Glanzmann Thrombasthenia

Updated: Mar 31, 2015
  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Overview

Practice Essentials

Glanzmann thrombasthenia (GT) is a rare genetic platelet disorder in which the platelets have qualitative or quantitative deficiencies of the fibrinogen receptor αIIbβ3.

Signs and symptoms

Signs and symptoms of GT include the following:

  • Mucosal bleeding
  • Gingival bleeding
  • Petechiae and ecchymoses
  • Mennorhagia
  • Gastrointestinal bleeding

See Clinical Presentation for more detail.

Diagnosis

The workup for GT may include complete blood cell count, prothrombin time, and activated partial thromboplastin time. Flow cytometry and monoclonal antibodies confirm the diagnosis.

See Workup for more detail.

Management

Treatment of GT includes preventive measures such as avoidance of antiplatelet agents (e.g., aspirin and NSAIDs), iron or folate supplementation for anemia, and vaccination for hepatitis B due to the infectious risks associated with multiple transfusions.

Patients with GT who are bleeding require platelet transfusion.

Recombinant coagulation factor VIIa was approved by the FDA in July 2014 for bleeding episodes and perioperative management in patients with GT refractory to platelet transfusions, with or without antibodies to platelets.

See Treatment and Medication for more detail.

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Background

Glanzmann thrombasthenia is a genetic platelet disorder in which the platelet have qualitative or quantitative deficiencies of the fibrinogen receptor αIIbβ3. 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 αIIbβ3 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 αIIbβ3 receptors play an important role in the adherence of platelets to the endothelium as well as have a role in platelet aggregation.

The αIIbβ3 complex binds fibrinogen and/or von Willebrand factor (vWF). Adjacent platelets are cross-linked through the αIIβ3. When the complex functions abnormally, platelets cannot aggregate. This then leads to increased bleeding.

The αIIbβ3 is a heterodimer that requires calcium for it to associate normally.The ITGA2B and ITGB3 code the αIIbβ3 integrin. Both genes are needed for the normal platelet function. The ITGA2B gene code for the αIIb and the ITGB3 codes for the β3. A defect in either glycoprotein can lead to a bleeding disorder. The majority of the patients have a normal platelet size and count. [8]

International

Glanzmann thrombasthenia is quite rare, is inherited in an autosomal recessive manner, and is observed most often in populations that have increased consanguinity. [9] Reports of families with a high incidence have been observed from countries such as Iran, Israel, and Jordan, where marriage among close relatives is not uncommon.

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Mortality/Morbidity

Bleeding problems can be severe in patients with Glanzmann thrombasthenia, but the prognosis remains good with appropriate supportive care. The bleeding is primarily mucocutaneous in nature. Generally, bleeding incidence decreases with age.

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. [10]

Age

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

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