Hereditary thrombotic thrombocytopenic purpura (hTTP) results from bi-allelic ADAMTS13 mutations and severe congenital ADAMTS13 deficiency. Affected patients are particularly vulnerable during infancy and pregnancy, where acute episodes are often severe, presenting with thrombocytopenia, haemolytic anemia and symptoms of organ ischemia. Today, many patients receive regular plasma infusions to prevent morbidity (i.e. strokes) and mortality. We aimed to characterize the impact of hTTP diagnosis and the effect of plasma prophylaxis on pregnancy outcomes.

Observational study on female patients with confirmed hTTP diagnosis (ADAMTS13 activity <10%, bi-allelic ADAMTS13 mutations) enrolled in the International hTTP Registry (NCT01257269) before June 30, 2023. Documented pregnancies were divided into before (retrospective, incl. index pregnancy) and after (prospective) hTTP diagnosis.

Of the 131 female hTTP patients enrolled, 87 (66.4%) had been pregnant one or several times, resulting in 214 documented pregnancies. Half of these patients (n=44, 50.6%) received their hTTP diagnosis because of obstetrical complications (index pregnancy) at a median maternal age of 26.7 (IQR, 23.5-31.2). The live-birth rate for the 125 retro- and 89 prospectively followed pregnancies was 52.8% (n=66) and 79.8% (n=71), respectively. Miscarriage was the main adverse outcome in retro- and prospectively followed pregnancies (n=30, 50.8%; vs. n=13, 72.2%), followed by late abortion (n=14, 23.7%; n=4, 22.2%). Stillbirth (n=7, 11.9%) and neonatal death (n=8, 13.6%) were observed only before hTTP diagnosis. Continued plasma prophylaxis, or prophylactic plasma infusions started in on-demand treated patients when pregnancy was recognized, increased live-birth rates to 85.7% and 76.2%, respectively, compared to 37.5% in patients without treatment. In 10/88 (11.4%) pregnancies after hTTP diagnosis, aspirin was given in addition (live-birth rate 80%). Acute TTP episodes and occurrence of preeclampsia were lowest in patients on plasma prophylaxis before becoming pregnant.

A diagnosis of hTTP leading to plasma prophylaxis during pregnancy reduces maternal morbidity and increases the live-birth rate considerably. The earlier plasma prophylaxis is started, the larger the positive effect. As hTTP confers an increased risk for preeclampsia, the low prescription rate of aspirin leaves room for improvement.