LEVELS OF PROTHROMBIN ACTIVATION PEPTIDE F1+2 IN PATIENTS WITH A BLEEDING TENDENCY

Numerous recent publications point to significant improvements in haem ostasis in the bleeding patient suffering from haemophilia with inhibi tors when a recombinant activated factor VII(rFVIIa) molecule is admin istered in high doses. In theory, activated factor VII (FVIIa) is beli eved to initiate haemostasis through its physiological interaction wit h tissue factor at sites of cellular injury, whereby factor X (FX) act ivation and, in consequence, thrombin formation is amplified. There ha s been speculation, however, whether high circulating FVII procoagulan t (FVII:C) levels may induce systemic coagulation activation. The pres ent retrospective investigation was undertaken to study ex vivo, the i nfluence of treatment with rFVIIa as assessed by the sensitive marker of prothrombin conversion, prothrombin fragment F1+2, in plasma sample s. Study subjects consisted of: seven people suffering from thrombocyt openia participating in a study of the influence of rFVIIa on the blee ding time, in whom serial plasma samples had been collected before and subsequently at 10, 60 and 180 min after infusion of rFVIIa; four hae mophilia A patients with inhibitors to FVIII undergoing surgery; two h aemophilia A patients with inhibitors treated with rFVIIa for minor bl eedings on 16 occasions in whom plasma samples had been collected befo re and 10-15 min after rFVIIa infusion; and two FVII-deficient patient s undergoing treatment with rFVIIa. A group of seven haemophilia A pat ients with no signs of inhibitors subjected to a pharmacokinetic study of a plasma-derived FVIII concentrate served as controls. In the grou p of thrombocytopenic patients our results showed a mean increase in F 1+2 following doses of 50 mu g/kg body weight and 100 mu g/kg body wei ght of rFVIIa of 1.1 and 1.4 nmol/l, respectively, with a gradual incr ease over time, but there was no significant correlation between FVII: C and the corresponding values of F1+2. During and after haemophilic i nhibitor surgery, a mean increase in F1+2 of 1.44 nmol/l (range 0.6-3. 2 nmol/l) was found, whereas 16 matched samples collected during treat ment for minor bleedings showed a mean increase in F1+2 of 0.10 nmol/l (range -0.12 to 0.20 nmol/l). In FVII-deficient individuals, the mean rise in F1+2 was <0.10 nmol/l. In the control group, the mean elevati on of F1+2 was 0.13 nmol/l (range -0.5 to 0.7 nmol/l). Hence, our resu lts show that only discrete changes in F1+2 follow administration of r FVIIa. Blood Coag Fibrinol 9 (suppl 1):S129-S134 (C) 1998 Lippincott-R aven Publishers.