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Heparin Cofactor II

  • Chapter
Chemistry and Biology of Serpins

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 425))

Abstract

Heparin cofactor II (HCII) is a serpin that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin. Both of these glycosaminoglycans bind to HCII and increase the rate of inhibition of thrombin >1000-fold. This review will focus on the biochemistry of HCII and the mechanism by which glycosaminoglycans stimulate its activity.

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References

  1. Tollefsen, D.M., Majerus, D.W. and Blank, M.K. (1982) Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J. Biol. Chem. 257: 2162–2169.

    PubMed  CAS  Google Scholar 

  2. Ragg, H. (1986) A new member of the plasma protease inhibitor gene family. Nucleic Acids Res. 14: 1073–1088.

    Article  PubMed  CAS  Google Scholar 

  3. Blinder, M.A., Marasa, J.C., Reynolds, C.H., Deaven, L.L. and Tollefsen, D.M. (1988) Heparin cofactor II: cDNA sequence, chromosome localization, restriction fragment length polymorphism, and expression in Escherichia coli. Biochemistry 27: 752–759.

    Article  PubMed  CAS  Google Scholar 

  4. Hortin, G., Tollefsen, D.M. and Strauss, A.W. (1986) Identification of two sites of sulfation of human heparin cofactor II. J. Biol. Chem. 261: 15827–15830.

    PubMed  CAS  Google Scholar 

  5. Church, F.C., Pratt, C.W. and Hoffman, M. (1991) Leukocyte chemoattractant peptides from the serpin heparin cofactor II. J. Biol. Chem. 266: 704–709.

    PubMed  CAS  Google Scholar 

  6. Kim, Y.-S., Lee, K.-B. and Linhardt, R.J. (1988) Microheterogeneity of plasma glycoproteins heparin cofactor II and antithrombin III and their carbohydrate analysis. Thromb. Res. 51: 97–104.

    CAS  Google Scholar 

  7. Church, F.C., Meade, J.B. and Pratt, C.W. (1987) Structure-function relationships in heparin cofactor II: spectral analysis of aromatic residues and absence of a role for sulfhydryl groups in thrombin inhibition. Arch. Biochem. Biophys. 259: 331–340.

    CAS  Google Scholar 

  8. Griffith, M.J., Noyes, C.M., Tyndall, J.A. and Church, F.C. (1985) Structural evidence for leucine at the reactive site of heparin cofactor II. Biochemistry 24: 6777–6782.

    Article  PubMed  CAS  Google Scholar 

  9. Church, F.C., Noyes, C.M. and Griffith, M.J. (1985) Inhibition of chymotrypsin by heparin cofactor II. Proc. Natl. Acad. Sci. U. S. A. 82: 6431–6434.

    Article  PubMed  CAS  Google Scholar 

  10. Parker, K.A. and Tollefsen, D.M. (1985) The protease specificity of heparin cofactor II. Inhibition of thrombin generated during coagulation. J. Biol. Chem. 260: 3501–3505.

    PubMed  CAS  Google Scholar 

  11. Derechin, V.M., Blinder, M.A. and Tollefsen, D.M. (1990) Substitution of arginine for Leu444 in the reactive site of heparin cofactor II enhances the rate of thrombin inhibition. J. Biol. Chem. 265: 5623–5628.

    PubMed  CAS  Google Scholar 

  12. Herzog, R., Lutz, S., Blin, N., Marasa, J.C., Blinder, M.A. and Tollefsen, D.M. (1991) Complete nucleotide sequence of the gene for human heparin cofactor II and mapping to chromosomal band 22g11. Biochemistry 30: 1350–1357.

    Article  PubMed  CAS  Google Scholar 

  13. Kim, U.-J., Shizuya, H., Kang, H.-L., Choi, S.-S., Garrett, C.L., Smink, L.J., Birren, B.W., Korenberg, J.R., Dunham, I. and Simon, M.I. (1996) A bacterial artificial chromosome-based framework contig map of human chromosome 22q. Proc. Natl. Acad. Sci. U. S. A. 93: 6297–6301.

