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Authors:

Ihab Abumuhor, BS, MT (ASCP)

Ellen Hope Kearns, MS, SH(ASCP)H

Division of Health Sciences, School of Health, California State University Dominguez Hills, Carson, CA

Thrombotic Thrombocytopenic Purpura

Pathophysiology


The pathophysiology of TTP is still poorly understood. The current view includes endothelial cell damage and the presence of abnormally large molecular weight von Willebrand factor (vWF) multimers. In TTP, endothelial cell damage causes the release of ultra-large vWF multimers in the blood stream. These multimers increase platelets' adhesiveness and clumping. Normally these vWF multimers undergo proteolysis in the high-shear environment of the arterial circulation by the enzyme vWF metalloproteinase. Proteolysis reduces the size of polymers and inhibits their binding to platelet glycoprotein (GP) Ib/IX/V and GP IIb/IIIa receptors.

In chronic TTP, this enzyme is deficient or defective; in acute idiopathic TTP its action is inhibited by IgG antibodies. In both forms, large vWF polymers accumulate in the circulation, bind to platelet vWF receptors, and cause platelet aggregation responsible for the arterial ischemic symptoms characteristic of the disorder.

Ischemic symptoms may involve any organ, but central nervous system (CNS) involvement is especially common. The presentation may include anything from memory disturbance, behavioral irregularities, or headaches to coma. The partial occlusion causes fragmentation of erythrocytes and hemolysis. As the red cells break apart, high concentration of enzymes are released into the circulation in particular, serum LDH.

When endothelial cells are damaged throughout the body, platelets stick to the damaged areas and the platelet count may decrease to a very low level. Platelets can also stick to each other and block blood flow. At autopsy, hyaline thrombi are found in terminal arterioles and capillaries. The hyaline thrombi are composed of aggregated platelets and some fibrin polymers. Thrombi contain an abundance of vWF with little fibrinogen/fibrin, which is the opposite found in thrombi of disseminated intravascular coagulation.


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Last Update: September 11 2012