Heparin requires both antithrombin and extrinsic pathway inhibitor for its anticoagulant effect in human blood.
Heparinization of blood inhibited the generation of fibrinopeptide A (FPA) after addition of thromboplastin (TP). Heparinization was more effective when performed in vivo than in vitro; the amounts of FPA at 60 s incubation were 8% and 32%, respectively, of control values in nonheparinized blood. When monospecific, neutralizing IgG against extrinsic pathway inhibitor (anti-EPI) were added to heparinized blood prior to TP, the amount of FPA increased to 65%. When monospecific IgG blocking antithrombin (anti-AT) was used, the amount of FPA increased to values similar to those in nonheparinized blood. When anti-AT and anti-EPI were both added to heparinized blood, FPA was generated about 25% faster than in normal blood. These results show that EPI contributes significantly to the anticoagulant effect of heparin in human blood.
Abildgaard
U
U
Hematological Research Laboratory, Aker University Hospital, Oslo, Norway.
Lindahl
A K
AK
Sandset
P M
PM
D000911:Antibodies, Monoclonal / Q000276:immunology; D000990:Antithrombin III / Q000378:metabolism*; D001777:Blood Coagulation / Q000187:drug effects*; D005167:Factor VII / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D005344:Fibrinopeptide A / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology / Q000378:metabolism*; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005344:Fibrinopeptide A; D000990:Antithrombin III; D005167:Factor VII; D006493:Heparin; D013925:Thromboplastin