra-large von Willebrand factor multimers, resulting in platelet-rich microthrombi formation. Pregnancy is a known precipitation factor, and early diagnosis and plasma treatment regimen to increase the ADAMTS13 activity is essential to prevent maternal and fetal complications. We report the case of asymptomatic cTTP presenting in the third trimester of a first pregnancy. ADAMTS13 activity was <5%, and mixing studies excluded the presence of an inhibitor. Subsequent genetic testing revealed two pathogenic ADAMTS13 variants, including a previously unreported mutation, confirming the diagnosis of cTTP. The patient was treated with virus-inactivated fresh frozen plasma during pregnancy and later with prophylactic infusions during the postpartum period. No clinical relapses occurred during follow-up. This case highlights the diagnostic challenges of cTTP during pregnancy and emphasizes the importance of early ADAMTS13 activity testing, including inhibitor analysis. Although several international guidelines address cTTP management, individualized pregnancy and postpartum strategies remain essential. Our case supports the role of plasma prophylaxis and genetic confirmation in guiding long-term management plans for affected individuals.