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The in vitro closure time (CT), determined by the Platelet Function Analyzer (PFA-100), is used to monitor patients treated with aspirin. A relatively high percentage of in vitro aspirin resistance was reported despite an adequate inhibition of platelet response to arachidonic acid and we investigated whether high plasma levels of von Willebrand factor ristocetin cofactor activity (vWF:RCo) may contribute to this profile. Platelet aggregation test, CT [collagen adrenaline (CEPI-CT) and collagen adenosine 5'-diphosphate (ADP) (CADP-CT)], and vWF:RCo levels were evaluated in 55 consecutive patients receiving aspirin (75-250 mg/d) versus 32 untreated control subjects. All the aspirin-treated patients showed platelet aggregation responses that reflected the aspirin intake. However, CT data analysis enabled aspirin good-responder (GR) and aspirin bad-responder (BR) patients to be identified. All GR group subjects (n = 27), had a CEPI-CT and a CADP-CT longer than 300 s and 96 s respectively. The BR group (n = 28) had CEPI-CT values below 200 s and all CADP-CT were in the normal range (77 +/- 19 s). Interestingly, the BR plasma vWF:RCo levels were significantly higher (159 +/- 43%) than those of the GR group (121 +/- 34%) (P < 0.01), which were similar to control values (114 +/- 31%). A negative correlation between vWF:RCo and CT values was established. We demonstrate that in vitro aspirin-resistance, revealed by PFA-100 CT prolongation failure, is correlated to increased plasmatic vWF:RCo levels, reinforcing its particular importance in PFA-100 cartridges performance.

Summary. Factor VIIa (FVIIa) and thrombin generation occur in patients suffering an acute coronary event. We studied the effect of treatment with enoxaparin on FVIIa and prothrombin activation in patients with unstable angina. Anti-Xa activity, FVIIa, FVII coagulant activity (FVII:C) and FVII antigen (FVII:Ag), free tissue factor pathway inhibitor (TFPI), and prothrombin fragments 1 + 2 (F1+2) were measured in patients' plasma, over a 24-h treatment period with enoxaparin. All 14 patients recruited in the study (mean age 68 years) were treated with a subcutaneous injection of enoxaparin, 1 mg/kg twice daily. Blood was drawn just before, and at different time intervals after, the first injection. Before enoxaparin administration, the levels of FVIIa (4·02 ± 0·8 ng/ml) and F1+2 (2·68 ± 0·2 nmol/l) were significantly increased as compared with control subjects (2·3 ± 0·3 ng/ml and 0·9 ± 0·1 nmol/l respectively, P

Factor VIIa (FVIIa) and thrombin generation occur in patients suffering an acute coronary event. We studied the effect of treatment with enoxaparin on FVIIa and prothrombin activation in patients with unstable angina. Anti-Xa activity, FVIIa, FVII coagulant activity (FVII:C) and FVII antigen (FVII:Ag), free tissue factor pathway inhibitor (TFPI), and prothrombin fragments 1 + 2 (F1+2) were measured in patients' plasma, over a 24-h treatment period with enoxaparin. All 14 patients recruited in the study (mean age 68 years) were treated with a subcutaneous injection of enoxaparin, 1 mg/kg twice daily. Blood was drawn just before, and at different time intervals after, the first injection. Before enoxaparin administration, the levels of FVIIa (4.02 +/- 0.8 ng/ml) and F1+2 (2.68 +/- 0.2 nmol/l) were significantly increased as compared with control subjects (2.3 +/- 0.3 ng/ml and 0.9 +/- 0.1 nmol/l respectively, P0.05). Free TFPI, FVII:C and FVII:Ag were within normal ranges. One hour after the first injection of enoxaparin, FVIIa and F1+2 levels decreased by 65% and 50%, respectively, and no significant fluctuations were noted throughout the observation period. The concentrations of FVII:C and FVII:Ag were not modified as compared with baseline values. After each injection, the peak concentrations of free TFPI and anti-Xa activity were observed at 2 and 4 h respectively. The kinetics of FVIIa and F1+2 inhibition did not follow those of anti-Xa activity and TFPI release.

Summary. We report the ex vivo effect of recombinant activated factor VII (rFVIIa) on prothrombin activation after whole blood clotting. Two patients with severe thrombocytopenia and life-threatening haemorrhage were successfully managed using a single dose of rFVIIa (90 µg/kg). Western blotting using antiprothrombin antibody showed that rFVIIa did not induce thrombin generation in citrated platelet-poor plasma. Patient sera showed significantly impaired prothrombin activation before and after rFVIIa administration. rFVIIa administration shortened the prothrombin time, activated partial thromboplastin time and Ivy bleeding time, and normalized the clot retraction. These data indicate that rFVIIa accelerated thrombin generation without significant increase of generated thrombin.