Abstract
BACKGROUND: Patients suffering from hemolytic anemia, thrombocytopenia, and organ damage may suffer from microangiopathic anemia, also called thrombotic microangiopathy (TMA). This condition is caused by many different pathogenic mechanisms and is always life-threatening due to vessel occlusion in vital organs. Rapid and careful workup is mandatory to identify the cause of TMA. To identify patients suffering from immune-mediated thrombotic thrombocytopenic purpura (iTTP), ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) measurement is mandatory. All patients with ADAMTS13 activity below 10 IU/dL are assigned to the diagnosis iTTP and need urgent targeted treatment. Meanwhile, caplacizumab - an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment - is approved for the treatment of iTTP. Patients with TMA and ADAMTS13 activity>10 IU/dL can be assigned to other forms of TMA such as hemolytic uremic syndrome (HUS), complement-mediated TMA (cmTMA) - previously assigned to the term atypical HUS (aHUS) - or TMA secondary to underlying diseases such as autoimmune disorders, cancer, or infectious diseases. Complement inhibition with C5 targeted treatment, such as eculizumab or ravulizumab, is approved for the treatment of cmTMA. Even more challenging may be the differential diagnosis in pregnancy, in cancer patients with complex medication and the need to rule out conditions imitating TMA such as Evans syndrome, intoxication, infection, or severe vitamin B12 deficiency. SUMMARY: Identifying TMA and defining the pathophysiology of TMA is urgently necessary in patients with thrombocytopenia and hemolytic anemia with or without obvious organ damage. KEY MESSAGE: ADAMTS13 testing is the most important specific test to classify TMA.