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The exact cause of TTP is unknown, but a number of underlying factors have been identified. Under normal circumstances, a blood protein known as Von Willebrand factor (VWf) is produced by endothelial cells, which line the insides of arteries. VWf is an important part of the blood-clotting cascade and helps platelets gather at the site of a wound. Typically, VWf is released into the blood stream in large structures known as "unusually large von Willebrand factor." Once in the blood, these large structures are reduced in size by a substance known as ADAMTS13. Among people with TTP, however, there is a deficiency in ADAMTS13, meaning that these large VWf structures stay intact. This is thought to encourage inappropriate blood clotting when these structures attach to blood platelets.
While this appears to be a leading factor in TTP, there are several other mechanisms that have been identified. Many patients with TPP have high levels of an autoantibody to ADAMTS13. This means that the immune system has identified ADAMTS13 as a foreign invader and is attacking and destroying it. This finding is especially common among people with TTP due to unknown causes, or idiopathic TTP. In these cases, TTP may be an autoimmune disease in which the body mistakenly identifies normal cells (e.g., ADAMTS13) as invaders and attacks and destroys them.
Additional theories that may explain TTP include endothelial injury, possibly caused by a drug, which causes platelet aggregation, and the shiga toxin, which is released during infection with the E. coli and other bacteria.
Whatever the underlying cause, there are certain populations that seem more vulnerable to TTP. Among women, it may be triggered by pregnancy or by the use of estrogen (e.g., birth control pills). TTP has also been associated with HIV (the virus that causes AIDS), as well as toxins associated with spider and bee venoms (in rare cases). In rare cases, TPP occurs after cardiovascular surgery, especially coronary artery surgery.
There are also several drugs that have been linked to TTP. These include:
- Certain anticoagulants, including ticlopidine and, to a lesser extent, clopidogrel. Ticlopidine was commonly prescribed for people who just had a heart attack, stroke, mini-stroke, balloon angioplasty or stenting procedure. Although designed to help prevent the formation of blood clots, ticlopidine was linked in a number of studies done on people who developed TTP within a month after beginning ticlopidine therapy. It is estimated that TTP developed in between one out of every 1,600 patients and one out of every 4,800 who took ticlopidine. In response to the higher risk of TTP, clopidogrel has been developed. Although it appears to be safer than ticlopidine, researchers have still found a link between taking clopidogrel and the development of TTP in a small number of people.
- Quinine. This over-the-counter medication is used to treat muscle cramps and is the most common cause of drug-induced TTP.
- Cancer-fighting chemotherapy drugs. TTP has been associated with four chemotherapy regimens: mitomycin C, cisplatin, gemcitabine, and the use of radiation and high-dose chemotherapy prior to bone marrow cell transplantation.
- Cyclosporine. This medication is designed to suppress the immune system. It is throught to cause TPP through direct endothelial injury and enhanced platelet aggregation. In most cases, the TTP will resolve if the medication is discontinued.
The diagnosis begins with the physician taking the patient’s complete medical history and then giving the patient a physical examination. The physician will also run blood tests to determine if there has been a reduction of platelets in the blood. The majority of patients will show this reduction of platelets, neurological changes (e.g., confusion) and anemia (a low red blood cell count).
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