    Article  PubMed  CAS  Google Scholar 

  14. Ragg, H. and Preibisch, G. (1988) Structure and expression of the gene coding for the human serpin hLS2. J. Biol. Chem. 263: 12129–12134.

    PubMed  CAS  Google Scholar 

  15. Zhang, G.S., Mehringer, J.H., Van Deerlin, V.M., Kozak, C.A. and Tollefsen, D.M. (1994) Murine heparin cofactor II: purification, eDNA sequence, expression, and gene structure. Biochemistry 33: 3632–3642.

    Article  PubMed  CAS  Google Scholar 

  16. Jaffe, E.A., Armellino, D. and Tollefsen, D.M. (1985) Biosynthesis of functionally active heparin cofactor II by a human hepatoma-derived cell line. Biochem. Biophys. Res. Commun. 132: 368–374.

    CAS  Google Scholar 

  17. Tollefsen, D.M. and Pestka, C.A. (1985) Heparin cofactor II activity in patients with disseminated intravascular coagulation and hepatic failure. Blood 66: 769–774.

    PubMed  CAS  Google Scholar 

  18. Sié, P., Dupouy, D., Pichon, J. and Boneu, B. (1985) Turnover study of heparin cofactor II in healthy man. Thromb. Haemost. 54: 635–638.

    Google Scholar 

  19. Pratt, C.W., Church, F.C. and Pizzo, S.V. (1988) In vivo catabolism of heparin cofactor II and its complex with thrombin: evidence for a common receptor-mediated clearance pathway for three serine proteinase inhibitors. Arch. Biochem. Biophys. 262: 111–117.

    Article  PubMed  CAS  Google Scholar 

  20. Kounnas, M.Z., Church, F.C., Argraves, W.S. and Strickland, D.K. (1996) Cellular internalization and degradation of antithrombin III-thrombin, heparin cofactor II-thrombin, and al-antitrypsin-trypsin complexes is mediated by the low density lipoprotein receptor-related protein. J. Biol. Chem. 271: 6523–6529.

    Article  PubMed  CAS  Google Scholar 

  21. Bertina, R.M., van der Linden, I.K., Engesser, L., Muller, H.P. and Brommer, E.J.P. (1987) Hereditary heparin cofactor II deficiency and the risk of development of thrombosis. Thromb. Haemost. 57: 196–200.

    CAS  Google Scholar 

  22. Ezenagu, L.C. and Brandt, J.T. (1986) Laboratory determination of heparin cofactor II. Arch. Pathol. Lab. Med. 110: 1149–1151.

    PubMed  CAS  Google Scholar 

  23. Andrew, M., Paes, B., Milner, R., Johnston, M., Mitchell, L., Tollefsen, D.M. and Powers, P. (1987) Development of the human coagulation system in the full-term infant. Blood 70: 165–172.

    PubMed  CAS  Google Scholar 

  24. Sandset, P.M. and Andersson, T.R. (1989) Coagulation inhibitor levels in pneumonia and stroke: changes due to consumption and acute phase reaction. J. Intern. Med. 225: 311–316.

    Article  PubMed  CAS  Google Scholar 

  25. Koike, C., Hayakawa, Y., Niiya, K., Sakuragawa, N. and Sasaki, H. (1996) The production of heparin cofactor II is not regulated by inflammatory cytokines in human hepatoma cells: comparison with plasminogen activator inhibitor type-1. Thromb. Haemost. 75: 298–302.

    CAS  Google Scholar 

  26. Westrup, D. and Ragg, H. (1994) Secondary thrombin-binding site, glycosaminoglycan binding domain and reactive center region of leuserpin-2 are strongly conserved in mammalian species. Biochim. Biophys. Acta 1217: 93–96.

