Involvement of the extrinsic pathway in the activities of low molecular weight heparins.
Anticoagulant effects of the three LMW heparins (LMWHs) Enoxaparine, Fragmin, Logiparin and of unfractionated heparin (UFH) were compared. The heparins were added to plasma to nominal concentration of 0.2 and 0.5 anti XaU/ml plasma. Dilute tissue thromboplastin (TTP) and CaCl2 were added to platelet poor plasma (PPP), platelet rich plasma (PRP) and citrated blood. Thrombin activity was recorded with chromogenic substrate. In PPP, UFH was definitely more inhibitory than LMWH. In PRP, 0.2 U/ml of LMWHs were about as effective as UFH. At 0.5 U/ml PRP, UFH and Logiparin were more effective than Enoxaparine and Fragmin. Factor XII deficient plasma was very sensitive to heparin, and UFH and Logiparin were again more inhibitory. In whole blood, fibrinopeptide A determinations showed that UFH was more inhibitory than LMWH. We conclude that the net anticoagulant effects of these heparins result from interactions with platelets in addition to accelerated inactivation of clotting factors. The in vivo anticoagulant effect of these drugs can therefore not be predicted from their nominal anti Xa and anti IIa effects alone.
Norrheim
L
L
Haematological Research Laboratory, Aker Hospital, Oslo, Norway.
Abildgaard
U
U
Larsen
M L
ML
Lindahl
A K
AK
D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005175:Factor XII Deficiency / Q000097:blood; D065427:Factor Xa Inhibitors; D005344:Fibrinopeptide A / Q000032:analysis; D006493:Heparin / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013925:Thromboplastin / Q000494:pharmacology
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D005344:Fibrinopeptide A; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D013925:Thromboplastin