heparin cofactor ii

Summary

Summary: A sulfated plasma protein with a MW of approximately 66kDa that resembles ANTITHROMBIN III. The protein is an inhibitor of thrombin in plasma and is activated by dermatan sulfate or heparin. It is a member of the serpin superfamily.

Top Publications

  1. Mitchell J, Church F. Aspartic acid residues 72 and 75 and tyrosine-sulfate 73 of heparin cofactor II promote intramolecular interactions during glycosaminoglycan binding and thrombin inhibition. J Biol Chem. 2002;277:19823-30 pubmed
    ..Asp(70), Asp(71), Asp(72), Tyr-sulfate(73), and Asp(75) in the second acidic region (AR2) of the serpin heparin cofactor II (HCII) during formation of the thrombin.HCII complex with and without glycosaminoglycans...
  2. Corral J, Aznar J, Gonzalez Conejero R, Villa P, Minano A, Vaya A, et al. Homozygous deficiency of heparin cofactor II: relevance of P17 glutamate residue in serpins, relationship with conformational diseases, and role in thrombosis. Circulation. 2004;110:1303-7 pubmed
    b>Heparin cofactor II (HCII) is a hepatic serpin with significant antithrombin activity that has been implicated in coagulation, inflammation, atherosclerosis, and wound repair...
  3. Tovar A, de Mattos D, Stelling M, Sarcinelli Luz B, Nazareth R, Mourao P. Dermatan sulfate is the predominant antithrombotic glycosaminoglycan in vessel walls: implications for a possible physiological function of heparin cofactor II. Biochim Biophys Acta. 2005;1740:45-53 pubmed
    ..The other, which may assume special relevance after vascular endothelial injury, is based on heparin cofactor II activation by the dermatan sulfate proteoglycans synthesized by cells from the subendothelial layer.
  4. Giri T, Tollefsen D. Placental dermatan sulfate: isolation, anticoagulant activity, and association with heparin cofactor II. Blood. 2006;107:2753-8 pubmed
    Pregnancy is associated with hemostatic challenges that may lead to thrombosis. Heparin cofactor II (HCII) is a glycosaminoglycan-dependent thrombin inhibitor present in both maternal and fetal plasma...
  5. Vicente C, He L, Tollefsen D. Accelerated atherogenesis and neointima formation in heparin cofactor II deficient mice. Blood. 2007;110:4261-7 pubmed
    b>Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin when bound to dermatan sulfate or heparin. HCII-deficient mice are viable and fertile but rapidly develop thrombosis of the carotid artery after endothelial injury...
  6. Sutherland J, Bhakta V, Sheffield W. The appended tail region of heparin cofactor II and additional reactive centre loop mutations combine to increase the reactivity and specificity of alpha1-proteinase inhibitor M358R for thrombin. Thromb Haemost. 2007;98:1014-23 pubmed
    Natural inhibitors of coagulation or inflammation such as the serpins antithrombin (AT), heparin cofactor II (HCII), and alpha(1)-proteinase inhibitor (alpha(1)-PI) can be overwhelmed in thrombosis and/or sepsis...
  7. Tollefsen D. Vascular dermatan sulfate and heparin cofactor II. Prog Mol Biol Transl Sci. 2010;93:351-72 pubmed publisher
    b>Heparin cofactor II (HCII) is a plasma protease inhibitor of the serpin family that inactivates thrombin by forming a covalent 1:1 complex...
  8. Ikeda Y, Aihara K, Yoshida S, Iwase T, Tajima S, Izawa Ishizawa Y, et al. Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway. J Biol Chem. 2012;287:34256-63 pubmed publisher
    We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies...
  9. Hortin G, Tollefsen D, Strauss A. Identification of two sites of sulfation of human heparin cofactor II. J Biol Chem. 1986;261:15827-30 pubmed
    Tyrosine sulfate was identified as a constituent of human heparin cofactor II by analysis of sulfate-labeled protein secreted by a human hepatoma-derived cell line and of purified protein from human plasma...

