Inhibition of factor VIIa generation and prothrombin activation by treatment with enoxaparin in patients with unstable angina*

Abstract

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 (F 1+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 (4AE02 ± 0AE8 ng/ml) and F 1+2 (2AE68 ± 0AE2 nmol/l) were significantly increased as compared with control subjects (2AE3 ± 0AE3 ng/ml and 0AE9 ± 0AE1 nmol/l respectively, P < 0AE05). Free TFPI, FVII:C and FVII:Ag were within normal ranges. One hour after the first injection of enoxaparin, FVIIa and F 1+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 F 1+2 inhibition did not follow those of anti-Xa activity and TFPI release.

Effect of gamma irradiation with 30 Gy on the coagulation system in leukoreduced fresh‐frozen plasma

“…Because both groups used the same assay to measure F1+2 as we did, we have no explanation for this difference 27,28 . In contrast, compared to other studies with the same assay, F1+2 levels we found are only slightly above those described in healthy controls 29 and considerably lower than F1+2 levels found in patients undergoing coronary artery bypass grafting during surgery 30 …”

Influence of prolonged dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease

“…LMW heparins furthermore inhibit the initiation of coagulation by mobilization of tissue factor pathway inhibitor from endothelial cells [24]. Short-term treatment with LMW heparins in unstable CAD has previously been shown to reduce coagulation activity with decreased levels of activated factor VII, prothrombin fragment 1 + 2 and D-dimer [14][15][16][17]. In concordance, the prolonged dalteparin treatment in the present study resulted in marked reduction of coagulation activity with significantly lower levels of all three coagulation markers, factor VIIa, prothrombin fragment 1 + 2 and D-dimer, up to 3 months after the acute phase.…”

Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment

“…Although data specific to STEMI are lacking, the pharmacokinetic profile of subcutaneous enoxaparin appears to be similar in healthy individuals and those with unstable angina, with appropriate anticoagulation levels generally achieved 45 min to 60 min following administration (antifactor Xa greater than 0.5 U/mL) (15,16). The interval from enoxaparin administration until first balloon inflation exceeded these values in our index cases.…”