Deficiency of any of the two coagulation in hibitors antithrombin (AT) and tissue factor pathway in hibitor (TFPI) lowers the resistance to thrombosis. He reditary deficiency of AT leads to a high risk of throm bosis, which occasionally responds poorly to heparin therapy. Experimental deficiency of TFPI lowers the re sistance to infusion of both tissue factor and endotoxin, both regarding microvascular thrombosis and fatality. Administration of either AT or TFPI protects against mi cro- and macrovascular thrombosis. Injection of heparin and some other glycosaminoglycans releases intima bound TFPI to the blood. Heparin accelerates the inhib itory effects of both inhibitors, in particular the effect of AT. The influence of the two inhibitors on the various anticoagulant reactions have been studied using blocking antibodies. It is suggested that the anticoagulant and an tithrombotic effects of heparin are mainly mediated by the accelerated inactivation of thrombin, factor IXa and factor X by AT, and augmented inactivation of tissue factor-factor VIIa by TFPI released to the blood.
Bauer KA, Rosenberg RDThe pathophysiology of the pre-thrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood1987;70: 343.
Abildgaard U. , Fagerhol MK, Egeberg O.Comparison of progressive antithrombin activity and the concentrations of three thrombin inhibitors in human plasma. Scand J Clin Lab Invest1970;26:349.
4.
Andersson TR , Sie P., Pelzer H., et al. Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation. Thromb Res1992;66(5):591.
5.
Vinazzer H., Stocker K.Heparin cofactor II: experimental approach to a new assay and clinical results . Thromb Res1991;61:235.
6.
Kisiel W., Canfield WM, Ericsson LH, et al. Anticoagulant properties of bovine plasma protein C following activation by thrombin. Biochemistry1977;16:58324.
7.
Comp PC, Esmon CTRecurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med1984;311:1522.
8.
Svensson PJ, Dahlbäck B.Resistance to activated protein C as a basis for venous thrombosis . N Engl J Med1994;330: 517.
9.
Sanders NL, Bajaj SP, Zivelin A., et al. Inhibition of tissue factor/factor VIIa activity requires factor X and an additional plasma component. Blood1985;66:204.
10.
Rao Lvm, Rapaport SIStudies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood1987;69:645.
11.
Broze GJ, Warren LA, Novotny WF, et al. The lipoprotein-associated coagulation inhibitor that inhibits the factor VIIatissue factor complex also inhibits factor Xa: insight into its possible mechanism of action. Blood1988 ;71:335.
12.
Abildgaard U. , Sandset PM, Lindahl AKTissue factor pathway inhibitor. In: Poller L. Blood coagulation. Edinburgh: Churchill Livingstone, 1993:6.
13.
Hellgren M. , Tengborn L., Abildgaard U.Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and anti-thrombin. Gynecol Obstet Invest1982;14:127.
14.
0degaard OR , Abildgaard U.Antifactor Xa activity in thrombophilia. Studies in a family with AT-III deficiency. Scand J Haematol1977; 18:86.
15.
Johnson EJ, Prentice Crm, Parapia LAPremature arterial disease associated with familial antithrombin III disease . Thromb Haemost1990;63:13.
16.
Boyer C., Wolf M., Vedrenne J., et al. Homozygous variant of antithrombin III: antithrombin Fontainbleau . Thromb Haemost1986;56:18.
17.
Miller N., Hultin MB, Gounder M., et al. Hereditary antithrombin III deficiency; case report and review of recent therapeutic advances. Am J Hematol1986;21:215.
18.
Schulman S. , Tengborn L.Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III. Thromb Haemost1992;68(6):634.
19.
Sandset PM, Warn-Cramer BJ, Rao Lvm, et al. Immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiological role of EPI as a natural anticoagulant . Proc Natl Acad Sci USA1991; 88:708.
20.
Sandset PM, Warn-Cramer BJ, Maki SL, et al. Immunodepletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to the generalized Schwartzman reaction. Blood1991;78: 1496.
21.