    Article  PubMed  CAS  Google Scholar 

  27. Sheffield, W.P., Schuyler, P.D. and Blajchman, M.A. (1994) Molecular cloning and expression of rabbit heparin cofactor 11: a plasma thrombin inhibitor highly conserved between species. Thromb. Haemost. 71: 778–782.

    CAS  Google Scholar 

  28. Borriello, F. and Krauter, K.S. (1991) Multiple murine al-protease inhibitor genes show unusual evolutionary divergence. Proc. Natl. Acad. Sci. U. S. A. 88: 9417–9421.

    Article  PubMed  CAS  Google Scholar 

  29. Inglis, J.D. and Hill, R.E. (1991) The murine Spi-2 proteinase inhibitor locus: a multigene family with a hypervariable reactive site domain. EMBO J. 10: 255–261.

    PubMed  CAS  Google Scholar 

  30. Tollefsen, D.M., Pestka, C.A. and Monafo, W.J. (1983) Activation of heparin cofactor II by dermatan sulfate. J. Biol. Chem. 258: 6713–6716.

    PubMed  CAS  Google Scholar 

  31. Pratt, C.W., Whinna, H.C., Meade, J.B., Treanor, R.E. and Church, F.C. (1989) Physicochemical aspects of heparin cofactor II. Ann. N. Y. Acad. Sci. 556: 104–115.

    Article  PubMed  CAS  Google Scholar 

  32. Klauser, R.J. (1991) Interaction of the sulfated lactobionic acid amide LW 10082 with thrombin and its endogenous inhibitors. Thromb. Res. 62: 557–565.

    CAS  Google Scholar 

  33. Hayakawa, Y., Hayashi, T., Hayashi, T., Niiya, K. and Sakuragawa, N. (1995) Selective activation of heparin cofactor II by a sulfated polysaccharide isolated from the leaves of Artemisia princeps. Blood Coagul. Fibrinolysis 6: 643–649.

    CAS  Google Scholar 

  34. Nagase, H., Enjyoji, K., Minamiguchi, K., Kitazato, K.T., Kitazato, K., Saito, H. and Kato, H. (1995) Depolymerized holothurian glycosaminoglycan with novel anticoagulant actions: antithrombin III- and heparin cofactor II-independent inhibition of factor X activation by factor IXa-factor VIIIa complex and heparin cofactor II-dependent inhibition of thrombin. Blood 85: 1527–1534.

    PubMed  CAS  Google Scholar 

  35. Melton, L.G., Church, F.C. and Erickson, B.W. (1995) Designed polyanionic coiled-coil proteins: acceleration of heparin cofactor II inhibition of thrombin. Int. J. Pept. Protein Res. 45: 44–52.

    Article  PubMed  CAS  Google Scholar 

  36. Bourin, M.-C. and Lindahl, U. (1993) Glycosaminoglycans and the regulation of blood coagulation. Biochem. J. 289: 313–330.

    PubMed  CAS  Google Scholar 

  37. Maimone, M.M. (1990) Characterization of heparin and dermatan sulfate molecules that bind and activate heparin cofactor II. Ph. D. thesis. Washington University, St. Louis.

    Google Scholar 

  38. Maimone, M.M. and Tollefsen, D.M. (1988) Activation of heparin cofactor II by heparin oligosaccharides. Biochem. Biophys. Res. Commun. 152: 1056–1061.

    CAS  Google Scholar 

  39. Sié, P., Petitou, M., Lormeau, J.-C., Dupouy, D., Boneu, B. and Choay, J. (1988) Studies on the structural requirements of heparin for the catalysis of thrombin inhibition by heparin cofactor II. Biochim. Biophys. Acta 966: 188–195.

    Google Scholar 

  40. Bray, B., Lane, D.A., Freyssinet, J.-M., Pejler, G. and Lindahl, U. (1989) Anti-thrombin activities of heparin. Effect of saccharide chain length on thrombin inhibition by heparin cofactor II and by antithrombin. Biochem. J. 262: 225–232.

