Glanzmann’s Thrombasthemia

Overview

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.

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

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.

Symptoms

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

The clinical history of Glanzmann thrombasthenia may include the following:

Excessive bleeding after dental extraction (this may often be the first sign of the disease)

Petechiae and ecchymoses (although spontaneous petechiae are uncommon)

Menorrahgia, often worse at menarche

Gingival bleeding (which is worse with poor dental hygiene)

Epistaxis

Hemarthroses (rare)

Family history of a bleeding disorder may or may not exist

Gastrointestinal bleeding or hematuria is less common

Causes

Glanzmann thrombasthenia is quite rare, is inherited in an autosomal recessive manner, and is observed most often in populations that have increased consanguinity. 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.

Glanzmann thrombasthenia is a genetic condition. 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 GP IIb/IIIa have been described. One such affected patient developed non-Hodgkin lymphoma, and another had no underlying cause.

Prognosis

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