ADAMTS13 activity and the risk of thrombotic thrombocytopenic purpura relapse in pregnancy

Thrombotic thrombocytopenic purpura (TTP) associated with pregnancy accounts for 12–31% (George, 2000; Ridolfi & Bell, 1981; Wurzei, 1979) of TTP cases and is associated with high rates of obstetric complications (Scully et al, 2006; Vesely et al, 2004; Wurzei, 1979). Given that reported rates of recurrent TTP in future pregnancies varies widely (12–61%) (Vesely et al, 2004) and prophylactic plasma exchange (PE) may be associated with complications, identifying pregnant patients at the greatest risk for relapse would be of considerable interest. We report five pregnancies in three patients with a history of TTP (identified from a cohort of TTP patients enrolled in prospective studies at the Ohio State University and followed longitudinally over a median of 48 months) in the context of serial measurement of ADAMTS13 activity. Enrollment criteria for all studies included a microangiopathic haemolytic anaemia and thrombocytopenia (<100 · 10/l) without an alternative explanation. ADAMTS13 biomarker studies were obtained every 3 months using a methodology reported previously (Jin et al, 2006) (Tables I and II). Patient 1, a 22-year-old female, presented acutely ill at 22 weeks of gestation with intrauterine fetal death, thrombocytopenia (3 · 10/l), elevated lactate dehydrogenase (LDH; 2545 u/l, normal 0–190 u/l) and microangiopathic haemolytic anaemia. She was enrolled on a therapeutic study of PE and corticosteroids, but eventually required cyclosporine (CSA) at a dose of 100 mg BID to be successfully weaned from PE. Within 4 weeks of stopping her planned 6-month course of CSA she became pregnant and presented with a platelet count of 21 · 10/l and LDH of 1428 u/l in her 22nd week of gestation. PE was initiated but secondary to her deteriorating clinical status, labour was induced and the baby died soon after birth. Following remission she was discharged on CSA but lost to follow up. After 11 months she re-presented 17 weeks pregnant on CSA and chose to continue it despite the risks. In her 24th week she developed pre-eclampsia (without any signs of TTP) requiring a cesarean section, delivering a premature but healthy baby. She continued CSA until 4 weeks postpartum. ADAMTS13 activity dropped to <2Æ5% following discontinuation of CSA, but she has remained in clinical remission for 4 years since this last episode. Patient 2, a 22-year-old Caucasian female, presented with a platelet count of 6 · 10/l, LDH of 1156 u/l and microangiopathic features. She was enrolled in a therapeutic study and was randomized to concurrent CSA and PE. After being successfully tapered from PE she continued CSA for what was a planned 6-month course of therapy. However, after four additional weeks of therapy she became pregnant and CSA was discontinued. As noted in Table II, her ADAMTS13 activity