A case of Glanzmann's thrombasthenia successfully treated with recombinant factor viia during a surgical procedure: observations on the monitoring and the mechanism of action of this drug.

Recombinant factor VIIa (rFVIIa) has been shown to be efficient for the treatment of haemorrhages in patients with Glanzmann's thrombasthenia presenting anti-glycoprotein IIb-IIIa antibodies, but the mechanism of action is not well established and there is no routine laboratory test for the monitoring of rFVIIa. In this study, thrombin generation (TG) test was used to assess the efficacy of rFVIIa ex vivo in a Glanzmann patient with inhibitor, who had a surgery for cholesteatoma. The day before surgery, TG capacity in platelet rich plasma was significantly diminished (Endogenous thrombin potential = 637nM x min) in comparison with the normal control group (1338+/-353 nM x min). Thirty minutes after the first infusion of 90 microg/kg of rFVIIa, TG was increased by 59% (1010 nM x min). rFVIIa was administered as intravenous bolus injection of 90 microg/kg q x 2h during the first 24h, than 66microg/kg q x 2h during 24h and 53 microg/kg q x 2h on the post-operative day 3. Residual TG capacity measured before rFVIIa administration mostly remained above 1000nM x min and the coagulation capacity was not significantly modified after a new injection of rFVIIa. The fibrin network was studied with 3D confocal microscopy using clots obtained with TG test. After rFVIIa infusion, the fibrin network was tighter in comparison with the sample before rFVIIa injection. These results provide further ex vivo evidence on haemostatic efficacy of rFVIIa in Glanzmann's patients.

Inherited bleeding disorder due to familial type 2 platelet cyclo-oxygenase deficiency.

Inherited platelet cyclo-oxygenase (COX) deficiency is a rare bleeding disorder. We report here the first case of familial type 2 platelet COX deficiency responsible for a moderate bleeding phenotype. The propositus was admitted in the emergency department for major epistaxis following treatment with aspirin. Epinephrine closure time is very sensitive to drugs which inhibit COX but the test was normal in patients with inherited COX deficiency. This clinical and biological data suggest that the anti-platelet effect of aspirin may be dependent on mechanisms other than the inhibition of COX. Thrombin generation test confirmed mild bleeding phenotype in patients with COX deficiency as they had normal thrombin generating capacity.

Two novel factor V null mutations associated with activated protein C resistance phenotype/genotype discrepancy.

Activated protein C (APC) resistance phenotype/genotype discrepancy is a very rare event. The objective of this study was to characterize the molecular mechanisms in two cases of APC phenotype/genotype discrepancy. An approach using direct sequencing of each exon and splicing junctions of the factor V gene showed that two novel factor V null mutations combined with heterozygous factor V Leiden mutation were responsible for this discrepancy. Our results suggest the necessity to use both phenotypic and genotypic analyses in some cases to determine an accurate diagnosis.