Thrombotic Thrombocytopenic Purpura (TTP)

Epidemiology and Etiology:

• Thrombotic microangiopathy
• Overlapping features with hemolytic uremic syndrome (HUS)
• Adults primarily
• Blacks more common
• obesity
• Idiopathic or secondary:
• Pregnancy
• Verotoxin (ex. E. coli and Shigella dysenteriae)
• Malignancy, exp. metastatic carcinoma
• Drug-induced –
• chemotherapy agents
• Immunosuppressive agents
• Post-marrow/stem cell transplantation
• Failure to cleave large von Willebrand factor (vWF) multimers
• Autoantibodies to ADAMTS 13
• Mutations of ADAMTS 13 gene (rare congenital / familial form)

Common sites:

Gross features:

Microscopic features:

• PBF:
• Polychromasia and other evidence of hemolysis
• Red cell fragments (characteristic)
• Thrombocytopenia
• Small vessel platelet thrombi

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

• More than 50 germline mutations of ADAMTS 13 gene have been described (rare)

Other features:

• Anemia (Hgb 80-90)
• Classic pentad:
• Profound thrombocytopenia
• Microangiopathic hemolysis
• Neurologic symptoms and signs (typically fluctuating)
• Renal function abnormalities
• Fever
• Variable signs and symptoms of organ ischemia
• LDH elevated
• Clotting tests normal generally (occasionally DIC features)
• Creatinine elevated in one third (renal failure uncommon)

References:

• Porwit A, McCullough J, Erber WN. Blood and bone marrow pathology (2011)