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Mechanisms of Thrombotic Thrombocytopenic Purpura (TTP), a Complication Associated with the Drug Ticlopidine FREE

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The summary below is from the full report titled “Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura.” It is in the 16 May 2000 issue of Annals of Internal Medicine (volume 132, pages 794-799). The authors are H.-M. Tsai, L. Rice, R. Sarode, T.W. Chow, and J.L. Moake.

Ann Intern Med. 2000;132(10):794. doi:10.7326/0003-4819-132-10-200005160-00039
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What is the problem and what is known about it so far?

Ticlopidine is a drug that acts on platelets, the tiny cells in the bloodstream that help blood to clot. Ticlopidine is therefore sometimes used to reduce the risk for strokes by preventing clotting in patients whose arteries leading to the brain are greatly narrowed. It is also used to prevent clots from blocking cardiac stents (tunnel-like devices that are sometimes used to open narrowed blood vessels in the heart), thus cutting down the risk of heart attacks. Thrombotic thrombocytopenic purpura (TTP) is a medical condition that can occur on its own, but it has also been reported as a side effect of ticlopidine. TTP, a potentially serious and sometimes fatal illness, includes kidney problems, fever, bleeding, confusion, and seizures. It is not known how ticlopidine leads to TTP. However, in cases of TTP not related to a drug, a substance found normally in the bloodstream that helps blood to clot (called von Willebrand factor) is involved.

Why did the researchers do this particular study?

To see whether von Willebrand factor is one of the factors that helps to cause TTP when this condition occurs as a harmful side effect of ticlopidine therapy.

Who was studied?

Seven patients who developed TTP 2 to 7 weeks after they began taking ticlopidine. For comparison, the researchers also studied patients in two control groups: 7 patients who had taken ticlopidine for 3 to 5 weeks but had not developed TTP, and 10 hospitalized patients selected at random.

How was the study done?

The researchers measured von Willebrand factor and tested its activity in blood samples of the patients with TTP and the control patients. The patients who developed TTP received standard treatment for this condition, which included stopping the ticlopidine therapy.

What did the researchers find?

The patients with ticlopidine-associated TTP had abnormalities of von Willebrand factor that were not present in the control patients. These abnormalities were similar to the abnormalities previous researchers have found in patients with the form of TTP not related to a drug. All of the TTP patients recovered.

What were the limitations of the study?

The number of patients in this study was very small, and these patients may not be typical of all patients with drug-related TTP. It will be important to do additional studies of patients with ticlopidine-related TTP in order to understand more fully why this complication develops in some patients taking the drug but not in others.

What are the implications of the study?

Problems with von Willebrand factor appear to occur in the type of TTP associated with ticlopidine, just as they do when TTP is not related to drugs.





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