Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body.Most cases of TTP arise from inhibition of the enzyme ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand factor (vWF) into smaller units. A rarer form of TTP, called Upshaw-Schülman syndrome, is genetically inherited as a dysfunction of ADAMTS13. If large vWF multimers persist there is tendency for increased coagulation.
Red blood cells passing the microscopic clots are subjected to shear stress which damages their membranes, leading to intravascular hemolysis and schistocyte formation. Reduced blood flow due to thrombosis and cellular injury results in end organ damage.
Classically, the following five features are indicative of TTP in most cases, some of these are absent.
* Neurologic symptoms (fluctuating), such as hallucinations, bizarre behavior, altered mental status, stroke or headaches
* Kidney failure
* Thrombocytopenia leading to bruising or purpura
* Microangiopathic hemolytic anemia
Since the early 1990s, plasmapheresis has become the treatment of choice for TTP. This is an exchange transfusion involving removal of the patient's blood plasma through apheresis and replacement with donor plasma (fresh frozen plasma or cryosupernatant); the procedure has to be repeated daily to eliminate the inhibitor and abate the symptoms. If pheresis is not available, fresh frozen plasma can be infused, but the volume able to be given safely is limited due to the danger of fluid overload. Lactate dehydrogenase levels are generally used to monitor disease activity.