The utility of platelet activation biomarkers in thrombotic microangiopathies

Primary thrombotic microangiopathies (TMAs) are observed in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), while secondary TMAs have a wide range of etiologies. Early diagnosis and treatment of TMA are critical for patient well-being; however, distinguishing TTP from HUS on presentation is particularly challenging. Thrombocytopenia and platelet activation are central to different types of TMAs, thus limiting the utility of standard diagnostic approaches to evaluate the platelet function and hemostatic capacity. Alternative means of quantifying and monitoring changes to platelet activation and function are urgently needed. Activated platelets have been shown to interact with proteins of the complement and coagulation cascades and form part of inflammation processes engaged in TMA. Increased levels of platelet surface receptors as well as increased plasma levels of platelet-derived soluble proteins have been reported in TMAs. Elevated levels of platelet-leukocyte aggregates and platelet microparticles are also reported in different types of TMAs. Larger prospective evaluations of platelet activation markers in TMA using standardized assays, with comparison to cohorts of patients with thrombosis, coagulopathy, and thrombocytopenia, to evaluate the clinical usefulness of platelet markers in TMA are now needed. This review will summarize the current knowledge around platelet activation markers and critically evaluate their utility in diagnosis and prognosis of TMA patients.