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Glanzmann Thrombasthenia

NORD is very grateful to Barry S. Coller, MD, David Rockefeller Professor of Medicine; Head, Allen and Frances Adler Laboratory of Blood and Vascular Diseases, The Rockefeller University, for assistance in the preparation of this report.

Synonyms of Glanzmann Thrombasthenia

  • diacyclothrombopathia IIb-IIIa
  • Glanzmann disease
  • Glanzmann-Naegeli syndrome
  • Glanzmann thrombasthenia
  • Glanzmann thrombasthenia, type A
  • glycoprotein complex IIb/IIIa, deficiency of
  • GP IIb-IIIa complex, deficiency of
  • GTA
  • platelet fibrinogen receptor deficiency
  • thrombasthenia
  • thrombasthenia of Glanzmann and Naegeli

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Glanzmann thrombasthenia (GT) is a rare inherited blood clotting (coagulation) disorder characterized by the impaired function of specialized cells (platelets) that are essential for proper blood clotting. Symptoms of this disorder usually include abnormal bleeding, which may be severe. Prolonged untreated or unsuccessfully treated hemorrhaging associated with Glanzmann thrombasthenia may be life threatening.

Symptoms

The symptoms of Glanzmann thrombasthenia usually begin at birth or shortly thereafter and include the tendency to bleed easily and sometimes profusely, especially after surgical procedures. Other symptoms may include susceptibility to easy bruising, nosebleeds (epistaxis), bleeding from the gums (gingival), intermittent gastrointestinal bleeding, and/or variably large red or purple colored spots on the skin that are caused by bleeding in the skin. Women with GT often also have unusually heavy menstrual bleeding and irregular uterine bleeding. Rarely, internal bleeding and blood in the urine (hematuria) can occur. The severity of the symptoms varies greatly. Some affected individuals have mild bruising and others have severe hemorrhages that can be life threatening.

Causes

Glanzmann thrombasthenia is inherited as an autosomal recessive genetic trait. An abnormality in one or the other genes for the platelet alpha-IIbß3 (GPIIb/IIIa) receptor prevents platelets from forming a plug when bleeding occurs. The genes for the receptor proteins alpha-IIb (glycoprotein IIb; GPIIb) and ß3 (glycoprotein IIIa; GPIIIa) are located on the long arm of chromosome 17 (17q21.32). Many different abnormalities in these genes have been identified.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. This is true for carriers of Glanzmann thrombasthenia. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive the normal genes from both parents and therefore be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Affected Populations

Glanzmann thrombasthenia is a rare disorder that affects males and females in equal numbers. The symptoms of this disease are usually apparent at birth (neonates) or during infancy. Approximately 200 cases have been reported. This condition occurs with greater frequency in populations in which intermarriage within a group (consanguinity) is more prevalent such as in some regions of the Middle East, India, and France.

Related Disorders

Symptoms of other disorders listed below can be similar to those of Glanzmann thrombasthenia. Comparisons may be useful for a differential diagnosis:

Hemophilia is a rare inherited blood clotting (coagulation) disorder caused by an inactive or deficient blood protein, usually factor VIII or IX both of which are needed for normal blood clotting. Factors VIII and IX are two of several proteins that enables the blood to clot. Hemophilia is found in males almost exclusively and can be classified as mild, moderate, or severe. The most serious symptom of hemophilia is uncontrolled internal bleeding that may begin spontaneously without any apparent cause. Internal bleeding may cause permanent damage to the joints and muscles. People with hemophilia bleed for a longer period of time than people who have the normal amount of active clotting factors in their blood. Bruises and trauma can trigger episodes of serious internal bleeding in people with this disorder. (For more information on this disorder, choose "hemophilia" as your search term in the Rare Disease Database.)

Bernard-Soulier syndrome is a rare inherited blood clotting (coagulation) disorder characterized by abnormalities of platelets, including large platelets that do not adhere normally to damaged blood vessels because of an abnormal Glycoprotein Ib-IX-V complex. Symptoms include a tendency to bleed excessively and bruise easily. People with Bernard-Soulier syndrome tend to bleed profusely from cuts and other injuries. Nosebleeds and unusually heavy menstrual flow are also common. Bleeding into the skin may cause small or large purple colored spots (purpura) in different areas of the body. (For more information on this disorder, choose "Bernard-Soulier" as your search term in the Rare Disease Database.)

May-Hegglin syndrome is a rare inherited disorder of blood platelets and certain white blood cells characterized by reduced numbers of abnormally large platelets. Patients usually do not bleed excessively unless they have very low platelet counts.(For more information on this disorder, choose "May-Hegglin" as your search term in the Rare Disease Database.)

Storage pool disease (SPD) is a rare inherited disorder of blood platelets characterized by clotting dysfunction due to the platelets' inability to store and release certain clotting factors. Symptoms occur mostly in women and may include mild bleeding, nosebleeds, and slightly heavier than normal menstrual periods. People with storage pool disease may also have abnormally low levels of blood platelets (thrombocytopenia).

