[1] This results in decreased break down of large multimers of von Willebrand factor (vWF) into smaller units.

These are:[3] TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in the small blood vessels.

[19][20] People with this inherited ADAMTS13 deficiency have a surprisingly mild phenotype, but develop TTP in clinical situations with increased von Willebrand factor levels (e.g. infection).

[22][23] A 2024 study suggested that hereditary TTP is underdiagnosed and should be considered in cases of unexplained stroke, neonatal jaundice, and severe pre-eclampsia.

Probable etiology may involve, at least in some cases, endothelial damage,[26] although the formation of thrombi resulting in vessel occlusion may not be essential in the pathogenesis of secondary TTP.

[27] These factors may also be considered a form of secondary aHUS; people presenting with these features are, therefore, potential candidates for anticomplement therapy.

The underlying mechanism typically involves autoantibody-mediated inhibition of the enzyme ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand factor (vWF) into smaller units.

[29] Thrombotic thrombocytopenic purpura (TTP) initially presents with a range of symptoms that may include severe thrombocytopenia (platelet count usually < 30,000/mm³), microangiopathic hemolytic anemia (evidenced by schistocytes in the blood smear), and various clinical signs such as petechiae, purpura, neurologic symptoms, myocardial ischemia, mesenteric ischemia, and renal abnormalities.

Notably, the complete classic pentad of TTP symptoms—microangiopathic hemolytic anemia, thrombocytopenia, renal abnormalities, fever, and neurologic abnormalities—is only seen in about 10% of acute cases at initial presentation.

[30] Clinical suspicion of TTP is often established with an initial emergent presentation of one or more classic symptoms and a complete blood count revealing severe thrombocytopenia.

[35] A definitive diagnosis of TTP may be established when a laboratory assay of ADAMTS13 identifies under 10% of normal enzyme function.

[28] ADAMTS13 levels above 5%, coupled with a positive test for shiga-toxin/enterohemorrhagic E. coli (EHEC), are more likely indicative of HUS,[42] whereas absence of shiga-toxin/EHEC can confirm a diagnosis of aHUS.

If apheresis is not available, fresh frozen plasma can be infused, but the volume that can be given safely is limited due to the danger of fluid overload.

[44] Rituximab, a monoclonal antibody aimed at the CD20 molecule on B lymphocytes, may be used on diagnosis; this is thought to kill the B cells and thereby reduce the production of the inhibitor.

[44] Caplacizumab is an adjunct option in treating TTP as it has been shown that it induces a faster disease resolution compared with those people who were on placebo.

[50] The ISTH guidelines[51] recommended for first acute episode and relapses of immune-mediated TTP (iTTP), add corticosteroids to therapeutic plasma exchange (TPE) and consider adding rituximab and caplacizumab.

People with refractory or relapsing TTP may receive additional immunosuppressive therapy, e.g. vincristine, cyclophosphamide, cyclosporine A, or splenectomy.

[3][45] Children with Upshaw-Schulman syndrome receive prophylactic plasma every two to three weeks; this maintains adequate levels of functioning ADAMTS13.

[52] Measurements of blood levels of lactate dehydrogenase, platelets, and schistocytes are used to monitor disease progression or remission.

[56] The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for people with idiopathic TTP diagnosed and treated early with plasmapheresis.

[58] Idiopathic TTP occurs more often in women as well as people of African descent, and TTP secondary to autoimmune disorders such as systemic lupus erythematosus occurs more frequently in people of African descent, although other secondary forms do not show this distribution.

Moschcowitz noted his patient, a 16-year-old girl, had anemia, small and large bruises, microscopic hematuria, and, at autopsy, disseminated microvascular thrombi.

[63] In 1966, a review of 16 new cases and 255 previously reported cases led to the formulation of the classical pentad of symptoms and findings (i.e., thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, kidney failure, fever); in this series, mortality rates were found to be very high (90%).