A variant of Glanzmann's thrombasthenia characterized by abnormal glycoprotein IIb/IIIa complex formation.
Glanzmann's thrombasthenia is a congenital bleeding abnormality characterized by absent platelet aggregation due to the failure of fibrinogen to bind to activated thrombasthenic platelets. In the majority of cases, this defect is caused by the absence or marked reduction of a specific fibrinogen-binding aggregation receptor, the GP IIb/IIIa complex. E.T., an 18-year-old female with a life-long history of bleeding and easy bruising, had the normal clinical features of Glanzmann's thrombasthenia. Surprisingly, sodium dodecyl sulphate-polyacrylamide gel electrophoresis of her platelets showed no apparent abnormality of the GP IIb/IIIa complex. Control platelets washed in the presence of 2 mM EDTA and control and patient platelets washed in the presence of 2 mM calcium ions showed normal reactivity with anti-GP IIb, anti-GP IIIa, and anti-GP IIb/IIIa complex specific monoclonal antibodies as evaluated by flow cytometry. In contrast, patient's platelets washed in the presence of 2 mM EDTA reacted with anti-GP IIb, anti-GP IIIa, but not with the complex-specific monoclonal antibodies. The increased susceptibility of the patient's GP IIb/IIIa complex to EDTA dissociation was confirmed by crossed immunoelectrophoresis (CIE). CIE analysis further indicated that the patient's GP IIb/IIIa complex did not bind fibrinogen. The combined results suggest that this patient has Glanzmann's thrombasthenia due to an abnormal association of the GP IIb/IIIa complex which results in the failure of the complex to bind fibrinogen.
Fournier
D J
DJ
Department of Medicine, University of Sydney, Westmead Hospital, N.S.W., Australia.
Kabral
A
A
Castaldi
P A
PA
Berndt
M C
MC
D000293:Adolescent; D001791:Blood Platelet Disorders / Q000097:blood*; D002118:Calcium / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008274:Magnesium / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D013915:Thrombasthenia / Q000097:blood*
D010980:Platelet Membrane Glycoproteins; D004492:Edetic Acid; D008274:Magnesium; D002118:Calcium