Maternal and fetal outcomes in immune-mediated thrombotic thrombocytopenic purpura: A scoping review Free

Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy due to a severely deficient ADAMTS13 activity caused by ADAMTS13 autoantibodies. Pregnancy is a recognized risk for precipitating acute episodes of iTTP. iTTP is immediately life-threatening to both mother and fetus. This scoping review explores the neonatal outcomes of pregnant mothers with iTTP.

Methods: We performed a comprehensive literature search (1990 to 2023) in major scientific databases using the Ovid MEDLINE, Embase, EBM Reviews (Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), and Scopus to identify studies related to iTTP and pregnancy outcomes. Eligible studies included those published in English that reported women with a diagnosis of iTTP that later become pregnant, or women that were initially diagnosed with iTTP during pregnancy or postpartum. Cases were included if there was documentation of confirmed ADAMTS13 deficiency and ADAMTS13 inhibitor was positive or if the author indicated cases were acquired or iTTP. Results were displayed descriptively. Two authors reviewed titles and abstracts, and a third author resolved conflicts. Relevant studies were extracted and analyzed descriptively.

Results: 125 publications underwent full review; 52 publications (38 manuscripts, 13 abstracts) consisting of case series (n=18) and case reports (n=33) were included in final analysis. 1 review article with a case series was also included.

Data regarding 206 pregnancies (antepartum iTTP: n=91, postpartum iTTP: n=24, and pregnancies in patients with a history (hx) of iTTP but no iTTP during current pregnancy: n=91) from 158 patients was included. Antepartum iTTP presented in the first, second and third trimesters in 21%, 38.7%, and 40 % respectively. When reported (n=67), plasma exchange (TPE) was used in 92.5% cases of iTTP. In 3 pregnancies, FFP was used instead of TPE, Rituximab was used in 19 (7 antepartum) and caplacizumab was used in 6 (2 antepartum) cases of ITTP.

Of pregnancies with antepartum iTTP or with a hx of iTTP (n=182), fetal outcomes were available in 161 pregnancies. Of these, there were 46 fetal deaths (28.6%) and 31/46 (67.4%) occurred in those with antepartum iTTP. Fetal outcomes were available in 84/91 pregnancies with a hx of iTTP with no acute iTTP at current pregnancy and 82% (69/84) resulted in a live birth.

ADAMTS13 activity was available in 58/91 pregnancies with a hx of iTTP with no acute iTTP and 88 % of these pregnancies had ADAMTS13> 20%. Of pregnancies with a hx of iTTP and available ADAMTS13, there were 7 fetal deaths; one was unrelated to iTTP. The remainder occurred in the first trimester (n=4) and second trimester (n=2); ADAMTS13 was < 20% in 3 patients, and > 20% in 3 patients. Of those with pregnancy losses with ADAMTS13> 20%, one patient had two other miscarriages (one before diagnosis of iTTP and one after diagnosis but no ADAMTS13 available). Another had a pregnancy with a live birth 2 years later (no ADAMTS13 available) and the third patient had ADAMTS13> 20% with a positive inhibitor. In pregnancies with both fetal outcomes and ADAMTS13 activity (n=53), live-births trended towards higher ADAMTS13 activities compared to fetal demise (p, 0.066).

There were 5 maternal deaths associated with pregnancy (antepartum iTTP:4, postpartum iTTP: 1). Of those not receiving TPE (n=5), one pregnancy was associated with maternal and fetal death due to late iTTP recognition, one patient was lost to follow-up post-delivery to a live infant. The other three patients received FFP, and steroids; one of these patients suffered a fetal loss.

Fetal outcomes were available in 5/7 pregnancies using antepartum rituximab and 4/5 were associated with fetal demise. In pregnancies using antepartum caplacizumab, there was one fetal death and one live birth.

Conclusions: Pregnancy in patients with a diagnosis of iTTP carries significant associated morbidity and mortality. To our knowledge, this is the most comprehensive report on fetal mortality. With 28.6% of fetal demise, it is significantly higher than the fetal mortality in the general population (5.5 fetal deaths per 1000 live births). In the current cohort, 82% of pregnancies occurring in women with a hx of iTTP but without acute iTTP resulted in a live birth. This supports benefit of optimizing ADAMTS13 activity in women with a hx of iTTP interested in pregnancy.