Glanzmann Thrombasthenia

Updated: Mar 18, 2021
  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Overview

Practice Essentials

Glanzmann thrombasthenia (GT) is a rare platelet disorder in which the platelets have qualitative or quantitative deficiencies of the fibrinogen receptor αIIbβ3. [1] Most cases are hereditary, inherited in an autosomal recessive pattern, but acquired GT also occurs. [2] The disorder is named after Dr. Eduard Glanzmann, who first described it in 1918.

Signs and symptoms

Signs and symptoms of GT include the following:

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

See 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 (eg, aspirin and NSAIDs), iron or folate supplementation for anemia, and vaccination for hepatitis B due to the infectious risks associated with multiple transfusions. [3]

Patients with GT who are bleeding require platelet transfusion.

Recombinant coagulation factor VIIa is approved 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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Pathophysiology

The platelet integrin αIIbβ3, also known as the glycoprotein GPIIb/IIIa (CD41/CD61) complex, is essential for normal platelet function. [4] With platelet activation, the αIIbβ3 complex shifts into its active configuration, which allows the binding of fibrinogen and/or von Willebrand factor (vWF). Adjacent platelets are cross-linked through the αIIβ3, resulting in platelet aggregation and hemostasis. When the complex functions abnormally, platelets cannot aggregate, which leads to increased bleeding. [1]

The αIIbβ3 is a heterodimer.The ITGA2B gene codes for the αIIb and the ITGB3 gene codes for the β3. A defect in either glycoprotein can lead to a bleeding disorder. Most patients have a normal platelet size and count. [5] Acquired Glanzmann thrombasthenia is characterized by anti-αIIbβ3 autoantibodies or paraproteins that block platelet aggregation. [6]

 

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Etiology

Hereditary Glanzmann thrombasthenia is caused by autosomal recessive mutations in the ITGA2B or ITGB3 genes, composed of 30 and 15 exons, respectively; they are near-neighbors localizing to chromosome 17q21.31 and 17q21.32. [7]  More than 100 mutations have been reported. [3] The disease is clinically apparent in patients who are homozygous. Glanzmann thrombasthenia is normally of no clinical significance in patients who are heterozygous for this condition. 

Rare acquired forms caused by antibodies against αIIb β3 integrin have been described. Cases have been reported in patients with a variety of underlying disorders, including primary immune thrombocytopenia (ITP); leukemia, lymphoma, solid cancers, and myeloma; other autoimmune diseases; following organ transplantation; during viral and bacterial infections, as well as with the use of certain drugs. [2, 8, 9, 6]

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Epidemiology

Glanzmann thrombasthenia is quite rare; the global prevalence is estimated to be one per million, with higher prevalence rates found in the Middle East, including Iran, Iraq, Saudi Arabia, Jordan, and among both Palestinians and Israelis. Higher rates have also been reported in India and France. [3] Cases are observed most often in populations that have increased consanguinity, consistent with its autosomal recessive inheritance. [10]  

There may a slightly higher female preponderance for Glanzmann thrombasthenia. For a review of pregnancy in women with Glanzmann thrombasthenia, see Siddiq et al. [11]

Patients with thrombasthenia may present with mucocutaneous bleeding at birth or early in infancy, however most patients are diagnosed later in childhood. The risk and prevalence of severe bleeding increases with age. [3]

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Prognosis

Patients with Glanzmann thrombasthenia can have severe bleeding problems, but their prognosis remains good with appropriate supportive care and platelet transfusions if necessary. The bleeding is primarily mucocutaneous in nature. Clinically significant heavy menstrual bleeding is common and can result in repeated hospital admissions and blood transfusions with a resulting adverse effect on quality of life. [12]  

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Patient Education

Educate patients with Glanzmann thrombasthenia that regular dental care is necessary to avoid gingivitis and gingival bleeding. Patients with Glanzmann thrombasthenia should avoid drugs that decrease platelet function or coagulation, such as the following:

  • Aspirin or other NSAIDs

  • Heparin

  • Warfarin

  • Ticlopidine or clopidogrel

  • Glycoprotein IIb/IIIa antagonists, such as abciximab

  • Streptokinase, urokinase, or tissue plasminogen activator (tPA)

  • Volume expanders, such as dextran or hydroxyethyl starch

  • Dipyridamole

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