Novotny WF, Brown SG, Miletich JP, et al. Plasma antigen levels of lipoprotein associated coagulation inhibitor in patient samples. Blood1991;78:387.
22.
Lindahl AK, Jacobsen Pbj, Sandset PM, et al. Separation of tissue factor pathway inhibitor by heparin affinity: plasma from cancer patients and post-heparin plasma contain increased amounts of a fraction with high anticoagulant activity. Blood Coag Fibrinol1991;2:713.
23.
Mann LT, Jensenius J Chr, Simonsen M, Abildgaard U. Antithrombin III: protection against death after injection of thromboplastin. Science1969;166:517.
24.
Blauhut B., Necek S., Vinazzer H., et al. Substitution therapy with an antithrombin III concentrate in shock and DIC. Thromb Res1982;27:271.
25.
Fourrier F. , Chopin C., Huart J-J., et al. Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest1993;102:882.
26.
Laharrague P., Bierme R., Cerene A., et al. Antithrombin III: substitutive treatment of the hereditary deficiency. Thromb Haemost1980;43:72.
27.
Bick RLAntithrombin therapy in disseminated intravascular coagulation syndromes . Frontiers in Vascular Medicine: An International Symposium. Frankfurt, May 5-8, 1994 .
28.
Girard TJ, Warren LA, Novotny WF, et al. Identification of the 1.4 kb and 4.0 kb messages for the lipoprotein associated coagulation inhibitor and expression of the encoded protein. Thromb Res1989;55:37.
29.
Spokes EG, Wun T-C.Venous thrombosis produced in the vena cava of rabbits by vascular damage and stasis. JMP1992;27:225.
30.
Haskel EJ, Torr SR, Day KC, et al. Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. Circulation1991 ;84: 821.
Lojewski B. , Bacher P., Jeske W., et al. Molecular weight dependence on the release of tissue factor pathway inhibitor after subcutaneous and intravenous actions of heparins. Thromb Haemost1993;69(6):2263.
34.
Bara L., Bloch MF, Choay J., et al. Intravenous injection of pentasaccharide (PS) does not increase TFPI activity in rabbits. Thromb Haemost1993 ;69(6):815.
35.
Lindahl AK, Sandset PM, Abildgaard U.The present status of tissue factor pathway inhibitor. Blood Coag Fibrinol1992; 3(4):439.
36.
Abildgaard U., Lindahl AK, Sandset PMHeparin requires both antithrombin and extrinsic pathway inhibitor for its anticoagulant effect in human blood. Haemostasis1991;21:254.
37.
Lindahl AK, Abildgaard U., Staalesen R.The anticoagulant effect in heparinized blood and plasma resulting from interactions with extrinsic pathway inhibitor. Thromb Res1991; 64:155.
38.
Hamamoto T. , Yamamoto M., Nordfang O., et al. Inhibitory properties of full-length and truncated recombinant tissue factor pathway inhibitor (TFPI) . J Biol Chem1993;268:8704.
39.
Yin ETEffect of heparin on the neutralization of factor Xa and thrombin by the plasma alpha-2-globulin inhibitor. Thromb Haemost1974;33:43.
40.
Kurachi K., Fujikawa K., Schmer G., et al. Inhibition of bovine factor IXa and factor Xa by antithrombin III. Biochemistry1976;15:43.
41.
Huang Z-F.,Wun T-C. ,Broze GJ Jr. Kinetics of factor Xa inhibition by tissue factor pathway inhibitor. J Biol Chem1933;268:26950.
42.
Iversen N., Abildgaard U.Comparison of TFPI and antithrombin as inhibitors of Factor Xa: The effect of heparin. (in press).
43.
Lindhout T. , Willems G., Blezer R., et al. Kinetics of the inhibition of human factor Xa by full-length and truncated tissue factor pathway inhibitor. Biochem J1994;297:131.
44.
Pieters J., Willems G., Hemker HC, Lindhout T.Inhibition of factor IXa and factor Xa by antithrombin III/heparin during factor X activation. J Biol Chem1988 ;263:15313.