    CAS  Google Scholar 

  41. Conrad, H.E. (1989) Structure of heparan sulfate and dermatan sulfate. Ann. N. Y. Acad. Sci. 556: 18–28.

    Article  PubMed  CAS  Google Scholar 

  42. Maimone, M.M. and Tollefsen, D.M. (1990) Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. J. Biol. Chem. 265: 18263–18271.

    PubMed  CAS  Google Scholar 

  43. Mascellani, G., Liverani, L., Prete, A., Guppola, P.A., Bergonzini, G. and Bianchini, P. (1994) Relative influence of different disulphate disaccharide clusters on the HCII-mediated inhibition of thrombin by dermatan sulphates of different origins. Thromb. Res. 74: 605–615.

    CAS  Google Scholar 

  44. Pavâo, M.S.G., Mourâo, P.A.S., Mulloy, B. and Tollefsen, D.M. (1995) A unique dermatan sulfate-like glycosaminoglycan from ascidian. Its structure and the effect of its unusual sulfation pattern on anticoagulant activity. J. Biol. Chem. 270: 31027–31036.

    Article  PubMed  Google Scholar 

  45. Andersson, T.R., Larsen, M.L. and Abildgaard, U. (1987) Low heparin cofactor II associated with abnormal crossed immunoelectrophoresis pattern in two Norwegian families. Thromb. Res. 47: 243–248.

    CAS  Google Scholar 

  46. Blinder, M.A., Andersson, T.R., Abildgaard, U. and Tollefsen, D.M. (1989) Heparin cofactor II Oslo. Mutation of Arg-189 to His decreases the affinity for dermatan sulfate. J. Biol. Chem. 264: 5128–5133.

    PubMed  CAS  Google Scholar 

  47. Blinder, M.A. and Tollefsen, D.M. (1990) Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. J. Biol. Chem. 265: 286–291.

    PubMed  CAS  Google Scholar 

  48. Ragg, H., Ulshöfer, T. and Gerewitz, J. (1990) On the activation of human leuserpin-2, a thrombin inhibitor, by glycosaminoglycans. J. Biol. Chem. 265: 5211–5218.

    PubMed  CAS  Google Scholar 

  49. Ragg, H., Ulshöfer, T. and Gerewitz, J. (1990) Glycosaminoglycan-mediated leuserpin-2/thrombin interaction. Structure-function relationships. J. Biol. Chem. 265: 22386–22391.

    PubMed  CAS  Google Scholar 

  50. Whinna, H.C., Blinder, M.A., Szewczyk, M., Tollefsen, D.M. and Church, F.C. (1991) Role of lysine 173 in heparin binding to heparin cofactor II. J. Biol. Chem. 266: 8129–8135.

    PubMed  CAS  Google Scholar 

  51. Rydel, T.J., Ravichandran, K.G., Tulinsky, A., Bode, W., Huber, R., Roitsch, C. and Fenton, J.W., II (1990) The structure of a complex of recombinant hirudin and human a-thrombin. Science 249: 277–280.

    Article  PubMed  CAS  Google Scholar 

  52. Hortin, G.L., Tollefsen, D.M. and Benutto, B.M. (1989) Antithrombin activity of a peptide corresponding to residues 54–75 of heparin cofactor II. J. Biol. Chem. 264: 13979–13982.

    PubMed  CAS  Google Scholar 

  53. Van Deerlin, V.M.D. and Tollefsen, D.M. (1991) The N-terminal acidic domain of heparin cofactor II mediates the inhibition of a-thrombin in the presence of glycosaminoglycans. J. Biol. Chem. 266: 20223–20231.

    PubMed  Google Scholar 

  54. Sheffield, W.P. and Blajchman, M.A. (1995) Deletion mutagenesis of heparin cofactor II: defining the minimum size of a thrombin inhibiting serpin. FEBS Lett. 365: 189–192.

