hematology and oncology
Thrombotic Thrombocytopenic Purpura (TTP)
Etiology of TTP
Thrombotic thrombocytopenic purpura (TTP) is caused by Congenital or acquired deficient activity of the plasma enzymeADAMTS13 TheADAMTS13enzyme is a plasma protease that cleavesvon Willebrand factorinto smaller sizes and thereby eliminates unusually largevon Willebrand factor(VWF) multimers that would otherwise accumulate on endothelial cells where they can cause platelet thrombi.ADAMTS13activity usually has to be < 10% of normal for disease to manifest. Other prothrombotic factors may also need to be present. Most cases are acquired and involve development of an autoantibody againstADAMTS13. Rare cases are hereditary (Upshaw-Schulman syndrome), involving an autosomal recessive mutation of theADAMTS13gene. In many acquired cases, the cause of the autoantibody is unknown. Known causes and associations include Female sex Black ethnicity Use ofdesmopressin Pregnancy (TTP is often indistinguishable from severe Preeclampsia and Eclampsia ) Thrombotic microangiopathy similar to that of TTP can be triggered by a number of drugs, includingquinine,cyclosporine,tacrolimus, and cancer chemotherapy drugs (eg,mitomycinC,gemcitabine). In most cases, the drugs are thought to damage small vessels and cause microthrombi. Unlike with TTP, such patients invariably have normal levels of ADAMTS 13 and do not respond to plasma exchange, corticosteroids or complement inhibition. 