Inhibition of factor VIIa generation and prothrombin activation by treatment with enoxaparin in patients with unstable angina.
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 < 0.05). 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.
Gerotziafas
Grigoris T
GT
Department of Haematology, Theagenion Cancer Hospital, Thessaloniki, Greece. gerotziafasgrigoris@hotmail.com
Zafiropoulos
Athanasios
A
Van Dreden
Patrick
P
Karavaggeli
Eli
E
Goutzoumas
Nikos
N
Nikolaidis
Paschalis
P
Combot
Caroline
C
Lagoudaki
Pervez
P
Zervas
Kostas
K
Arzoglou
Pantelis
P
Samama
Meyer Michel
MM
D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000097:blood*; D000925:Anticoagulants / Q000494:pharmacology*; D017984:Enoxaparin / Q000494:pharmacology*; D015942:Factor VIIa / Q000187:drug effects* / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin / Q000187:drug effects* / Q000378:metabolism
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D008074:Lipoproteins; D010446:Peptide Fragments; D011498:Protein Precursors; C051928:lipoprotein-associated coagulation inhibitor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D015942:Factor VIIa