Glanzmann Thrombasthenia
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Introduction to Glanzmann Thrombasthenia
Glanzmann thrombasthenia (weak platelets) was described in 1918 by the Swiss pediatrician W.E. Glanzmann as a heterogenous group of bleeding disorders. The hallmark of the disease is the failure of platelets to bind fibrinogen and aggregate in the presence of a variety of physiological agonist such as ADP, thrombin, epinephrine or collagen. Glanzmann thrombasthenia is an autosomal recessive bleeding disorder in which the underlying defect in all patients is an abnormality in the gene encoding either the αIIb or β3 protein of the GPIIb-GPIIIa complex. The GPIIb-GPIIIa complex is a member of integrin family of cell surface receptors and is also called the αIIb-β3 integrin receptor. The platelet GPIIb-GPIIIa complex is the most abundant platelet receptor representing approximately 15% of the total protein on the surface of platelets. Although Glanzmann thrombasthenia is a rare disorder it is the most recognized inherited disorder of platelet function.
Over 200 individuals have been described as having Glanzmann thrombasthenia and in more than 60 cases the molecular defect has been identified. The molecular abnormalities causing Glanzmann thrombasthenia range from major gene deletions and inversions to single point mutations. These mutations have been grouped according to the biochemical consequences and include transcriptional and protein functional defects. Among the functional defects there are protein stability mutants, glycoprotein complex maturation mutants and ligand binding mutants.
Clinical Features of Glanzmann Thrombasthenia
The clinical manifestations of Glanzmann thrombasthenia are significant mucocutaneous bleeding that is evidenced at an early age. Lifelong repeated bleeding at sites of minor trauma such as the gums (gingival) and the nose (epistaxis). In females heavy bleeding during menstruation may require therapeutic intervention. Severe intracranial or gastrointestinal hemorrhage can occur spontaneously (i.e. unprovoked by injury) and is a significant cause of mortality in 5% to 10% of Glanzmann thrombasthenia patients. Treatment of the disorder is limited to local measures such as the application of pressure. Platelet transfusion may be useful but only on a limited basis as resistance will develop to the infused platelets.
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Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu