Functional Domains on Human Platelet Glycoprotein IIb/IIIa.

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Immunological studies by crossed-immi-inoelectrophoresis of the platelets from 22 Japanese thrombasthenic patients (7 males, 13 females) identified 8 cases of type I with no detectable GPIIb/IIIa complex(Integrin alpha_<IIb> beta_3), 9 cases of type II with a trace amount of GPIIb/IIIa and 3 cases of variant type with normal amount of GPIIb/IIIa. Analysis of PCR-amplified CDNA of GPIIIa from the platelets of a thrombasthenic type II patient revealed mutations of 192-193 amino acid residues from His-Val to Gln-Asn. The mutation of GPIIIa may result in poor complex-formation with GPIIb followed by the decrease in the GPIIb/IIIa complex.Determination of intra-platelet fibrinogen in the thrombasthenic platelets showed 4.6 <plus-minus> 1.7% of normals, 21.9<plus-minus> 6.1% and 70.6% in type I (4 cases), type II (7 cases) and variant type (1 case) platelets, respectively. There was a positive correlationship between intra platelet fibrinogen and the residual GPIIb/IIIa in the thrombasthenic platelets, suggesting that membrane GPIIb/IIIa on the circulating non-activated platelets may uptake plasma fibrinogen. The GPIIb/IIIa of the variant type thrombasthenic platelets could not support aggregation induced by ADP because of inability of fibrinogen binding, while they could still uptake plasma fibrinogen as much as normal platelets. This suggests that the fibrinogen binding domain of GPIIb/IIIa is different from a domain uptaking plasma fibrino