History
Initially, patients present with mucocutaneous bleeding in the neonatal period or with bleeding following circumcision.
Children with thrombasthenia may have purpura, epistaxis, gingival bleeding, GI bleeding, and menorrhagia.
The occurrence of most minor bleeding decreases with age.
Severe menorrhagia is a common problem that requires careful observation and treatment with oral contraceptive pills. It is usually associated with an excessively proliferative endometrium that reflects estrogen dominance. [10]
Additional presenting symptoms include GI bleeding and hematuria.
Excessive bleeding following parturition and postsurgical bleeding represent a significant risk.
Although uncommon, hemarthrosis and deep hematomas more characteristic of hemophilias can occur.
Posttraumatic bleeding may be severe in patients not prepared with normal platelets.
Clinical bleeding does not always correlate with the amount of GP IIb-IIIa present.
Interestingly, reports have described thrombosis in patients with congenital thrombocytopenic disorders. Patients with Glanzmann thrombasthenia (GT) have been reported to have venous and arterial thrombosis. [12]
Because the GT trait is recessive, the absence of a family history should not delay a workup for thrombasthenia.
Physical
Most patients with thrombasthenia present with signs of purpura or bleeding.
The initial physical examination should focus on assessing hemodynamic stability.
The diagnosis is made in patients with refractory hemorrhage and appropriate findings on the diagnostic laboratory studies (see Laboratory Studies).
Other than identification of hemorrhage, physical examination findings are of limited use.
Causes
GT is typically inherited as an autosomal recessive disorder. Patients can have homozygous or compound heterozygous mutations in the genes of GPIIb and GPIIIa, leading to quantitative or qualitative abnormalities of the platelet receptor proteins. [13]
Almost 100 different mutations have been identified in GPIIb, which include missense mutations, nonsense mutations, deletions, and insertions, with most being missense mutations. Mutations identified in GPIIIa include missense mutations, nonsense mutations, deletions insertions, inversion/deletions, and rearrangements, with most being missense mutations as well.
About 20% of patients do not have identifiable mutations as a cause of GT. These patients may have mutations in genes involved in transcription of GPIIb and GPIIIa. [14]
Of note, patients with an acquired GT have been reported; they form autoantibodies secondary to lymphoproliferative disorders. [15, 16]
