The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients. A randomised controlled trial.
Non-surgical cancer patients are at high thrombotic risk. We hypothesised that the prothrombotic state is reflected by elevated thrombin generation and can be mitigated by increasing the low-molecular-weight heparin (LMWH) dose. Non-surgical cancer patients were randomised to enoxaparin 40 or 80 mg. D-dimer, prothrombin fragment F1+2 (F1+2) and peak thrombin (PT) were measured 2, 4, 6 hours (h) after LMWH (day 1) and daily for 4 days. A total of 22 and 27 patients received enoxaparin 40 and 80 mg, respectively. D-dimer and F1+2 moderately decreased after 6 h in both groups. After enoxaparin 80 mg, D-dimer baseline levels [median (quartiles)] decreased from day 1 to 4 [1054.9 (549.5, 2714.0) vs. 613.0 (441.1, 1793.5) ng/ml] (p<0.0001), while no difference was seen after 40 mg. Baseline PT levels [median (quartiles)] were 426.2 nM (347.3, 542.3) (40 mg) and 394.0 nM (357.1, 448.8) (80 mg). After 80 mg, PT significantly decreased to 112.4 nM (68.5, 202.4), 57.1 nM (38.0, 101.2) and 43.6 nM (23.4, 112.8) after 2, 4 and 6 h, which was lower than after 40 mg (p=0.003). After 80 mg, PT decreased from day 1 to 4 [358.6 nM (194.2, 436.6); p=0.06] while no difference was seen after 40 mg. In conclusion, in cancer patients coagulation activation and thrombin generation is substantially increased. Peak thrombin levels are sensitive to the anticoagulant effects of LMWH at different dosages. The prothrombotic state is substantially attenuated by higher LMWH doses.
Traby
Ludwig
L
Department of Internal Medicine I, Division of Hematology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria. sabine.eichinger@meduniwien.ac.at
Kaider
Alexandra
A
Schmid
Rainer
R
Kranz
Alexander
A
Quehenberger
Peter
P
Kyrle
Paul A
PA
Eichinger
Sabine
S
D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D054796:Drug Dosage Calculations; D017984:Enoxaparin / Q000627:therapeutic use; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D054556:Venous Thromboembolism / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D006495:Heparin, Low-Molecular-Weight; C036309:fibrin fragment D; D011516:Prothrombin; D013917:Thrombin