More Information

Publications62

  1. Singh S, Papareddy P, Kalle M, Schmidtchen A, Malmsten M. Importance of lipopolysaccharide aggregate disruption for the anti-endotoxic effects of heparin cofactor II peptides. Biochim Biophys Acta. 2013;1828:2709-19 pubmed publisher
    ..LPS) interactions were investigated for a series of amphiphilic and cationic peptides derived from human heparin cofactor II (HCII), using dual polarization interferometry, ellipsometry, circular dichroism (CD), cryoTEM, and z-..
  2. Pavão M, Mourao P, Mulloy B, Tollefsen D. A unique dermatan sulfate-like glycosaminoglycan from ascidian. Its structure and the effect of its unusual sulfation pattern on anticoagulant activity. J Biol Chem. 1995;270:31027-36 pubmed
    ..Mammalian dermatan sulfate is an anticoagulant due to its ability to potentiate inhibition of thrombin by heparin cofactor II. The structure in dermatan sulfate which binds to heparin cofactor II is [4-alpha-L-IdoA-(2SO4)-1-->3-..
  3. Randall D, Colobong K, Hemmelgarn H, Sinclair G, Hetty E, Thomas A, et al. Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab. 2008;94:456-61 pubmed publisher
    ..We show that serum levels of heparin cofactor II-thrombin complex is a reliable biomarker of the mucopolysaccharidoses...
  4. Papareddy P, Kalle M, Singh S, Morgelin M, Schmidtchen A, Malmsten M. An antimicrobial helix A-derived peptide of heparin cofactor II blocks endotoxin responses in vivo. Biochim Biophys Acta. 2014;1838:1225-34 pubmed publisher
    ..Here, we describe that the peptide GKS26 (GKSRIQRLNILNAKFAFNLYRVLKDQ), corresponding to the A domain of heparin cofactor II (HCII), ameliorates experimental septic shock...
  5. Church F, Pratt C, Hoffman M. Leukocyte chemoattractant peptides from the serpin heparin cofactor II. J Biol Chem. 1991;266:704-9 pubmed
    b>Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits the coagulant proteinase alpha-thrombin...
  6. Pratt C, Tobin R, Church F. Interaction of heparin cofactor II with neutrophil elastase and cathepsin G. J Biol Chem. 1990;265:6092-7 pubmed
    We investigated the interaction of the human plasma proteinase inhibitor heparin cofactor II (HC) with human neutrophil elastase and cathepsin G in order to examine 1) proteinase inhibition by HC, 2) inactivation of HC, and 3) the effect ..
  7. Hortin G, Tollefsen D, Benutto B. Antithrombin activity of a peptide corresponding to residues 54-75 of heparin cofactor II. J Biol Chem. 1989;264:13979-82 pubmed
    b>Heparin cofactor II (HCII) is a highly specific serine proteinase inhibitor, which complexes covalently with thrombin in a reaction catalyzed by heparin and other polyanions...
  8. He L, Giri T, Vicente C, Tollefsen D. Vascular dermatan sulfate regulates the antithrombotic activity of heparin cofactor II. Blood. 2008;111:4118-25 pubmed publisher
    b>Heparin cofactor II (HCII)-deficient mice form occlusive thrombi more rapidly than do wild-type mice following injury to the carotid arterial endothelium...
  9. Hayakawa Y, Hirashima Y, Kurimoto M, Hayashi N, Hamada H, Kuwayama N, et al. Contribution of basic residues of the A helix of heparin cofactor II to heparin- or dermatan sulfate-mediated thrombin inhibition. FEBS Lett. 2002;522:147-50 pubmed
    Inhibition of thrombin by heparin cofactor II (HCII) is accelerated 1000-fold by heparin or dermatan sulfate...
  10. Pavão M. Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates. An Acad Bras Cienc. 2002;74:105-12 pubmed
    ..acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity...
  11. Sumitomo Ueda Y, Aihara K, Ise T, Yoshida S, Ikeda Y, Uemoto R, et al. Heparin cofactor II protects against angiotensin II-induced cardiac remodeling via attenuation of oxidative stress in mice. Hypertension. 2010;56:430-6 pubmed publisher
    b>Heparin cofactor II (HCII), a serine protease inhibitor, inhibits tissue thrombin action after binding with dermatan sulfate proteoglycans in the extracellular matrix of the vascular system...
