History and exam

Key diagnostic factors

common

nonspecific prodrome

Median time of symptom onset to diagnosis is 1 week.[44]

severe neurologic symptoms (coma, focal abnormalities, seizures)

Approximate prevalence 45%.[18]

uncommon

mild neurologic symptoms (headache, confusion)

Approximate prevalence 14%.[18]

fever

Approximate prevalence 20%.[44]

Other diagnostic factors

common

age 30 to 50 years

Most patients with TTP subsequent to severe von Willebrand factor cleaving enzyme (ADAMTS-13) deficiency are between the ages of 20 and 59 years.[17] Another source reports an average age of 39 years (range, 19 to 71 years).[18]

digestive symptoms (nausea, vomiting, diarrhea, abdominal pain)

These symptoms can be secondary to microthrombi in the bowel. If hemolytic uremic syndrome is included in analysis, diarrhea can be related to Escherichia coli infection. Approximate prevalence 54%.[18]

uncommon

weakness

Approximate prevalence 20%.[44]

bleeding symptoms (purpura, ecchymosis, menorrhagia)

Approximate prevalence 20%.[44]

Risk factors

strong

black ethnicity

The relative incidence among black people is ninefold that of nonblack people.[17] Forty-four percent of patients with TTP are black.[17][29]

female gender

Between 65% and 75% of patients with TTP are women.[17]

obesity

Evaluation of 105 patients with classic TTP demonstrated that marked obesity was a risk factor for TTP, associated with an odds ratio of 7.6.[30] Of patients, 55% have a BMI >30 kg/m².[29]

pregnancy (near term or postpartum period)

TTP is diagnosed during pregnancy or postpartum in 12% to 25% of cases, with 75% of these episodes occurring around the time of delivery.[31]

cancer therapies

TTP develops in <1% of patients receiving mitomycin.[32] Associations have also been seen with cyclosporine, gemcitabine, and tacrolimus.[33][34]

There have been reports of thrombotic microangiopathy associated with the use of targeted cancer agents (e.g., immunotoxins, monoclonal antibodies, tyrosine kinase inhibitors).[28]

weak

HIV infection

A small study demonstrated an odds ratio of 30 to 35.[35]

bone marrow transplantation

This subtype responds poorly to conventional treatment.[36]

antiplatelet agents

Clopidogrel has been implicated as a cause in 1 per 1600 to 5000 patients treated.[37] Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to von Willebrand factor cleaving enzyme (ADAMTS-13) metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE.[38]

quinine

In a case study of 123 patients, 11% of cases were associated with quinine use.[39]

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