Subscribe to RSS
DOI: 10.1055/s-0038-1651584
Heparin-Releasable and Platelet Pools of Tissue Factor Pathway Inhibitor in Rabbits
Publication History
Received 12 August 1992
Accepted after revision 26 October 1992
Publication Date:
05 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199303/lookinside/thumbnails/10-1055-s-0038-1651584-1.jpg)
Summary
Earlier studies from this laboratory have established that tissue factor pathway inhibitor (TFPI) functions as a natural anticoagulant protecting rabbits from intravascular coagulation triggered by the exposure of blood to small amounts of tissue factor. In addition to the TFPI circulating in plasma, humans have been shown to have heparin-releasable and platelet pools of TFPI. In order better to extrapolate from studies carried out in rabbits to an understanding of human hemostasis, we have examined the presence and extent of heparin-releasable and platelet pools of TFPI in rabbits. We find that in the rabbit the heparin-releasable pool of TFPI activity, as measured in a capacity assay, may be smaller relative to the plasma pool than in humans; that the platelet pool of TFPI activity is comparable to that of humans; and that rabbit TFPI, unlike human TFPI, has the same apparent molecular mass in all vascular pools. These studies extend our understanding of the properties of TFPI in rabbits and the appropriateness of using the rabbit for studies of TFPI relevant to human hemostasis.
-
References
- 1 Rapaport SI. The extrinsic pathway inhibitor: A regulator of tissue factor-dependent blood coagulation. Thromb Haemostas 1991; 66: 6-15
- 2 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990; 29: 7539-7546
- 3 Sandset PM, Abildgaard U. Extrinsic pathway inhibitor – The key to feedback control of blood coagulation initiated by tissue thromboplastin. Haemostasis 1991; 21: 219-239
- 4 Sandset PM, Warn-Cramer BJ, Rao LVM, Maki SL, Rapaport SI. Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: Evidence supporting a physiologic role for EPI as a natural anticoagulant. Proc Natl Acad Sci USA 1991; 88: 708-712
- 5 Sandset PM, Warn-Cramer BJ, Maki SL, Rapaport SI. Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. Blood 1991; 78: 1496-1502
- 6 Warn-Cramer BJ, Maki SL. Purification of tissue factor pathway inhibitor (TFPI) from rabbit plasma and characterization of its differences from TFPI isolated from human plasma. Thromb Res 1992; 67: 367-383
- 7 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50: 803-813
- 8 Lindahl AK, Abildgaard U, Stokke G. Release of extrinsic pathway inhibitor after heparin injection: Increased response in cancer patients. Thromb Res 1990; 59: 651-656
- 9 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze Jr. GJ. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood 1991; 78: 387-393
- 10 Novotny wF, Girard TJ, Miletich JP, Broze Jr. GJ. Platelets secrete a coagulation inhibitor functionally and antigenically similar to the lipoprotein associated coagulation inhibitor. Blood 1988; 72: 2020-2025
- 11 Rao LVM, Bajaj SP. Purification of human factor VII utilizing O-(diethylaminoethyl-)Sephadex and Sulfopropyl Sephadex chromatography. Anal Biochem 1984; 136: 357-361
- 12 Bajaj SP, Rapaport SI, Prodanos C. A simplified procedure for purification of human prothrombin, factor IX and factor X. Prep Biochem 1981; 11: 397-412
- 13 Rao LVM, Hoang AD. Purification and characterization of rabbit tissue factor. Thromb Res 1989; 56: 109-118
- 14 Rao LVM. Characterization of anti-tissue factor antibody and its use in immunoaffinity purification of human tissue factor. Thromb Res 1988; 51: 373-384
- 15 Mimms LT, Zampighi G, Nozaki Y, Tanford C, Reynolds JA. Phospholipid vesicle formation and transmembrane protein incorporation using octyl glucoside. Biochemistry 1981; 20: 833-840
- 16 Warn-Cramer BJ, Maki SL, Zivelin A, Rapaport SI. Partial purification and characterization of extrinsic pathway inhibitor (the factor Xa-dependent plasma inhibitor of factor VIIa/tissue factor). Thromb Res 1987; 48: 11-22
- 17 Pedersen AH, Nordfang O, Norris F, Wiberg FC, Christensen PM, Moeller KB, Meidahl-Pedersen J, Beck TC, Norris K, Hedner U, Kisiel W. Recombinant human extrinsic pathway inhibitor. J Biol Chem 1990; 265: 16786-16793
- 18 Usharani P, Warn-Cramer BJ, Kasper CK, Bajaj SP. Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. J Clin Invest 1985; 75: 76-83
- 19 Timmons S, Hawiger J. Separation of human platelets from plasma proteins including factor VIIIVWF by a combined albumin gradient-gel filtration method using HEPES buffer. Thromb Res 1978; 12: 297-306
- 20 Handeland GF, Abildgaard U, Aasen AD. Simplified assay for antithrombin III activity using chromogenic peptide substrate. Scand J Haematol 1983; 31: 427-437
- 21 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 1970; 227: 680-685
- 22 Novotny WF, Palmier M, Wun T-C, Broze Jr GJ. Miletich JP Purification and properties of heparin-releasable lipoprotein-associated coagulation inhibitor. Blood 1991; 78: 394-400
- 23 Nordfang O, Bjorn SE, Valentin S, Nielsen LS, Wildgoose P, Beck TC, Hedner U. The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991; 30: 10371-10376
- 24 Wesselschmidt R, Likert K, Girard T, Wun T-C, Broze Jr. GJ. Tissue factor pathway inhibitor: The carboxyl-terminus is required for optimal inhibition of factor Xa. Blood 1992; 79: 2004-2010
- 25 Lindahl AK, Jacobsen PB, Sandset PM, Abildgaard U. Tissue factor pathway inhibitor with high anticoagulant activity is increased in postheparin plasma and in plasma from cancer patients. Blood Coag Fibrinol 1991; 2: 713-721