  12. He L, Vicente C, Westrick R, Eitzman D, Tollefsen D. Heparin cofactor II inhibits arterial thrombosis after endothelial injury. J Clin Invest. 2002;109:213-9 pubmed
    b>Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin rapidly in the presence of dermatan sulfate, heparan sulfate, or heparin...
  13. Liaw P, Becker D, Stafford A, Fredenburgh J, Weitz J. Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation by heparin cofactor ii in the presence of dermatan sulfate but not heparin. J Biol Chem. 2001;276:20959-65 pubmed
    Although fibrin-bound thrombin is resistant to inactivation by heparin.antithrombin and heparin.heparin cofactor II complexes, indirect studies in plasma systems suggest that the dermatan sulfate...
  14. Liu L, Dewar L, Song Y, Kulczycky M, Blajchman M, Fenton J, et al. Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo. Thromb Haemost. 1995;73:405-12 pubmed
    ..Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital ..
  15. Langford Smith K, Arasaradnam M, Wraith J, Wynn R, Bigger B. Evaluation of heparin cofactor II-thrombin complex as a biomarker on blood spots from mucopolysaccharidosis I, IIIA and IIIB mice. Mol Genet Metab. 2010;99:269-74 pubmed publisher
    ..Serum heparin cofactor II-thrombin complex (HCII-T), which is a GAG regulated serpin-protease complex, has recently been identified ..
  16. Vicente C, He L, Pavão M, Tollefsen D. Antithrombotic activity of dermatan sulfate in heparin cofactor II-deficient mice. Blood. 2004;104:3965-70 pubmed
    b>Heparin cofactor II (HCII) is a plasma protein that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin...
  17. Halldórsdóttir A, Zhang L, Tollefsen D. N-Acetylgalactosamine 4,6-O-sulfate residues mediate binding and activation of heparin cofactor II by porcine mucosal dermatan sulfate. Glycobiology. 2006;16:693-701 pubmed
    Dermatan sulfate (DS) accelerates the inhibition of thrombin by heparin cofactor II (HCII)...
  18. Randall D, Sinclair G, Colobong K, Hetty E, Clarke L. Heparin cofactor II-thrombin complex in MPS I: a biomarker of MPS disease. Mol Genet Metab. 2006;88:235-43 pubmed
    ..Using proteomic studies in the murine MPS I model, we have identified the formation of the heparin cofactor II-thrombin (HCII-T) complex, a well-known serine protease inhibitor (serpin)-serine protease complex, as an ..
  19. Pomin V, Pereira M, Valente A, Tollefsen D, Pavão M, Mourao P. Selective cleavage and anticoagulant activity of a sulfated fucan: stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, preparation of oligosaccharides, and heparin cofactor II-dependent anticoagulant activity. Glycobiology. 2005;15:369-81 pubmed
    ..is an anticoagulant polysaccharide mainly due to thrombin inhibition mediated by heparin cofactor II. No specific enzymatic or chemical method is available for the preparation of tailored oligosaccharides ..
  20. Filion M, Bhakta V, Nguyen L, Liaw P, Sheffield W. Full or partial substitution of the reactive center loop of alpha-1-proteinase inhibitor by that of heparin cofactor II: P1 Arg is required for maximal thrombin inhibition. Biochemistry. 2004;43:14864-72 pubmed
    ..In contrast to either the wild-type or M358R alpha(1)-PI, heparin cofactor II (HCII) is a IIa-specific inhibitor with an atypical Leu-Ser reactive center...
  21. Brinkmeyer S, Eckert R, Ragg H. Reformable intramolecular cross-linking of the N-terminal domain of heparin cofactor II: effects on enzyme inhibition. Eur J Biochem. 2004;271:4275-83 pubmed
    The crystal structure of a heparin cofactor II (HCII)-thrombin Michaelis complex has revealed extensive contacts encompassing the N-terminal domain of HCII and exosite I of the proteinase...
