Glanzmann Thrombasthenia 

  • Author: Zonera Ashraf Ali, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Nov 22, 2011
 

Background

Glanzmann thrombasthenia is a genetic platelet disorder in which the platelet glycoprotein IIb/IIIa (GP IIb/IIIa) complex is either deficient or present but dysfunctional. The genes of both of these proteins are on chromosome 17, and 50% activity of each protein is enough to support normal platelet aggregation. Defects in the GP IIb/IIIa complex leads to defective platelet aggregation and subsequent bleeding.[1, 2, 3, 4, 5, 6, 7]

Glanzmann thrombasthenia is rare and it is inherited in an autosomal recessive pattern. The disorder was first described by Dr. Eduard Glanzmann in 1918.

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Pathophysiology

When an injury occurs, the GP IIb/IIIa receptors play an important role in the adherence of platelets to the endothelium as well as have a role in platelet aggregation.

The GP IIb/IIIa complex binds fibrinogen and/or von Willebrand factor (vWF). Adjacent platelets are cross-linked through GP IIb/IIIa–fibrinogen–GP IIb/IIIa complexes. When the GP IIb/IIIa complex functions abnormally, platelets cannot aggregate. This then leads to increased bleeding.

The GP IIb/IIIa complex is a heterodimer that requires calcium for GP IIb and GP IIIa to associate normally, and both GP IIb and GP IIIa are required for normal platelet function. A defect in either glycoprotein can lead to a bleeding disorder. However, platelet counts do not depend on GP IIb/IIIa, and, therefore, patients with defects in these glycoproteins have normal platelet counts. The morphology of the platelets on a peripheral smear is not unusual.

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Epidemiology

Frequency

International

Glanzmann thrombasthenia is quite rare, is inherited in an autosomal recessive manner, and is observed most often in populations that have increased consanguinity.[8] Reports of families with a high incidence have been observed from countries such as Iran, Israel, and Jordan, where marriage among close relatives is allowed.

Mortality/Morbidity

Bleeding problems can be severe in patients with Glanzmann thrombasthenia, but the prognosis remains good with appropriate supportive care.

Sex

There may a slightly higher female preponderance for Glanzmann thrombasthenia. For a review of pregnancy in women with Glanzmann thrombasthenia, see Siddiq et al.[9]

Age

Patients with thrombasthenia typically present with mucocutaneous bleeding at birth or early in infancy.

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Contributor Information and Disclosures
Author

Zonera Ashraf Ali, MD  Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center

Zonera Ashraf Ali, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Mark J Shumate, MD, MPH  Assistant Professor, Department of Internal Medicine, Division of Hematology/Oncology, Emory University

Mark J Shumate, MD, MPH is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

Wadie F Bahou, MD  Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. George JN, Caen JP, Nurden AT. Glanzmann's thrombasthenia: the spectrum of clinical disease. Blood. Apr 1 1990;75(7):1383-95. [Medline]. [Full Text].

  2. Malik U, Dutcher JP, Oleksowicz L. Acquired Glanzmann's thrombasthenia associated with Hodgkin's lymphoma: a case report and review of the literature. Cancer. May 1 1998;82(9):1764-8. [Medline]. [Full Text].

  3. Nurden AT. Glanzmann thrombasthenia. Orphanet J Rare Dis. Apr 6 2006;1:10. [Medline]. [Full Text].

  4. Poon MC, Zotz R, Di Minno G, et al. Glanzmann's thrombasthenia treatment: a prospective observational registry on the use of recombinant human activated factor VII and other hemostatic agents. Semin Hematol. Jan 2006;43(1 suppl 1):S33-6. [Medline].

  5. Poon MC. Clinical use of recombinant human activated factor VII (rFVIIa) in the prevention and treatment of bleeding episodes in patients with Glanzmann's thrombasthenia. Vasc Health Risk Manag. 2007;3(5):655-64. [Medline]. [Full Text].

  6. Saxena R, Kannan M. Glanzmann's thrombasthenia: an overview. Clin Appl Thromb Hemost. Oct 16 2008;epub ahead of print. [Medline].

  7. van de Vijver E, De Cuyper IM, Gerrits AJ, Verhoeven AJ, Seeger K, Gutiérrez L, et al. Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome: the role of integrin ß1 and ß3 in platelet adhesion to collagen. Blood. Nov 7 2011;[Medline].

  8. Fiore M, Pillois X, Nurden P, Nurden AT, Austerlitz F. Founder effect and estimation of the age of the French Gypsy mutation associated with Glanzmann thrombasthenia in Manouche families. Eur J Hum Genet. Sep 2011;19(9):981-7. [Medline]. [Full Text].

  9. Siddiq S, Clark A, Mumford A. A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia. Haemophilia. Sep 2011;17(5):e858-69. [Medline].

  10. Tholouli E, Hay CR, O'Gorman P, Makris M. Acquired Glanzmann's thrombasthenia without thrombocytopenia: a severe acquired autoimmune bleeding disorder. Br J Haematol. Oct 2004;127(2):209-13. [Medline].

  11. Ali N, Moiz B, Shaikh U, et al. Diagnostic tool for Glanzmann's thrombasthenia clinicopathologic spectrum. J Coll Physicians Surg Pak. Feb 2008;18(2):91-4. [Medline].

  12. Jin PP, Shen WZ, Yang F, et al. [Analysis of clinical features and genotype in three Chinese pedigrees with Glanzmann thrombasthenia]. Zhonghua Xue Ye Xue Za Zhi. Mar 2008;29(3):149-53. [Medline].

  13. Lombardo VT, Sottilotta G. Recombinant activated factor VII combined with desmopressin in preventing bleeding from dental extraction in a patient with Glanzmann's thrombasthenia. Clin Appl Thromb Hemost. Jan 2006;12(1):115-6. [Medline].

  14. Shen WZ, Ding QL, Jin PP, et al. A novel Pro126His beta propeller mutation in integrin alphaIIb causes Glanzmann thrombasthenia by impairing progression of pro-alphaIIbbeta3 from endoplasmic reticulum to Golgi. Blood Cells Mol Dis. Oct 29 2008;epub ahead of print. [Medline].

  15. Vuckovic SA. Glanzmann's thrombasthenia revisited. J Emerg Med. May-Jun 1996;14(3):299-303. [Medline].

 
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