Some platelet disorders may be associated with congenital conditions such as Wiskott-Aldrich syndrome and thrombocytopenia with absent radius syndrome. For more information on these disorders choose "Wiskott-Aldrich," and "thrombocytopenia with absent radius," as your search terms in the Rare Disease Database.)

Standard Therapies

Diagnosis
Most individuals affected with Glanzmann thrombasthenia have a normal number of platelets but have a prolonged bleeding time, which means it takes longer than usual for a standardized cut to stop bleeding. Platelet aggregation studies are abnormal and show that platelets are not able to clump together when stimulated as they should to form platelet aggregates. Glanzmann thrombasthenia is definitively diagnosed by tests that determine if there is a deficiency of the alpha-IIb or ß3 (GPIIb or GPIIIa) proteins. These tests use techniques involving monoclonal antibodies and flow cytometry. Genetic tests can identify the DNA mutations responsible for the disorder.

Carrier and prenatal testing by DNA analysis is possible if the specific gene abnormality has been identified in an affected family member.

Treatment
Some individuals with GT may require blood platelet transfusions. Since transfusions may continue to be necessary throughout life, affected individuals may benefit from transfusions from an unaffected sibling or an HLA matched donor.

Platelet transfusions should either be given prior to most surgical procedures or should be available if needed. Platelet transfusions are sometimes necessary prior to delivery.

Nosebleeds can be treated with nasal packing or application of foam soaked in thrombin. Regular dental care is important to prevent bleeding from the gums.

Hormonal therapy can be used to suppress menstrual periods.

Other treatment of Glanzmann thrombasthenia is symptomatic and supportive.

Genetic counseling may be of benefit for people with Glanzmann thrombasthenia and their families.

Investigational Therapies

Treatment with desmopressin and recombinant factor VIIa have been effective in some patients. Factor VIIa must be used with caution because of the risk of blood clots. Bone marrow transplantation has successfully cured a few patients with severe disease.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

Glanzmann Thrombasthenia Resources

Organizations:

References

TEXTBOOKS
Coller BS, French DL, and Rao AK. Hereditary qualitative platelet disorders. In: Kaushansky K, Beutler E, Lichtman MA, et al, eds. Williams hematology, 8th ed. New York: McGraw-Hill; 2010:1933-1970.

Mitchell WB and French DL. Glanzmann Thrombasthenia. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins; 2003:383-384.

JOURNAL ARTICLES
Nurden AT, Fiore M, Nurden P, et al. Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 2011;118:5996-6005.

Wiegering V, Winkler B, Langhammer F, et al. Allogeneic hematopoietic stem cell transplantation in Glanzmann thrombasthenia complicated by platelet alloimmunization. Klin Padiatr. 2011;223:173-175.

Kitko CL, Levine JE, Matthews DC, et al. Successful unrelated donor cord blood transplantation for Glanzmann's thrombasthenia. 2011;15:e42-46.

Miller W, Dunn A, Chiang KY. Sustained engraftment and resolution of bleeding phenotype after unrelated cord blood hematopoietic stem cell transplantation for severe glanzmann thrombasthenia. J Pediatr Hematol Oncol. 2009;31:437-439.

Ishaqi MK, El-Hayek M, Gassas A, et al. Allogeneic stem cell transplantation for Glanzmann thrombasthenia. Pediatr Blood Cancer. 2009;52:682-683.

Di Minno G, Coppola A, Di Minno MN, et al. Glanzmann's thrombasthenia (defective platelet integrin alphaIIb-beta3): proposals for management between evidence and open issues. Thromb Haemostas. 2009;102:1157-1164.

Connor P, Khair K, Liesner R, et al. Stem cell transplantation for children with Glanzmann thrombasthenia. Br J Hematol 2008;140:568-571.

Bellucci s, Damaj G, Boval B, et al. Bone marrow transplantation in severe Glanzmann's thrombasthenia with antiplatelet alloimmunization. Bone Marrow Transplant 2000;25:327-330.

French DL, Coller BS. Hematologically important mutations: Glanzmann thrombasthenia. Blood Cells Mol Dis. 1997;23:39-51.

George JN, Caen JP, Nurden AT. Glanzmann thrombasthenis:the spectrum of clinical disease. Blood 1990;75:1383-1395.

INTERNET
Ali ZA. Glanzmann Thrombasthenia. Emedicine. http://emedicine.medscape.com/article/200311-overview. Updated November 22, 2011. Accessed March 2, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Glanzmann Thrombasthenia; GT. Entry No: 273800. Last Edited September 23, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed March 2, 2012.

Nurden AT. Glanzmann Thrombasthenia. From: Orphanet Encyclopedia. http://www.orpha.net/data/patho/GB/uk-Glanzmann.pdf. Updated September 2005. Accessed March 2, 2012.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2012/03/05 00:00:00 GMT+0

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