Complications of Pregnancy in Women with Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura (TTP) occurring in association with pregnancy or puerperium accounts for 12–25% of all TTP acute episodes. Pregnancy leads to acute TTP in women affected by congenital TTP in the absence of periodic prophylactic plasma infusions, while the risk of acute TTP during pregnancy for women with the acquired form is not well known. Moreover, it is not known whether the presence of anti-ADAMTS13 antibodies that characterize acquired TTP affect the outcome of subsequent pregnancies. The aim of this study was to evaluate maternal-foetal outcome of pregnancies started after the diagnosis of TTP.

We analyzed clinical and laboratory features of 25 pregnancies of 22 women with TTP (all acquired TTP) out of 320 TTP patients in our cohort, all referred to the Milan TTP Registry, Milan (Italy), from 1994 to 2012. We tested the available biological samples for ADAMTS13 activity using FRET method, anti-ADAMTS13 autoantibodies by Western Blotting and ultra-large von Willebrand Factor (ULVWF) multimers ratio.

We found that 18 out of 25 pregnancies (72%) were complicated by either TTP recurrence (11/25, 44%) or spontaneous abortion in the first trimester (7/25, 28%). The incidence of TTP recurrence was 0.02 cases/week gestation (median duration of pregnancy at event: 32 weeks). The incidence of spontaneous abortion was 0.01 cases/week gestation (median duration of pregnancy at event: 6 weeks). Women's parity was associated with spontaneous abortion, with a relative rate of 2.8 (95% confidence interval: 0.5–14.2) for multigravidae versus primigravidae.

Interestingly, almost all miscarriages (6/7, 86%) occurred in women who experienced a pregnancy-related TTP episode during a previous pregnancy. To understand if this high rate of spontaneous abortion could be related to TTP, we analyzed ADAMTS13 activity levels, anti-ADAMTS13 antibodies and ULVWF multimers pattern. In the pregnancies complicated by TTP relapse, ADAMTS13 activity was severely reduced in the acute phase, in association with the presence of antiADAMTS13 antibodies and reduction of ULVWF multimers (ULVWF ratio < 0.85); in the cases of pregnancies complicated by spontaneous abortion, the mean ADAMTS13 activity level in the first trimester was 31%, with the presence of antiADAMTS13 antibodies and excess of ULVWF multimers (ULVWF ratio > 1.21); in the group of uncomplicated pregnancies, the mean ADAMTS13 activity levels was 97% in the first trimester and remained > 35% until delivery, with absence of antiADAMTS13 antibodies and normal ULVWF multimers.

Obstetric complications are frequent during pregnancies in women affected with acquired TTP. ADAMTS13 activity levels > 35% in the absence of antiADAMTS13 antibodies seem to confer little or no risk, while lower ADAMTS13 activity levels and the presence of antiADAMTS13 antibodies during pregnancy are predictive of poor gravidic outcome, either with acute TTP or spontaneous abortion in the first trimester. Surprisingly, although confidence intervals were wide, miscarriage rates were highest in multigravidae. Pre-gravidic and gravidic monitoring of ADAMTS13 activity levels and anti-ADAMTS13 autoantibodies is crucial in the management of pregnancies in TTP patients.

No relevant conflicts of interest to declare.