Pregnancy complications in acquired thrombotic thrombocytopenic purpura: a case–control study

Abstract

BackgroundPregnant women with a history of acquired thrombotic thrombocytopenic purpura (TTP) are considered at risk for disease recurrence and might be at risk for miscarriage, similar to other autoimmune disorders. However, the exact entity of these risks and their causes are unknown. The aim of this study was to evaluate risk factors associated with adverse pregnancy outcome, in terms of both gravidic TTP and miscarriage, in women affected by previous acquired TTP.MethodsWe conducted a nested case–control study in women with a history of acquired TTP enrolled in the Milan TTP registry from 1994 to October 2012, with strict inclusion criteria to reduce referral and selection bias.ResultsFifteen out of 254 women with acquired TTP were included, namely four cases with gravidic TTP, five with miscarriage, and six controls with uncomplicated pregnancy. In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies. Reduced levels of ADAMTS13 activity (<25%) in the first trimester were associated with an over 2.9-fold increased risk for gravidic TTP and with an over 1.2-fold increased risk for miscarriage (lower boundary of the confidence interval of the odds ratio). In addition, the presence of anti-ADAMTS13 antibodies during pregnancy was associated with an over 6.6-fold increased risk for gravidic TTP and with an over 4.1-fold increased risk for miscarriage.ConclusionsADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP.

How I treat thrombotic thrombocytopenic purpura in pregnancy

“…The latter alarm threshold for ADAMTS13 activity has been chosen for 2 reasons: (1) the physiological decline of ADAMTS13 reaches a minimum activity of 25% to 30% during regular pregnancies in healthy women, 10 and (2) reduced levels of ADAMTS13 activity (,25%) in the first trimester may be associated with an increased risk of gravidic complications (both gravidic TTP and miscarriage). 22 Once the platelet count is .50 000/mL, low-dose aspirin and/or thromboprophylaxis with low-molecular-weight heparin can be considered to reduce the risk of additional placental vascular damage, based on fetal and placental scan and overall venous thrombotic risk. In our clinical practice, we do not routinely prescribe aspirin to all TTP women during pregnancy, unless there is a specific gynecologic indication, since the pathogenesis of clots in acute TTP does not depend on cyclooxygenasemediated platelet-platelet aggregation but on inappropriate ULVWF-mediated platelet clumping.…”

“…For the reasons above, in our clinical practice, we generally propose proper counseling with our female patients of childbearing age to discuss the option of gestation, preferably before they plan to conceive, and then we follow them together with our Obstetrics Unit for regular multidisciplinary controls. Women are informed that (1) the risk of TTP recurrence during pregnancy will never be zero but will be minimized through careful evaluation and a close ADAMTS13 monitoring during pregnancy, with maintenance of ADAMTS13 activity levels .20% to 25% 22 ; (2) in case of gravidic TTP recurrence, even despite proper treatment, the risk of fetal morbidity is not zero, especially for IUGR, miscarriage, and second-trimester stillbirth 6,22 ; and (3) there is an increased risk of other pregnancy complications (ie, PE), requiring close obstetrical follow-up.…”

ADAMTS13: origins, applications, and prospects

“…The increased susceptibility to consumptive thrombocytopenia in conjunction with changing levels of ADAMTS13 can result in complications that include maternal and fetal death. By monitoring ADAMTS13 activity and anti‐ADAMTS13 antibodies during pregnancy, the risk of developing a life‐threatening thrombocytopenic event can be assessed …”

Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura

“…In some institutions, women with a decreased ADAMTS13 activity (eg, <10 IU/dL) before or at the onset of pregnancy are offered an prophylactic rituximab therapy, with a goal to eliminate anti‐ADAMTS13 autoantibodies and normalize plasma ADAMTS13 activity before conception. Evidence of normal ADAMTS13 activity may be associated with a lower risk of relapse in women with a history of TTP 71,72 …”