    Article  PubMed  CAS  Google Scholar 

  55. Rogers, S.J., Pratt, C.W., Whinna, H.C. and Church, F.C. (1992) Role of thrombin exosites in inhibition by heparin cofactor Il. J. Biol. Chem. 267: 3613–3617.

    PubMed  CAS  Google Scholar 

  56. Phillips, J.E., Shirk, R.A., Whinna, H.C., Henriksen, R.A. and Church, F.C. (1993) Inhibition of dysthrombins Quick I and II by heparin cofactor II and antithrombin. J. Biol. Chem. 268: 3321–3327.

    PubMed  CAS  Google Scholar 

  57. Sheehan, J.P., Wu, Q., Tollefsen, D.M. and Sadler, J.E. (1993) Mutagenesis of thrombin selectively modulates inhibition by serpins heparin cofactor II and antithrombin III. Interaction with the anion-binding exosite determines heparin cofactor II specificity. J. Biol. Chem. 268: 3639–3645.

    PubMed  CAS  Google Scholar 

  58. Griffith, M.J. (1983) Heparin-catalyzed inhibitor/protease reactions: kinetic evidence for a common mechanism of action of heparin. Proc. Natl. Acad. Sci. U. S. A. 80: 5460–5464.

    Article  PubMed  CAS  Google Scholar 

  59. Tollefsen, D.M., Peacock, M.E. and Monafo, W.J. (1986) Molecular size of dermatan sulfate oligosaccharides required to bind and activate heparin cofactor II. J. Biol. Chem. 261: 8854–8858.

    PubMed  CAS  Google Scholar 

  60. Sheehan, J.P., Tollefsen, D.M. and Sadler, J.E. (1994) Heparin cofactor II is regulated allosterically and not primarily by template effects. Studies with mutant thrombins and glycosaminoglycans. J. Biol. Chem. 269: 32747–32751.

    PubMed  CAS  Google Scholar 

  61. Sheehan, J.P. and Sadler, J.E. (1994) Molecular mapping of the heparin-binding exosite of thrombin. Proc. Natl. Acad. Sci. U. S. A. 91: 5518–5522.

    Article  PubMed  CAS  Google Scholar 

  62. Teien, A.N., Abildgaard, U. and Höök, M. (1976) The anticoagulant effect of heparan sulfate and dermatan sulfate. Thromb. Res. 8: 859–863.

    CAS  Google Scholar 

  63. Tollefsen, D.M. and Blank, M.K. (1981) Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J. Clin. Invest. 68: 589–596.

    Article  PubMed  CAS  Google Scholar 

  64. Sié, P., Ofosu, F., Fernandez, F., Buchanan, M.R., Petitou, M. and Boneu, B. (1986) Respective role of antithrombin III and heparin cofactor II in the in vitro anticoagulant effect of heparin and of various sulphated polysaccharides. Br. J. Haematol. 64: 707–714.

    Article  PubMed  Google Scholar 

  65. Fernandez, F., van Ryn, J., Ofosu, F.A., Hirsh, J. and Buchanan, M.R. (1986) The haemorrhagic and antithrombotic effects of dermatan sulfate. Br. J. Haematol. 64: 309–317.

    Article  PubMed  CAS  Google Scholar 

  66. Masson, P.J., Coup, D., Millet, J. and Brown, N.L. (1995) The effect of the ß-D-xyloside naroparcil on circulating plasma glycosaminoglycans. An explanation for its known antithrombotic activity in the rabbit. J. Biol. Chem. 270: 2662–2668.

    Article  PubMed  CAS  Google Scholar 

  67. Buchanan, M.R., Liao, P., Smith, L.J. and Ofosu, F.A. (1994) Prevention of thrombus formation and growth by antithrombin III and heparin cofactor II-dependent thrombin inhibitors: importance of heparin cofactor II. Thromb. Res. 74: 463–475.

