Clinical Pathology: Hematology & Coagulation, Transfusion Medicine

• The laboratory studies show a microangiopathic hemolytic anemia (i.e., low hemoglobin, elevated reticulocytes, low haptoglobin, elevated bilirubin and lactate dehydrogenase (LDH), and schistocytes) and thrombocytopenia. In the absence of disseminated intravascular coagulation (DIC), the most likely diagnosis is thrombotic thrombocytopenic purpura (TTP).

• TTP is classically associated with a pentad of signs/symptoms: fever, mental status changes, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. However, all five findings may not be present in all cases.

• Congenital TTP is caused by an inherited deficiency of the ADAMTS13 enzyme. ADAMTS13 cleaves ultralarge multimers of von Willebrand factor (vWF). A deficiency in ADAMTS13 leads to an excess of ultralarge vWF multimers, platelet thrombi, and shear stress of red cells that leads to hemolysis. Simple plasma infusion can replace the enzyme in congenital TTP.

• Idiopathic TTP is caused by an autoantibody against ADAMTS13 that leads to its deficiency. Subsequently, ultralarge vWF multimers and platelet thrombi form, which causes hemolysis by the shearing of red cells. The treatment of choice in antibody-mediated TTP is plasmapheresis using fresh frozen plasma as the replacement fluid. This procedure removes the autoantibody from the circulation and provides ADAMTS13 in the plasma replacement fluid. Immunosupressants, usually steroids, are administered to inhibit antibody production.

• Drug-induced TTP is caused by multiple medications; cyclosporine, tacrolimus, clopidogrel, mitomycin C, and gemcitabine are the ones most commonly reported. Treatment requires the cessation of the medication inducing the TTP. Although plasmapheresis is often used, it may not be beneficial in drug-induced TTP.