Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.
Thrombotic thrombocytopenic purpura (TTP or Moschcowitz disease) is a rare disorder of the blood-coagulation system, causing extensive microscopic blood clots to form in the small blood vessels throughout the body (thrombotic microangiopathy).[1][2] Most cases of TTP arise from deficiency or inhibition of the enzyme ADAMTS13, which is responsible for cleaving large multimers of von Willebrand factor (vWF).[3] Red blood cells passing the microscopic clots are subjected to shear stress which leads to hemolysis. Reduced blood flow and cellular injury results in end organ damage. Current therapy is based on support and plasmapheresis to reduce circulating antibodies against ADAMTS13 and replenish blood levels of the enzyme.[3]
Classically, the following five features (“pentad”) are indicative of TTP;[4] in most cases, some of these are absent.[2]
A patient may notice dark urine from the hemolytic anemia. Because of the many small areas of ischemia produced by clots in the microvasculature, symptoms may be diffuse and fluctuating, including the classical bruising, confusion, or headache, but also nausea and vomiting (from ischemia in the GI tract or from central nervous system involvement), chest pain from cardiac ischemia, seizures, muscle and joint pain, etc.[citation needed].
TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by spontaneous aggregation of platelets and activation of coagulation in the small blood vessels. Platelets are consumed in the coagulation process, and bind fibrin, the end product of the coagulation pathway. These platelet-fibrin complexes form microthrombi which circulate in the vasculature and cause shearing of red blood cells, resulting in hemolysis.[2]
Roughly, there are two forms of TTP: idiopathic and secondary TTP. A special case is the inherited deficiency of ADAMTS13, known as the Upshaw-Schulman syndrome.[2]
The idiopathic form of TTP was recently linked to the inhibition of the enzyme ADAMTS13 by antibodies, rendering TTP an autoimmune disease. ADAMTS13 is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets, blood clots, and the blood vessel wall in the process of blood coagulation. Very large vWF molecules are more prone to lead to coagulation. Hence, without proper cleavage of vWF by ADAMTS13, coagulation occurs at a higher rate, especially in the part of the blood vessel system where vWF is most active due to high shear stress: in the microvasculature.[3]
In idiopathic TTP, severely decreased (<5% of normal) ADAMTS13 activity can be detected in most (80%) patients, and inhibitors are often found in this subgroup (44-56%). The relationship of reduced ADAMTS13 to the pathogenesis of TTP is known as the Furlan-Tsai hypothesis, after the two independent groups of researchers who published their research in the same issue of the New England Journal of Medicine in 1998.[5][6][7] This theory is seen as insufficient to explain the etiology of TTP, since many patients with hereditary lack of ADAMTS13 activity do not manifest clinical symptoms of TTP.[citation needed] [tubepress mode=’tag’, tagValue=’Thrombotic thrombocytopenic purpura’]