Treatment of Refractory Thrombotic Thrombocytopenic Purpura

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The summary below is from the full report titled "Remission of Chronic Thrombotic Thrombocytopenic Purpura after Treatment with Cyclophosphamide and Rituximab." It is in the 21 January 2003 issue of Annals of Internal Medicine (volume 138, pages 105-108). The authors are X Zheng, AM Pallera, LT Goodnough, JE Sadler, and MA Blinder.

What is the problem and what is known about it so far?

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but serious disease that can be fatal. Patients with TTP have low numbers of platelets (thrombocytopenia), abnormal red cells, and a tendency to develop tiny clots (thrombi) in small blood vessels. In some adults, TTP is caused by an immune reaction. Their bodies make an antibody that inactivates an important protein (ADAMTS13) whose function is to prevent platelets from sticking together and plugging blood vessels.

Patients with TTP may have easy bruising, rashes with many little dots or large purple patches (purpura), fever, belly pain, thrombi in the brain or kidneys, or bleeding due to few platelets. Treatments include plasma exchanges to help rid the body of antibodies, removal of the spleen to reduce excess destruction of platelets, and drugs that suppress autoimmune processes. However, some patients have refractory TTP despite standard treatments. Whether intensive immunotherapy aimed at markedly suppressing antibodies against ADAMTS13 will help them is not known.

Why did the researchers do this particular study?

To see whether intensive immunotherapy works for refractory TTP.

Who was studied?

A 42-year-old woman with chronic relapsing TTP despite many treatments.

How was the study done?

The patient was treated with traditional therapies, including plasma exchange, removal of the spleen, and some immunotherapy (prednisone, vincristine, cyclosporine) for 19 months. She had many relapses despite treatment. Over the following year, the researchers twice treated relapses with powerful intensive immunotherapy administered through the patient's veins (rituximab or rituximab plus cyclophosphamide). The researchers repeatedly measured levels of ADAMTS13 and tested for inhibitors of ADAMTS13.

What did the researchers find?

After the second course of intensive immunotherapy, the patient had no symptoms of TTP and had normal numbers of platelets. Levels of ADAMTS13, which had been low to nonexistent before intensive immunotherapy, normalized. An IgG inhibitor, which had been present before intensive immunotherapy, was no longer detectable. The patient has not needed any additional therapy for 6 months.

What were the limitations of the study?

The study involved one patient and did not directly compare benefits of intensive immunotherapy with standard therapy.

What are the implications of the study?

Intensive immunotherapy may be a promising therapy for adults with refractory TTP. However, we need observations in many more patients and results from controlled studies that directly compare it with other therapies before we routinely recommend it.