  22. Kalle M, Papareddy P, Kasetty G, Tollefsen D, Malmsten M, Morgelin M, et al. Proteolytic activation transforms heparin cofactor II into a host defense molecule. J Immunol. 2013;190:6303-10 pubmed publisher
    The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic...
  23. Van Deerlin V, Tollefsen D. The N-terminal acidic domain of heparin cofactor II mediates the inhibition of alpha-thrombin in the presence of glycosaminoglycans. J Biol Chem. 1991;266:20223-31 pubmed
    b>Heparin cofactor II (HCII) is a glycoprotein in human plasma that inhibits thrombin and chymotrypsin...
  24. Aihara K, Azuma H, Takamori N, Kanagawa Y, Akaike M, Fujimura M, et al. Heparin cofactor II is a novel protective factor against carotid atherosclerosis in elderly individuals. Circulation. 2004;109:2761-5 pubmed
    Thrombin plays a crucial role in atherothrombotic changes. Because heparin cofactor II (HCII) inhibits thrombin actions after binding to dermatan sulfate at injured arterial walls, HCII may negatively regulate thrombin actions in ..
  25. Bernardi F, Legnani C, Micheletti F, Lunghi B, Ferraresi P, Palareti G, et al. A heparin cofactor II mutation (HCII Rimini) combined with factor V Leiden or type I protein C deficiency in two unrelated thrombophilic subjects. Thromb Haemost. 1996;76:505-9 pubmed
    305 patients with juvenile thromboembolic episodes were screened for the presence of heparin cofactor II deficiency...
  26. Fortenberry Y, Whinna H, Gentry H, Myles T, Leung L, Church F. Molecular mapping of the thrombin-heparin cofactor II complex. J Biol Chem. 2004;279:43237-44 pubmed
    ..thrombin molecules to define residues important for inhibition by the serine protease inhibitor (serpin) heparin cofactor II (HCII) in the absence and presence of glycosaminoglycans...
  27. RAU J, Mitchell J, Fortenberry Y, Church F. Heparin cofactor II: discovery, properties, and role in controlling vascular homeostasis. Semin Thromb Hemost. 2011;37:339-48 pubmed publisher
    b>Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) found in high concentrations in human plasma. Despite its discovery >30 years ago, its physiological function is still poorly understood...
  28. Vicente C, Zancan P, Peixoto L, Alves Sá R, Araújo F, Mourao P, et al. Unbalanced effects of dermatan sulfates with different sulfation patterns on coagulation, thrombosis and bleeding. Thromb Haemost. 2001;86:1215-20 pubmed
    ..acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity...
  29. Cunningham M, Bhakta V, Sheffield W. Altering heparin cofactor II at VAL439 (P6) either impairs inhibition of thrombin or confers elastase resistance. Thromb Haemost. 2002;88:89-97 pubmed
    b>Heparin cofactor II (HCII) is plasma glycoprotein and thrombin inhibitor of the serpin type previously shown to inhibit thrombin in the absence of its N-terminal 74 amino acids, and to be cleaved by neutrophil elastase (NE) at two sites: ..
  30. Baglin T, Carrell R, Church F, Esmon C, Huntington J. Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc Natl Acad Sci U S A. 2002;99:11079-84 pubmed
    ..mobility of serpins is demonstrated here by the structures of native and S195A thrombin-complexed heparin cofactor II (HCII)...
  31. Sutherland J, Bhakta V, Filion M, Sheffield W. The transferable tail: fusion of the N-terminal acidic extension of heparin cofactor II to alpha1-proteinase inhibitor M358R specifically increases the rate of thrombin inhibition. Biochemistry. 2006;45:11444-52 pubmed
    ..Another serpin, heparin cofactor II (HCII), contains a unique N-terminal extension that binds thrombin exosite 1...
  32. Herzog R, Lutz S, Blin N, Marasa J, Blinder M, Tollefsen D. Complete nucleotide sequence of the gene for human heparin cofactor II and mapping to chromosomal band 22q11. Biochemistry. 1991;30:1350-7 pubmed
    b>Heparin cofactor II (HCII) is a 66-kDa plasma glycoprotein that inhibits thrombin rapidly in the presence of dermatan sulfate or heparin...
