ADAMTS, Thrombotic Thrombocytopenic Purpura and Pregnancy

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) which pathophysiology mainly relies on a severe deficiency (either acquired or inherited) of ADAMTS13, the specific von Willebrand factor (VWF) protease. TTP is characterized by a feminine predominance and pregnancy is a precipitating factor for TTP boots. Obstetrical TTP represents at least 20% of all TTP occurring in child-bearing age women.In this review, an analyze of the English-language literature from 1955 to 2011 found about 350 cases of obstetrical TTP including about 40 case-reports/-series with well documented ADAMTS13 investigation (32 inherited and 17 acquired TTP with severe ADAMTS13 deficiency). In the 32 patients with inherited TTP, the first pregnancy was systematically associated with a TTP boot, mostly occurring during the third trimester; curative plasma therapy (PT) allowed a good maternal outcome although the fetal outcome was almost systematically bad. In the 17 patients with acquired TTP, TTP also occurred mostly de novo during the first pregnancy and after 20 weeks gestation; curative PT usually allowed a good maternal outcome and the birth of an alive baby in about 2 cases/3.The diagnosis of obstetrical TTP is challenging because it mostly occurs in women with no antecedent of TTP and it has no specific clinical/biological symptoms except a severely deficient ADAMTS13. However, because of the severity of the prognosis in the absence of urgent treatment, any thrombocytopenia +/-hemolytic anemia in a pregnant woman with no alternative diagnosis to TMA should be considered as TTP.The management of an obstetrical TTP boot consists in a blood collection for ADAMTS13 investigation followed by an emergency first-line treatment with PT yielding a maternal response rate of about 80% although the global stillbirth rate is likely to be close to 50%.The follow-up of women who recovered from an obstetrical TTP boot should include a complete ADAMTS13 investigation to distinguish between the inherited and the acquired form of TTP, in order to both estimate the risk for relapse and optimize prophylaxis indication during subsequent pregnancies. The relapse rate appears to be 100% in inherited TTP and about 20% in acquired TTP. Early prophylactic PT is thus indicated systematically in inherited TTP as it is clearly beneficial for both the mother and the fetus outcomes. In contrast, the optimal management is still debated in subsequent pregnancies of women with acquired TTP whose clinical and biological monitoring should be very careful.TTP is a very rare complication of pregnancy (about 1/100,000 pregnancies) but it is a life-threatening disease for both the mother and the fetus. Many advances have been performed in the last 10 years in terms of diagnosis and treatment. However, clear guidelines are still needed to optimize the management of subsequent pregnancies, which may be significantly different as a function of the pathophysiology for ADAMTS13 deficiency.

Incidence of obstetrical thrombotic thrombocytopenic purpura in a retrospective study within thrombocytopenic pregnant women. A difficult diagnosis and a treatable disease

“…Similar patients with spontaneous resolution of pregnancy-triggered TTP have been described by Fujimura et al in Upshaw-Schulman families [15], and others since then have been reviewed in Veyradier et al [5]. However, fatal TTP in the setting of pregnancy is commonly reported, and prompt plasma exchange is mandatory [23].…”

How I treat thrombocytopenia in pregnancy

“…73 The risk of relapse during a subsequent pregnancy in women with acquired TTP associated with severe ADAMTS13 deficiency has been reported to be ϳ 20%. 74 Our practice is to monitor women closely throughout their pregnancy and start prophylactic plasma exchange treatment if ADAMTS13 activity falls below Ͻ 10% or the blood film shows unequivocal evidence of red cell fragmentation.…”

Pregnancy in Upshaw-Schulman syndrome

“…Pregnancy constitutes a trigger for severe acute TTP episodes in patients with USS (12,32). Pregnancy or the post-partum period is an associated or underlying condition in 10-30% of adult-onset TTP (7,15,26,31), with an unexpected high frequency of USS cases among such cases (10/42; 24%) in a recent publication of the French TMA registry (21).…”

“…The majority of patients become symptomatic in the late second to early third trimester of pregnancy. An earlier manifestation was associated with worse pregnancy outcome (7,32).…”