Effects of a low molecular weight heparin (Fragmin) and of unfractionated heparin on coagulation activation at the site of plug formation in vivo.
The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained directly from a vascular injury site. In a double-blind, randomized, 3-way, cross-over study 18 healthy volunteers were given UFH (150 U/kg s.c.) and 2 doses of LMWH [35 U/kg s.c. (low dose, ld), 75 U/kg s.c. (high dose, hd)]. Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA) were measured in bleeding time blood and in venous blood before and after drug application. In addition, the effects of UFH and LMWH on in vitro coagulation tests were studied. Compared to base line, UFH and both ldLMWH and hdLMWH caused significant reductions of F1+2, TAT and FPA in bleeding time blood at 2 h. A marked effect of UFH and of hdLMWH was also seen at 5 h. The inhibition of FPA generation was more pronounced after hdLMWH compared to ldLMWH. In venous blood, UFH and LMWH caused reductions of F1+2, but not of TAT and FPA. In vitro, UFH predominantly affected the anti-IIa assays (activated partial thromboplastin time, thrombin time) and LMWH mainly the anti-Xa test system. Using a technique that investigates the activated coagulation system in vivo, a time- and dose dependent inhibitory effect of heparin on coagulation activation was detectable.(ABSTRACT TRUNCATED AT 250 WORDS)
Eichinger
S
S
Department of Medicine I, Vienna University Hospital, Austria.
Wolz
M
M
Nieszpaur-Los
M
M
Schneider
B
B
Lechner
K
K
Eichler
H G
HG
Kyrle
P A
PA
D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D017985:Dalteparin / Q000494:pharmacology*; D004311:Double-Blind Method; D065427:Factor Xa Inhibitors; D005344:Fibrinopeptide A / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D011516:Prothrombin / Q000187:drug effects / Q000378:metabolism; D013918:Thrombin Time; D014680:Veins
D015415:Biomarkers; D065427:Factor Xa Inhibitors; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D006493:Heparin; D010447:Peptide Hydrolases; D017985:Dalteparin