    CAS  Google Scholar 

  68. Bendayan, P., Boccalon, H., Dupouy, D. and Boneu, B. (1994) Dermatan sulfate is a more potent inhibitor of clot-bound thrombin than unfractionated and low molecular weight heparins. Thromb. Haemost. 71: 576–580.

    CAS  Google Scholar 

  69. Cosmi, B., Agnelli, G., Young, E., Hirsh, J. and Weitz, J. (1993) The additive effect of low molecular weight heparins on thrombin inhibition by dermatan sulfate. Thromb. Haemost. 70: 443–447.

    CAS  Google Scholar 

  70. Lane, D.A., Ryan, K., Ireland, H., Curtis, J.R., Nurmohamed, M.T., Krediet, R.T., Roggekamp, M.C., Stevens, P. and ten Cate, J.W. (1992) Dermatan sulphate in haemodialysis. Lancet 339: 334–335.

    Article  PubMed  CAS  Google Scholar 

  71. Prandoni, P., Meduri, F., Cuppini, S., Toniato, A., Zangrandi, F., Polistena, P., Gianese, F. and MaffeiFaccioli, A. (1992) Dermatan sulphate: a safe approach to prevention of postoperative deep vein thrombosis. Br. J. Surg. 79: 505–509.

    Article  PubMed  CAS  Google Scholar 

  72. Agnelli, G., Cosmi, B., Di Filippo, P., Ranucci, V., Veschi, F., Longetti, M., Renga, C., Barzi, F., Gianese, F., Lupattelli, L., Rinonapoli, E. and Nenci, G.G. (1992) Arandomised, double-blind, placebo-controlled trial of dermatan sulphate for prevention of deep vein thrombosis in hip fracture. Thromb. Haemost. 67: 203–208.

    CAS  Google Scholar 

  73. Andersson, T.R., Sié, P., Pelzer, H., Aamodt, L.-M., Nustad, K. and Abildgaard, U. (1992) Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation. Thromb. Res. 66: 591–598.

    CAS  Google Scholar 

  74. Liu, L., Dewar, L., Song, Y., Kulczycky, M., Blajchman, M.A., Fenton, J.W., II, Andrew, M., Delorme, M., Ginsberg, J., Preissner, K.T. and Ofosu, F.A. (1995) Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo. Thromb. Haemost. 73: 405–412.

    CAS  Google Scholar 

  75. McGuire, E.A. and Tollefsen, D.M. (1987) Activation of heparin cofactor II by fibroblasts and vascular smooth muscle cells. J. Biol. Chem. 262: 169–175.

    PubMed  CAS  Google Scholar 

  76. Hiramoto, S.A. and Cunningham, D.D. (1988) Effects of fibroblasts and endothelial cells on inactivation of target proteases by protease nexin-1, heparin cofactor II, and Cl-inhibitor. J. Cell. Biochem. 36: 199–207.

    Article  PubMed  CAS  Google Scholar 

  77. Whinna, H.C., Choi, H.U., Rosenberg, L.C. and Church, F.C. (1993) Interaction of heparin cofactor II with biglycan and decorin. J. Biol. Chem. 268: 3920–3924.

    PubMed  CAS  Google Scholar 

  78. Andersson, T.R., Larsen, M.L., Handeland, G.F. and Abildgaard, U. (1986) Heparin cofactor II activity in plasma: application of an automated assay method to the study of a normal adult population. Scand. J. Haematol. 36: 96–102.

    CAS  Google Scholar 

  79. Awidi, A.S., Abu-Khalaf, M., Herzallah, U., Abu-Rajab, A., Shannak, M.M., Abu-Obeid, T., Al-Taher, I. and Anshasi, B. (1993) Hereditary thrombophilia among 217 consecutive patients with thromboembolic disease in Jordan. Am. J. Hematol. 44: 95–100.

