What is the underlying cause of thrombotic thrombocytopenic purpura (TTP)?

Thrombotic thrombocytopenic purpura (TTP) is primarily caused by a deficiency in ADAMTS13, a von Willebrand factor cleaving protease. This enzyme is crucial for regulating the size of von Willebrand factor (vWF) multimers in the blood. When the activity of ADAMTS13 is significantly impaired, either due to inherited mutations or the formation of inhibitory antibodies against the enzyme, large, dysfunctional vWF multimers accumulate. These oversized multimers lead to increased platelet aggregation and the formation of microthrombi within the small blood vessels.

This process results in thrombocytopenia (due to the consumption of platelets in thrombus formation), microangiopathic hemolytic anemia, and organ damage due to reduced blood flow. Recognizing the central role of ADAMTS13 provides insight into the pathophysiology of TTP and underlines the importance of this protease in maintaining normal hemostatic balance. In summary, a deficiency in ADAMTS13 is the key change that leads to the cascade of events characterizing TTP.