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.
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.
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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