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Thrombotic thrombocytopenic purpura

Reviewed October 2008

What is thrombotic thrombocytopenic purpura?

Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart. Resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems.

Blood clots normally form to prevent excess blood loss at the site of an injury. In people with thrombotic thrombocytopenic purpura, clots develop in blood vessels even in the absence of injury. Blood clots are formed from clumps of cell fragments called platelets, which circulate in the blood and assist with clotting. Because a large number of platelets are used to make clots in people with thrombotic thrombocytopenic purpura, fewer platelets are available in the bloodstream. A reduced level of circulating platelets is known as thrombocytopenia. Thrombocytopenia can lead to small areas of bleeding just under the surface of the skin, resulting in purplish spots called purpura.

This disorder also causes red blood cells to break down (undergo hemolysis) prematurely. As blood squeezes past clots within blood vessels, red blood cells can break apart. A condition called hemolytic anemia occurs when red blood cells are destroyed faster than the body can replace them. This type of anemia leads to paleness, yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate.

There are two major forms of thrombotic thrombocytopenic purpura, an acquired (noninherited) form and a familial form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single episode of signs and symptoms, or they may recur over time. The familial form of this disorder is much rarer and typically appears in infancy or early childhood. In people with the familial form, signs and symptoms often recur on a regular basis.

How common is thrombotic thrombocytopenic purpura?

The precise incidence of thrombotic thrombocytopenic purpura is unknown. Researchers estimate that, depending on geographic location, the condition affects 1.7 to 11 per million people each year in the United States. For unknown reasons, the disorder occurs more frequently in women than in men. The acquired form of thrombotic thrombocytopenic purpura is much more common than the familial form.

What genes are related to thrombotic thrombocytopenic purpura?

Mutations in the ADAMTS13 gene cause the familial form of thrombotic thrombocytopenic purpura. The ADAMTS13 gene provides instructions for making an enzyme that is involved in the normal process of blood clotting. Mutations in this gene lead to a severe reduction in the activity of this enzyme. The acquired form of thrombotic thrombocytopenic purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not have mutations in the ADAMTS13 gene. Instead, their immune systems often produce specific proteins called autoantibodies that block the activity of the enzyme.

A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. Normally, blood clots form at the site of an injury to seal off damaged blood vessels and prevent excess blood loss. In people with thrombotic thrombocytopenic purpura, clots form throughout the body as platelets bind together abnormally and stick to the walls of blood vessels. These clots can block small blood vessels, causing organ damage and the other features of thrombotic thrombocytopenic purpura.

Researchers believe that other genetic or environmental factors may contribute to the signs and symptoms of thrombotic thrombocytopenic purpura. In people with reduced ADAMTS13 enzyme activity, factors such as pregnancy, surgery, and infection may trigger abnormal blood clotting and its associated complications.

Related Gene(s)

Changes in this gene are associated with thrombotic thrombocytopenic purpura.

  • ADAMTS13

How do people inherit thrombotic thrombocytopenic purpura?

The familial form of thrombotic thrombocytopenic purpura is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

The acquired form of thrombotic thrombocytopenic purpura is not inherited.

Where can I find information about diagnosis or management of thrombotic thrombocytopenic purpura?

These resources address the diagnosis or management of thrombotic thrombocytopenic purpura and may include treatment providers.

  • Genetic Testing Registry: Upshaw-Schulman syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1268935)
  • MedlinePlus Encyclopedia: Blood Clots (http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm)
  • MedlinePlus Encyclopedia: Hemolytic anemia (http://www.nlm.nih.gov/medlineplus/ency/article/000571.htm)
  • MedlinePlus Encyclopedia: Purpura (http://www.nlm.nih.gov/medlineplus/ency/article/003232.htm)
  • MedlinePlus Encyclopedia: Thrombocytopenia (http://www.nlm.nih.gov/medlineplus/ency/article/000586.htm)
  • MedlinePlus Encyclopedia: Thrombotic thrombocytopenic purpura (http://www.nlm.nih.gov/medlineplus/ency/article/000552.htm)

You might also find information on the diagnosis or management of thrombotic thrombocytopenic purpura in Educational resources (http://www.ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about thrombotic thrombocytopenic purpura?

You may find the following resources about thrombotic thrombocytopenic purpura helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for thrombotic thrombocytopenic purpura?

  • Familial Thrombotic Thrombocytopenia Purpura
  • Microangiopathic hemolytic anemia
  • Moschkowitz Disease
  • Purpura, Thrombotic Thrombocytopenic
  • Thrombotic microangiopathy, familial
  • TTP

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about thrombotic thrombocytopenic purpura?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding thrombotic thrombocytopenic purpura?

anemia ; autosomal ; autosomal recessive ; blood clotting ; cell ; clotting ; enzyme ; familial ; fever ; gene ; hemolysis ; hemolytic anemia ; incidence ; infection ; inherited ; injury ; jaundice ; kidney ; neurological ; platelets ; purpura ; recessive ; surgery ; syndrome ; thrombocytopenia

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Crowther MA, George JN. Thrombotic thrombocytopenic purpura: 2008 update. Cleve Clin J Med. 2008 May;75(5):369-75. (http://www.ncbi.nlm.nih.gov/pubmed/18556880?dopt=Abstract)
  • George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med. 2006 May 4;354(18):1927-35. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16672704?dopt=Abstract)
  • Kremer Hovinga JA, Studt JD, Lämmle B. The von Willebrand factor-cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP). Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):417-21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15692254?dopt=Abstract)
  • Kwaan HC, Boggio LN. The clinical spectrum of thrombotic thrombocytopenic purpura. Semin Thromb Hemost. 2005 Dec;31(6):673-80. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16388418?dopt=Abstract)
  • Lian EC. Pathogenesis of thrombotic thrombocytopenic purpura: ADAMTS13 deficiency and beyond. Semin Thromb Hemost. 2005 Dec;31(6):625-32. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16388413?dopt=Abstract)
  • Sadler JE, Moake JL, Miyata T, George JN. Recent advances in thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2004:407-23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15561695?dopt=Abstract)
  • Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol. 2003 Apr;14(4):1072-81. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12660343?dopt=Abstract)
  • Tsai HM. Current concepts in thrombotic thrombocytopenic purpura. Annu Rev Med. 2006;57:419-36. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16409158?dopt=Abstract)
  • Tsai HM. Is severe deficiency of ADAMTS-13 specific for thrombotic thrombocytopenic purpura? Yes. J Thromb Haemost. 2003 Apr;1(4):625-31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12871390?dopt=Abstract)
  • Tsai HM. Molecular mechanisms in thrombotic thrombocytopenic purpura. Semin Thromb Hemost. 2004 Oct;30(5):549-57. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15497097?dopt=Abstract)
  • Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int. 2006 Jul;70(1):16-23. Epub 2006 May 31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16760911?dopt=Abstract)
  • Tsai HM. Thrombotic thrombocytopenic purpura: a thrombotic disorder caused by ADAMTS13 deficiency. Hematol Oncol Clin North Am. 2007 Aug;21(4):609-32, v. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17666281?dopt=Abstract)
  • Yarranton H, Machin SJ. An update on the pathogenesis and management of acquired thrombotic thrombocytopenic purpura. Curr Opin Neurol. 2003 Jun;16(3):367-73. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12858075?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2008
Published: November 24, 2014