  33. Huang P, Leu H, Chen J, Wu T, Lu T, Yu An Ding P, et al. Decreased heparin cofactor II activity is associated with impaired endothelial function determined by brachial ultrasonography and predicts cardiovascular events. Int J Cardiol. 2007;114:152-8 pubmed
    b>Heparin cofactor II (HCII) could inactivate thrombin after binding to dermatan sulfate at injured arterial walls, and has been shown to be a novel and independent antiatherosclerotic factor...
  34. Eckert R, Ragg H. Zinc ions promote the interaction between heparin and heparin cofactor II. FEBS Lett. 2003;541:121-5 pubmed
    The effects of bivalent cations on heparin binding, structure, and thrombin inhibition rates of heparin cofactor II were examined...
  35. Blinder M, Tollefsen D. Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. J Biol Chem. 1990;265:286-91 pubmed
    ..These results provide evidence that the glycosaminoglycan-binding site in HCII includes Lys185 but not Arg103, both of which were predicted to be involved by homology to anti-thrombin. ..
  36. Takamori N, Azuma H, Kato M, Hashizume S, Aihara K, Akaike M, et al. High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention. Circulation. 2004;109:481-6 pubmed
    ..Because heparin cofactor II (HCII) inhibits thrombin action in the presence of dermatan sulfate, which is abundantly present in ..
  37. Verhamme I, Bock P, Jackson C. The preferred pathway of glycosaminoglycan-accelerated inactivation of thrombin by heparin cofactor II. J Biol Chem. 2004;279:9785-95 pubmed
    Thrombin (T) inactivation by the serpin, heparin cofactor II (HCII), is accelerated by the glycosaminoglycans (GAGs) dermatan sulfate (DS) and heparin (H). Equilibrium binding and thrombin inactivation kinetics at pH 7...
  38. Langford Smith K, Mercer J, Petty J, Tylee K, Church H, Roberts J, et al. Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases. J Inherit Metab Dis. 2011;34:499-508 pubmed publisher
    ..We evaluate heparin cofactor II-thrombin complex (HCII-T) as a biomarker in serum and dried blood spots (DBS) of MPS patients...
  39. RAU J, Deans C, Hoffman M, Thomas D, Malcom G, Zieske A, et al. Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Exp Mol Pathol. 2009;87:178-83 pubmed publisher
    b>Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice...
  40. Yoon S, Pereira M, Pavão M, Hwang J, Pyun Y, Mourao P. The medicinal plant Porana volubilis contains polysaccharides with anticoagulant activity mediated by heparin cofactor II. Thromb Res. 2002;106:51-8 pubmed
    ..anticoagulant activity is mediated by the enhancement of thrombin inhibition that in turn is mediated by heparin cofactor II but not by antithrombin...
  41. Rahgozar S, Giannakopoulos B, Yan X, Wei J, Cheng Qi J, Gemmell R, et al. Beta2-glycoprotein I protects thrombin from inhibition by heparin cofactor II: potentiation of this effect in the presence of anti-beta2-glycoprotein I autoantibodies. Arthritis Rheum. 2008;58:1146-55 pubmed publisher
    ..present study was undertaken to examine the influence of beta2GPI on thrombin inactivation by the serpin heparin cofactor II (HCII). The effect of anti-beta2GPI antibodies was also examined...
  42. Tollefsen D. Heparin cofactor II deficiency. Arch Pathol Lab Med. 2002;126:1394-400 pubmed
    To review of the state of the art relating to congenital heparin cofactor II deficiency as a potential risk factor for thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and ..
  43. Ben Mansour M, Dhahri M, Venisse L, Jandrot Perrus M, Chaubet F, Maaroufi R. Mechanism of thrombin inhibition by heparin cofactor II and antithrombin in the presence of the ray (Raja radula) skin dermatan sulfate. Thromb Res. 2009;123:902-8 pubmed publisher
    The kinetics of the thrombin inhibition by heparin cofactor II (HCII) and antithrombin (AT) have been studied as a function of the concentration of a dermatan sulfate (DS) from the skin of the ray Raja radula...
