Glanzmann Thrombasthenia

Glanzmann Thrombasthenia

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Glanzmann Thrombasthenia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • 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

  • None

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.

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.

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.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



NIH/National Heart, Lung and Blood Institute

P.O. Box 30105

Bethesda, MD 20892-0105

Tel: (301)592-8573

Fax: (301)251-1223

Email: nhlbiinfo@rover.nhlbi.nih.gov

Internet: http://www.nhlbi.nih.gov/



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Glanzmann's Research Foundation

3563 Granite Way

Augusta, GA 30907

Tel: (706)533-4818

Email: curegt@comcast.net or helen@curegt.com

Internet: http://www.CureGT.com



Cure Glanzmann's Foundation, Inc.

P.O. Box 741102

Boynton Beach, FL 33474-1102

USA

Tel: (954)529-6642

Email: cureglanzmanns@yahoo.com

Internet: http://www.cureglanzmanns.com



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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