Effects of low molecular weight heparin on a severely antithrombin III-decreased disseminated intravascular coagulation model in rabbits.
The effect of dalteparin, a low molecular weight heparin, on severely antithrombin III (ATIII)-decreased disseminated intravascular coagulation (DIC) model was compared with that of unfractionated heparin (heparin). The DIC model in rabbits was produced by continuous infusion of thrombin in combination with bolus injection of latex. After a 3 hr infusion of thrombin, plasma ATIII activity was lowered to 30% of normal plasma. Platelet number, fibrinogen content and alpha 2 plasmin inhibitor (alpha 2PI) activity were also decreased. Dalteparin (25-100 IU/kg/hr) and heparin (25-100 U/kg/hr) inhibited the decrease in ATIII activity, platelet number and fibrinogen content, and had no effect on alpha 2PI activity. Activated partial thromboplastin time (APTT) was prolonged by heparin (50 and 100 U/kg/hr), but not by dalteparin (25-100 IU/kg/hr). The ratio of anti-factor Xa (F.Xa) activity to anti-thrombin activity for dalteparin (50 IU/kg/hr) was higher than that for heparin (50 U/kg/hr). With the addition of exogenous ATIII, the ratio of anti-F.Xa to anti-thrombin for heparin increased, but that for dalteparin did not change. However, the increased ratio for heparin was still lower than the unchanged ratio for dalteparin. These results suggest that both dalteparin and heparin have the ability to rectify the abnormal parameters of severely ATIII-decreased DIC, and that the effects of dalteparin are mainly involved with anti-F.Xa activity whereas the effects of heparin are via anti-thrombin activity.
Tazawa
S
S
Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Ichikawa
K
K
Misawa
K
K
Fukuyama
J
J
Hamano
S
S
Miyata
H
H
Sakuragawa
N
N
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism*; D017985:Dalteparin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use*; D008297:Male; D010314:Partial Thromboplastin Time; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
D000925:Anticoagulants; D000990:Antithrombin III; D006493:Heparin; D017985:Dalteparin