Differentiating and Managing Rare Thrombotic Microangiopathies During Pregnancy and Postpartum

Abstract

The most common thrombotic microangiopathy (TMA) of pregnancy is the well-recognized syndrome of preeclampsia with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. However, rare TMAs, including thrombotic thrombocytopenic purpura, complement-mediated hemolytic-uremic syndrome, and catastrophic antiphospholipid syndrome, may occur during pregnancy or postpartum and present with features similar to those of preeclampsia with severe features. Early recognition and treatment of these infrequently encountered conditions are key for avoiding serious maternal morbidities with long-term sequelae and possible maternal or fetal death. Differentiating between preeclampsia with severe features and these rare TMAs is diagnostically challenging as there is significant overlap in their clinical and laboratory presentation. Given the rarity of these TMAs, high-quality evidencebased recommendations on diagnosis and management during pregnancy are lacking. Using current objective information and recommendations from working groups, this report provides practical clinical approaches to diagnose and manage these rare TMAs. This report also discusses how to manage individuals with a history of these rare TMAs who are planning to conceive. To optimize favorable outcomes, a multidisciplinary approach including obstetricians, maternalfetal medicine specialists, hematologists, and nephrologists alongside close clinical and laboratory monitoring is vital.

Pregnancy as a susceptible state for thrombotic microangiopathies

“…The detection of MAHA in a pregnant or newly delivered patient constitutes a diagnostic and therapeutic emergency. In this context, algorithms for the management of pregnancy-related TMA are regularly updated, considering the challenge of urgent differentiation ( 5 , 21 , 34 ). Table 1 provides a concise overview of pregnancy-specific and -associated TMAs, focusing on the distinguishing features of different forms of TMA.…”

“…The recommended initial workup for pregnant or postpartum women presenting with TMA is detailed in recent reviews ( 5 , 21 ). This workup includes coagulation tests, quantification of ADAMTS-13 activity, investigation of autoimmune disorders (lupus anticoagulant, anticardiolipin antibodies, Beta-2-glycoprotein antibodies, antinuclear antibody) or metabolite deficiencies (vitamin B9, B12), exploration of complement levels (C3, C4, factor H, factor H autoantibody, factor I, factor B, and MCP/CD46 expression by flow cytometry), and, when available, measurement of sFLT1 and PlGF concentrations.…”

“…This review will examine the characteristics of TMA during pregnancy, refraining from detailed one-by-one descriptions and excluding discussions on management, as these have recently been comprehensively addressed ( 4 , 5 , 21 ). Instead, we will emphasize available tools for distinguishing pregnancy-related TMAs, with special attention to the potential contributions of histopathological analysis.…”

HELLP Syndrome and Differential Diagnosis with Other Thrombotic Microangiopathies in Pregnancy

“…The borders between the different forms and presentations of TMAs are not well defined, so differential diagnosis may be difficult or even impossible because these conditions may coexist. To further complicate the diagnostic process, during pregnancy, the hematologic, proteinuria, and complement parameters have different reference than in nonpregnant patients [64]. The differential diagnosis between these diseases requires a careful clinical evaluation and, especially, an assessment of laboratory parameters.…”

“…A reduction in the platelet count is common in HELLP syndrome, TTP, and aHUS. However, profound thrombocytopenia should increase suspicion for TTP, particularly when the platelet count is <30,000/mm 3 [64]. In some cases with obstetric indications, it may be a priority to interrupt the pregnancy for the birth of the fetus.…”