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Last updated: 5/24/2023
Years published: 1986, 1990, 1994, 2004, 2007, 2009, 2012, 2015, 2018, 2023
NORD gratefully acknowledges 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.
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.
The symptoms of Glanzmann thrombasthenia usually begin at birth or shortly thereafter and include the tendency to bruise and 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 small or large red or purple-colored spots on the skin that are caused by bleeding in the skin (purpura). Women with GT often also have unusually heavy menstrual bleeding, irregular uterine bleeding and excess bleeding in childbirth. Rarely, gastrointestinal 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.
Glanzmann thrombasthenia is inherited in an autosomal recessive pattern. An abnormality in either the gene for aIIb (glycoprotein IIb; GPIIb) or the gene for ฮฒ3 (glycoprotein IIIa; GPIIIa) results in an abnormal platelet aIIbฮฒ3 (GPIIb/IIIa) integrin family receptor and prevents platelets from forming a plug when bleeding occurs. Many different changes (mutations or variants) in these genes have been identified. Recent evidence suggests that approximately 0.5% of healthy individuals in the general population are probably carrying one gene with an abnormal (pathogenic) variant of ฮฑIIb or ฮฒ3.
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 an abnormal variant of a gene from each parent. If an individual receives one normal gene and one abnormal variant 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 abnormal gene variant 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 is 25%. The risk is the same for males and females.
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 500 cases have been reported, but many cases have probably not 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.
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 ฮฑIIbฮฒ3 (GPIIb/IIIa) receptor. These tests usually involve monoclonal antibodies and flow cytometry. Genetic tests can identify the abnormal gene variants responsible for the disorder in the genes ITGA2B and ITGB3.
Carrier and prenatal testing by DNA analysis is possible if the specific gene variants been identified in an affected family member. Otherwise, prenatal testing can be performed based on analyzing platelet ฮฑIIbฮฒ3 in the fetus.
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 HLA-matched donors. Some patients develop antibodies to transfused platelets and these antibodies may diminish the benefit from subsequent platelet transfusions.
In 2014, NovoSeven RT, a recombinant factor VIIa product, was approved to treat Glanzmann thrombasthenia. This medication is indicated to treat bleeding episodes and perioperative management when platelet transfusions are not effective. Treatment is usually given prior to most surgical procedures or should be available if needed. Platelet transfusions are usually necessary prior to delivery.
Nosebleeds can usually 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 GT is included use of antifibrinolytic agents alone or in combination with other therapies.
Genetic counseling is recommended for people with GT and their families.
Bone marrow or peripheral blood hematopoietic stem cell transplantation has successfully cured several 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: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Rao, A.K., Coller, B.S. Hereditary qualitative platelet disorders. In Williams Hematology, 9th Edition, Kaushansky, K., Lichtman, M.A., Prchal, J.T., Levi, M.M., Press, O.W., Burns, L.J., Caligiuri, M.A., eds. McGraw-Hill, Inc., New York, 2015, pps 2039-2071.
Mitchell WB and French DL. Glanzmann Thrombasthenia. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins; 2003:383-384.
JOURNAL ARTICLES
Li JH, Sun SW, Ai Y, Yang X, Zhu Y P. Excellent outcome following sibling peripheral blood hematopoietic stem cell transplantation for Glanzmann thrombasthenia: A case report. Front. Pediatr. February 7, 2022.
Nurden AT, Pillois X. ITGA2B and ITGB3 gene mutations associated with Glanzmann thrombasthenia. Platelets. 2018;29:98-101.
Poon M-C, Di Minno G, dโOiron R, Zotz R. New insights into the treatment of Glanzmann thrombasthenia. Transfus Med Rev. 2016;30: 92-99.
Buitrago, L., Rendon, A., Liang, Y., Turro, E., Simeoni, I., Negri, A., ThromboGenomics Consortium, Filizola, M., Ouwehand, W.H., Coller. B.S. ฮฑIIbฮฒ3 variants defined by next generation sequencing: predicting variants likely to cause Glanzmann thrombasthenia. PNAS. 2015;112:E1898-19907.
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 Glanzmannโs 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. Glanzmannโs 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 Glanzmannโs 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. Medscape. March 18, 2021. https://emedicine.medscape.com/article/200311-overview Accessed Dec 15, 2022.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Glanzmann Thrombasthenia; GT. Entry No: 273800. Last Edited 02/09/2022. Available at: https://omim.org/entry/273800 Accessed Dec 15, 2022.
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Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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