    Article  PubMed  CAS  Google Scholar 

  80. Sié, P., Dupouy, D., Pichon, J. and Boneu, B. (1985) Constitutional heparin co-factor II deficiency associated with recurrent thrombosis. Lancet 2: 414–416.

    Article  PubMed  Google Scholar 

  81. Tran, T.H., Marbet, G.A. and Duckert, F. (1985) Association of hereditary heparin co-factor II deficiency with thrombosis. Lancet 2: 413–414.

    Article  PubMed  CAS  Google Scholar 

  82. Weisdorf, D.J. and Edson, J.R. (1991) Recurrent venous thrombosis associated with inherited deficiency of heparin cofactor II. Br. J. Haematol. 77: 125–126.

    Article  PubMed  CAS  Google Scholar 

  83. Matsuo, T., Kario, K., Sakamoto, S., Yamada, T., Miki, T., Hirase, T. and Kobayashi, H. (1992) Hereditary heparin cofactor II deficiency and coronary artery disease. Thromb. Res. 65: 495–505.

    CAS  Google Scholar 

  84. Andrew, M., Mitchell, L., Berry, L., Paes, B., Delorme. M., Ofosu, F., Burrows, R. and Khambalia, B. (1992) An anticoagulant dermatan sulfate proteoglycan circulates in the pregnant woman and her fetus. J. Clin. Invest. 89: 321–326.

    CAS  Google Scholar 

  85. Brennan, M.J., Oldberg, A., Pierschbacher, M.D. and Ruoslahti, E. (1984) Chondroitin/dermatan sulfate proteoglycan in human fetal membranes: demonstration of an antigenically similar proteoglycan in fibroblasts. J. Biol. Chem. 259: 13742–13750.

    PubMed  CAS  Google Scholar 

  86. Massouh, M., Jatoi, A., Gordon, E.M. and Ratnoff, O.D. (1989) Heparin cofactor II activity in plasma during pregnancy and oral contraceptive use. J. Lab. Clin. Med. 114: 697–699.

    PubMed  CAS  Google Scholar 

  87. Andersson, T., Lorentzen, B., Hegdahl, H., Clausen, T., Mowinckel, M.-C. and Abildgaard, U. (1996) Thrombin-inhibitor complexes in the blood during and after delivery. Thromb. Res. 82: 109–117.

    CAS  Google Scholar 

  88. Sandset, P.M., Hellgren, M., Uvebrandt, M. and Bergström, H. (1989) Extrinsic coagulation pathway inhibitor and heparin cofactor II during normal and hypertensive pregnancy. Thromb. Res. 55: 665–670.

    CAS  Google Scholar 

  89. Coughlin, S.R., Vu, T.-K.H., Hung, D.T. and Wheaton, V.I. (1992) Characterization of a functional thrombin receptor. Issues and opportunities. J. Clin. Invest. 89: 351–355.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Dr. Douglas M. Tollefsen

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  1. Dr. Douglas M. Tollefsen
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Correspondence to Douglas M. Tollefsen .

Editor information

Editors and Affiliations

  1. University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

    Frank C. Church

  2. University of California, Irvine, California, USA

    Dennis D. Cunningham

  3. Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan, USA

    David Ginsburg

  4. Duke University and Durham VA Medical Centers, Durham, North Carolina, USA

    Maureane Hoffman

  5. Late of Monash University, Clayton, Victoria, Australia

    Stuart R. Stone

  6. Washington University School of Medicine, St. Louis, Missouri, USA

    Douglas M. Tollefsen

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Tollefsen, D.M. (1997). Heparin Cofactor II. In: Church, F.C., Cunningham, D.D., Ginsburg, D., Hoffman, M., Stone, S.R., Tollefsen, D.M. (eds) Chemistry and Biology of Serpins. Advances in Experimental Medicine and Biology, vol 425. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5391-5_4

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