Recognizing anemia and thrombpenia in acute and emergency medicine is easy. Acute (microangiopathic hemolytic) anemia and thrombopenia can be a sign of thrombotic microangiopathy (TMA). TMA syndromes are potentially life-threatening diseases. Diagnosing a TMA syndrome, causal differentiation and treatment require specialist knowledge that is not always available in acute and emergency medicine. Many differential diagnoses and examinations are usually necessary to make a correct diagnosis. Therefore, a standardized diagnostic algorithm is helpful for early diagnosis and treatment initiation.