Thrombotic+thrombocytopenic+purpura+(TTP)


 * Thrombotic Thrombocytopenic Purpura (TTP) **

**What is TTP?**

Thrombotic thrombocytopenic purpura is a rare blood disorder that affects the blood. Blood clots, called thrombi, form in small blood vessels. The clots are formed from clumps of platelets, cell fragments that are used in blood clotting. Since so many platelets are used to form the clots, there are not as many platelets in the blood stream. The reduced amount of platelets is called thrombocytopenia. An affect of thrombocytopenia is purpura, which are purple spots from bleeding under the skin.  //Here are a few of the problems associated with blood clots:// -headaches -confusion/ slurred speech -abdominal pain -abnormal kidney function -fever -heart problems

Another issue with TTP is the hemolysis of red blood cells prematurely. Because of the blood clots, some of the red blood cells are destroyed faster than they can be replaced. This is known as hemolytic anemia.

//Some symptoms of hemolytic anemia are:// -paleness -jaundice -fatigue -a rapid heart rate


 * How is it inherited?**

TTP is autosomal recessive. Typically parents are carriers and each carry the recessive gene. In a normal person the gene, ADAMTS13 gives the instructions for the production of the enzyme involved in blood clotting, but in people with TTP mutations in ADAMTS13 have disruptions. ADAMTS13 is a parts of the ADAMTS family of zinc metalloproteinase genes. Pedigrees and genome-wide linkage analysis have discovered 12 mutations of this gene, which accounts for 14 of the 15 alleles studied. ADAMTS13 is a gene that spans 29 exons encompassing 37 kb in the human genome and encodes a protein with 1,427 amino acids. The analysis of DNA has shown that the splicing of exon 17 results in a frameshift mutation giving a truncated 842-amino-acid form of the protein. This means that there could be differentially regulatied alternative isoforms of ADAMTS13 with diverse biological functions as well as the putative proteolytic processing of the von Willebrand factor. Two out of twelve of the mutations are frameshifts. One is an insertion. The rest are all nonconservative amino-acid substitutions. These mutations occur on chromosome 9.  The von Willebrand factor is the protein involved in blood clotting and is decreased in people with TTP, the multimeric forms of it, however, are in an unusually large amount. It is thought to have a pathogenic role in the formation of microvascular von Willebrand factor. The von Willebrand-cleaving protease activity (VWF) is a semidominant trait.

The origin of TTP is not exactly known, but it has been thought that recent common ancestry may be a factor. In one study the parents of the affected people were all from the same villages where their families have lived for generations.  -fever -thrombocytopenia -microangiopathic hemolytic anemia -fluctuating neurological impairment -renal dysfunction -purpura -fatigue -strokes
 * Symptoms/ Effects:**

TTP can be confused with other disorders because of its rarity. It is often mistaken in children as hemolytic uremic syndrome (HUS) because it is phenotypically similar. With TTP, episodes are sporadic. Until recently TTP was unheard of by many doctors, so patients were typically misdiagnosed. In families, siblings are often affected.
 * Diagnosis:**

TTP can be controlled. As long as it is monitored and treated, patients usually lead pretty normal lives. For each person it is different because TTP occurs in episodes. Every once and a while a person may have a really bad episode, which can lead to hospitalization. They can get very sick and they get bruised very easily. TTP does not typically mean death unless it is left untreated and even then it may not affect the person too much. TTP can increase the intensity of other illnesses, which is very dangerous. TTP can also be a factor in strokes as well.
 * Prognosis:**

Blood transfusions of fresh-frozen plasma (FFP) or cryosupernatant plasma are typically what doctors prescribe. People with TTP normally visit a Hematologist who makes sure their blood is tested in the lab. Platelet levels are counted to determine if a blood transfusion is necessary. The time in between transfusions vary. Some doctors have their patients get transfusions every month, others have them get it whenever their counts are low. A few of the many leading doctors in TTP research are David Ginsburg, Jefferson D. Upshaw, and Han-Mou Tsai. Dr. Tsai is currently as Hershey Medical center and is taking action in the research and treatment of patients with TTP. There is no cure for TTP.
 * Treatment:**

From 1988-1991 TTP incidence in the U.S. was estimated to be 3.7 cases per 1 million residents. It is also estimated that TTP affects 4 to 7 million people each year in the U.S., but in the familial or the genetic form, it is a lot less common.  **__Bibliography:__** "Genetics of a clotting disease." Nature. __International Weekly Journal of Science__ 413. 4 Oct. 2001:488-494. Website: www.nature.com
 * Statistics:**

"Hemostasis, Thrombosis, and Vascular Biology." __Blood__ 100. 15 Nov. 2002.

Thrombotic thrombocytopenic purpura: Genetic Home Reference []

Pedigree pic. [] DNA pic. [] First ADAMTS13 pic. [] Second ADAMSTS13 pic. [] Platelet pic. [] Von Williebrand picture --