A novel amino acid substitution of integrin αIIb in Glanzmann thrombasthenia confirms that the N-terminal region of the receptor plays a role in maintaining ß-propeller structure.

Mutation screening in Glanzmann thrombasthenia (GT) is now advanced. Despite the large number of genetic defects reported in the ITGA2B gene, few affect the structure of the N-terminal domain of the αIIb subunit. We now report a Catalan family where type I GT is given by compound heterozygosity within ITGA2B with a Gly13Val substitution in αIIb associated with a 13 bp deletion involving the splice site of exon 15. Molecular modelling confirmed that the Gly13Val mutation interfered with the structure of the αIIb ß-propeller and confirms that a fold-back of the N-terminus to interact with residues deep within the propeller is necessary for the normal intracellular processing of the maturing αIIbß3 integrin.

Assessment of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects.

BACKGROUND: Aspirin has been routinely prescribed following transcatheter closure of secundum atrial septal defects (ASDs) but its rationale has not been clinically or biologically evaluated; and despite aspirin, thrombotic complications occur following transcatheter ASD closure. We therefore evaluated the presence, degree and timing of the activation of the coagulation and platelet systems following transcatheter closure of ASDs. METHODS AND RESULTS: Fourteen consecutive patients (9 females, mean age 41+/-22 years) who underwent successful transcatheter closure of an ASD defect with the Amplatzer septal occluder were prospectively studied. Measurements of the prothrombin fragment 1+2 (F1+2) levels and the percentage of activated platelets (determined by P-selectin expression detected by flow cytometry) were taken at baseline just before the procedure, and at 1, 7, 30 and 90 days following device implantation. F1+2 levels increased from 0.85+/-0.29 nmol/l at baseline to a maximal value of 1.20+/-0.52 nmol/l at 7 days, gradually returning to the baseline levels at 90 days (0.79+/-0.54 nmol/l) (p<0.001). F1+2 levels at 7 days were also significantly higher than those obtained in a control group of 20 healthy subjects (p=0.016). A greater increase in coagulation activation was observed in cases of residual shunt following ASD closure (r=0.53, p=0.050). No significant variations in the percentage of platelets expressing P-selectin were detected at any time. CONCLUSIONS: Transcatheter closure of ASDs with the Amplatzer septal occluder was associated with a significant increase in F1+2 levels during the first week after device implantation, but there was no detectable effect on platelet system activation. These findings raise the question whether the optimal prophylactic approach following transcatheter ASD closure should be anticoagulant instead of antiplatelet therapy.