Thrombotic thrombocytopenic purpura and pregnancy

Abstract

Thrombotic thrombocytopenic purpura (TTP) is an acute life threatening disorder associated with a deficiency in the enzyme ADAMTS 13. It is diagnosed by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and widespread microvascular thrombosis resulting in organ ischaemia. Approximately 70% of TTP cases occur in women and nearly half of these women are of childbearing age. Pregnancy is a recognised precipitating cause of TTP in between 10‐25% of all cases and includes patients with acquired antibody mediated TTP and congenital TTP, often presenting in adult hood. The availability of ADAMTS 13 assays allows differentiation between congenital and acquired TTP and appropriate treatment plans. There is also a subsequent risk of TTP relapse in women with previous non‐pregnancy related TTP. Presentation may occur at any stage in pregnancy or in the post partum period. This would suggest an hormonal influence as well as the reduction in ADAMTS 13 from the second trimester, related to pregnancy associated increase in Von Willebrand Factor. Differentiation from other pregnancy associated microangiopathies, such as pre‐eclampsia, HELLP (haemolysis, elevated liver enzymes and low platelets) or HUS (haemolytic Uraemic Syndrome) may be clinically difficult, but necessary, in part, because of differences in treatment. HELLP and pre‐eclampsia require delivery and HUS supportive care. TTP requires urgent treatment with plasma exchange (PEX) to attain remission, but also to prevent fetal abnormalities resulting from placental thrombosis. Presented is a review of the literature of pregnancy associated TTP and our experience of treatment of patients who present with TTP during pregnancy and monitoring of women who have had a history of TTP. Positive outcome in pregnancy has been associated with regular monitoring of routine laboratory parameters and ADAMTS 13 activity. All patients maintain low dose aspirin therapy and low molecular weight heparin is started in those women where an increased thrombotic risk is determined. The aim is to optimise implantation and preservation of placental function, especially in women with previous pregnancy loss, as abnormalities of the uteroplacental circulation resulting in insufficiency are established early in the first trimester. A significant reduction in ADAMTS 13 activity or reduction in platelet count below the normal range, PEX is undertaken to prevent any further deterioration. Frank relapse is treated with daily PEX. In women with a congenital TTP phenotype, regular treatment through pregnancy has been successfully undertaken. It is very difficult to devise evidence based guidelines for pregnancy in women with a history of TTP. In our cohort, patients with ADAMTS 13 activity < 5% at presentation in the current pregnancy had a history of TTP precipitated during pregnancy or recurrent TTP episodes, such that the chance of further exacerbation during pregnancy was considered to be high. Indeed, cases 1, 2 and 4 have demonstrated ADAMTS 13 activity < 5% before and after these pregnancies and only case 3 and 5 had further TTP episodes following pregnancy. Therefore the intensive monitoring and treatment was based on the high probability of relapse during pregnancy. Indeed, in Patients with normal ADAMTS 13 activity at the start of pregnancy were continually monitored, but did not have a TTP relapse. In Conclusion: a multidisciplinary approach to pregnancy care with regular monitoring of routine laboratory parameters and ADAMTS 13 activity during pregnancy allows pre‐emptive treatment of patients who are at risk from TTP relapse.