  44. Suwan J, Zhang Z, Li B, Vongchan P, Meepowpan P, Zhang F, et al. Sulfonation of papain-treated chitosan and its mechanism for anticoagulant activity. Carbohydr Res. 2009;344:1190-6 pubmed publisher
    ..the molecular binding of sulfated chitosan to two important blood clotting regulators, antithrombin III and heparin cofactor II. These results show that the principal mechanism by which this chitosan polysulfate exhibits anticoagulant ..
  45. Mao W, Li H, Li Y, Zhang H, Qi X, Sun H, et al. Chemical characteristic and anticoagulant activity of the sulfated polysaccharide isolated from Monostroma latissimum (Chlorophyta). Int J Biol Macromol. 2009;44:70-4 pubmed publisher
    ..The anticoagulant property of the sulfated polysaccharide was mainly attributed to powerful potentiation thrombin by heparin cofactor II.
  46. Hayakawa Y, Hirashima Y, Yamamoto H, Kurimoto M, Hayashi T, Lee J, et al. Mechanism of activation of heparin cofactor II by calcium spirulan. Arch Biochem Biophys. 2003;416:47-52 pubmed
    Calcium spirulan (Ca-SP), a novel sulfated polysaccharide, increases the rate of thrombin inhibition by heparin cofactor II (HCII) more than 1000-fold through a mechanism not requiring the amino-terminal acidic domain of HCII...
  47. Weitz J, Young E, Johnston M, Stafford A, Fredenburgh J, Hirsh J. Vasoflux, a new anticoagulant with a novel mechanism of action. Circulation. 1999;99:682-9 pubmed
    ..Vasoflux catalyzes fibrin-bound thrombin inactivation by heparin cofactor II (HCII) and inhibits factor IXa activation of factor X independently of antithrombin and HCII...
  48. Berry L, Klement P, Andrew M, Chan A. Effect of covalent serpin-heparinoid complexes on plasma thrombin generation on fetal distal lung epithelium. Am J Respir Cell Mol Biol. 2003;28:150-8 pubmed
    ..However, heparin cofactor II (HC) has been shown to selectively inhibit thrombin, which may be advantageous if other enzyme activities ..
  49. Verhamme I. Fluorescent reporters of thrombin, heparin cofactor II, and heparin binding in a ternary complex. Anal Biochem. 2012;421:489-98 pubmed publisher
    Thrombin inactivation by heparin cofactor II (HCII) is accelerated by ternary complex formation with heparin...
  50. Gray E, Hogwood J, Mulloy B. The anticoagulant and antithrombotic mechanisms of heparin. Handb Exp Pharmacol. 2012;:43-61 pubmed publisher
    ..The antithrombotic action of heparin in vivo, though dominated by anticoagulant mechanisms, is more complex, and interactions with other plasma proteins and cells play significant roles in the living vasculature. ..
  51. Sheehan J, Lan H. Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex. Blood. 1998;92:1617-25 pubmed
    ..high concentrations of ISIS 2302 inhibited thrombin clotting activity both by stimulating inhibition by heparin cofactor II and directly competing with fibrinogen for binding to anion binding exosite I...
  52. Pereira M, Vilela Silva A, Valente A, Mourao P. A 2-sulfated, 3-linked alpha-L-galactan is an anticoagulant polysaccharide. Carbohydr Res. 2002;337:2231-8 pubmed
    ..alpha-L-galactan, but not an alpha-L-fucan, is a potent thrombin inhibitor mediated by antithrombin or heparin cofactor II. The difference between the activities of these two polysaccharides is not very pronounced when factor Xa ..
  53. Hanumanthaiah R, Day K, Jagadeeswaran P. Comprehensive analysis of blood coagulation pathways in teleostei: evolution of coagulation factor genes and identification of zebrafish factor VIIi. Blood Cells Mol Dis. 2002;29:57-68 pubmed