<unk>  is not the only condition that causes systemic TMA, a fact that makes differential diagnosis essential. Historically, the clinical diagnosis of TMA-causing diseases was grouped into a broad category that (in addition to<unk>  included thrombotic thrombocytopenic purpura (TTP) and Shiga-toxin-producing Escherichia coli<unk><unk>  syndrome (STEC-HUS). However, it is now understood that although<unk> , STEC-HUS, and TTP have similar clinical presentations, they have distinct causes and specific tests can be conducted to differentiate these diseases. In addition, there are other conditions that can cause TMA as a secondary manifestation; these entities include systemic lupus erythematosus (SLE), malignant hypertension, progressive systemic sclerosis (PSS, also known as scleroderma), the pregnancy-associated HELLP (hemolysis, liver dysfunction, and low platelets) syndrome, and toxic drug reaction (e.g., to cocaine, cyclosporine, or tacrolimus). Nevertheless,<unk>  should be suspected in patients presenting with systemic TMA, and appropriate diagnostic work-up should be undertaken. The neurological and kidney-related signs and symptoms of<unk>  overlap with those of TTP. However, unlike<unk> , TTP is primarily an autoimmune disorder in which the presence of an inhibitory autoantibody results in severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting, into smaller pieces. (TTP also can be a genetic disorder characterized by mutations in the ADAMTS13 gene leading to severe ADAMTS13 deficiency. This congenital cause of ADAMTS13 deficiency is called Upshaw-Schülman syndrome.) A lab test showing ADAMTS13 activity levels of ≤5% is indicative of TTP. Similarly, the gastrointestinal (GI) signs and symptoms of<unk>  overlap with those of STEC-HUS. Stool samples from patients with diarrhea or other GI symptoms should be tested for STEC and the presence of Shiga-toxin. However, a positive identification of Shiga-toxin, which is required to diagnose STEC-HUS, does not rule out<unk> . Nevertheless, in the appropriate clinical setting, a positive identification of Shiga-toxin makes<unk>  very unlikely.<unk>  patients report a mean timeline of 29 days for the overall diagnosis process from first noticing symptoms to receiving an<unk>  diagnosis. During which time they report their overall health state drops from 88% of patients feeling good to excellent, to 99% feeling good to very poor and a more than halving of their health status index from 3.8 (on a scale of 1 to 5) pre-illness to 1.4 at diagnosis.
Atypical hemolytic uremic syndrome
Thrombotic thrombocytopenic purpura
Hemolytic–uremic syndrome
Post-transfusion purpura
Severe fever with thrombocytopenia syndrome
Cold autoimmune hemolytic anemia
Transfusion-dependent anemia
Immune reconstitution inflammatory syndrome