The Differential Diagnosis and Treatment of Thrombotic Microangiopathies

Background: Thrombotic microangiopathies are rare, life-threatening diseases whose care involves physicians from multiple specialties. The past five years have seen major advances in our understanding of the pathophysiology, classification, and treatment of these conditions. Their timely diagnosis and prompt treatment can save lives. Methods: This review is based on pertinent articles published up to 17 December 2017 that were retrieved by a selective search of the National Library of Medicine's PubMed database employing the terms "thrombotic microangiopathy," "thrombotic thrombocytopenic purpura," "hemolytic-uremic syndrome," "drug-induced TMA," and "EHEC-HUS." Results: The classic types of thrombotic microangiopathy are thrombotic thrombo cytopenic purpura (TTP) and typical hemolytic-uremic syndrome (HUS), also known as enterohemorrhagic Escherichia coli-associated HUS (EHEC-HUS). There are a number of further types from which these must be differentiated. The key test, beyond a basic hematological evaluation including a peripheral blood smear, is measurement of the blood level of the protease that splits von Willebrand factor, which is designated ADAMTS13 (a disintegrin and metalloprotease with thrombo spondin type 1 motif, member 13). The quantitative determination of ADAMTS13, of ADAMTS13 activity, and of the ADAMTS13 inhibitor serves to differentiate TTP from other types of thrombotic microangiopathy. As TTP requires urgent treatment, plasmapheresis should be begun as soon as TTP is suspected on the basis of a finding of hemolysis with schistocytes and thrombocytopenia. The treatment should be altered as indicated once the laboratory findings become available. Conclusion: Rapid differential diagnosis is needed in order to determine the specific type of thrombotic microangiopathy that is present, because only patients with TTP and only a very small percentage of those with atypical hemolytic-uremic syndrome (aHUS) can benefit from plasmapheresis. The establishment of a nationwide registry in Germany with an attached biobank might help reveal yet unknown genetic predispositions.