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Blood Coagulation

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Abstract

The process of tissue factor initiated blood coagulation is discussed. Reactions of the blood coagulation cascade are propagated by complex enzymes containing a vitamin K-dependent serine protease and an accessory cofactor protein that are assembled on a membrane surface in a calcium-dependent manner.These complexes are 105 109-fold more efficient in proteolyses of their natural substrates than enzymes alone. Based upon data acquired using several in vitro models of blood coagulation, tissue factor initiated thrombin generation can be divided into two phases: an initiation phase and a propagation phase. The initiation phase is characterized by the generation of nanomolar amounts of thrombin, femto- to picomolar amounts of factors VIIa, IXa, Xa, and XIa, partial activation of platelets, and almost quantitative activation of procofactors, factors V and VIII. The duration of this phase is primarily influenced by concentrations of tissue factor and TFPI. The characteristic features of the propagation phase are: almost quantitative prothrombin activation at a high rate, completion of platelet activation, and solid clot formation. This phase is primarily regulated by antithrombin III and the protein C system. Thrombin generation during the propagation phase is remarkably suppressed in the absence of factor VIII and IX (hemophilia A and B, respectively) and at platelet counts <5% of mean plasma concentration. The majority of data accumulated in in vitro models and discussed in this review are in good agreement with the results of in vivo observations.

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REFERENCES

  1. Wilcox, J. N., Smith, K. M., Schwartz, S. M., and Gordon, D. (1989) Proc. Natl. Acad. Sci. USA, 86, 2839-2843.

    Google Scholar 

  2. Weiss, H. J., Turitto, V. T., Maumgartner, H. R., Nemerson, Y., and Hoffmann, T. (1989) Blood, 73, 968-975.

    Google Scholar 

  3. Carlsen, E., Flatmark, A., and Prydz, H. (1988) Transplantation, 46, 575-580.

    Google Scholar 

  4. Bevilaqua, M. P., Pober, J. S., Majeau, G. R., et al. (1986) Proc. Natl. Acad. Sci. USA, 83, 4533-4537.

    Google Scholar 

  5. Yang, H. L., Lu, F. J., Wung, S. L., et al. (1994) Thromb. Haemost., 71, 325-330.

    Google Scholar 

  6. Camera, M., Giesen, P. L., Fallon, J., et al. (1999) Arterioscler. Thromb. Vasc. Biol., 19, 531-537.

    Google Scholar 

  7. Morrissey, J. H., Macik, B. G., Neuenschwander, P. F., et al. (1993) Blood, 81, 734-744.

    Google Scholar 

  8. Eichinger, S., Mannucci, P. M., Tradati, F., et al. (1995) Blood, 86, 3021-3025.

    Google Scholar 

  9. Silverberg, S. A., Nemerson, Y., and Zur, M. (1977) J. Biol. Chem., 252, 8481-8488.

    Google Scholar 

  10. Komiyama, Y., Pedersen, A. H., and Kisiel, W. (1990) Biochemistry, 29, 9418-9425.

    Google Scholar 

  11. Bom, V. J. J., and Bertina, R. M. (1990) Biochem. J., 265, 327-336.

    Google Scholar 

  12. Lawson, J. H., and Mann, K. G. (1991) J. Biol. Chem., 266, 11317-11327.

    Google Scholar 

  13. Lawson, J. H., Kalafatis, M., Stram, S., and Mann, K. G. (1994) J. Biol. Chem., 269, 23357-23366.

    Google Scholar 

  14. Rand, M. D., Lock, J. B., van 't Veer, C., Gaffney, D. P., and Mann, K. G. (1996) Blood, 88, 3432-3445.

    Google Scholar 

  15. Butenas, S., van 't Veer, C., and Mann, K. G. (1997) J. Biol. Chem., 272, 21527-21533.

    Google Scholar 

  16. Rosing, J., van Rijn, J. L. M. L., Bevers, E. M., van Dieijen, G., Comfurius, P., and Zwaal, R. F. (1985) Blood, 65, 319-332.

    Google Scholar 

  17. Tans, G., Rosing, J., Thomassen, M. C., Heeb, M. J., Zwaal, R. F., and Griffin, J. H. (1991) Blood, 77, 2641-2648.

    Google Scholar 

  18. Hugel, B., Socie, G., Vu, T., et al. (1999) Blood, 93, 3451-3456.

    Google Scholar 

  19. Stern, D., Nawroth, P., Handley, D., and Kisiel, W. (1985) Proc. Natl. Acad. Sci. USA, 82, 2523-2527.

    Google Scholar 

  20. Mann, K. G., Krishnaswamy, S., and Lawson, J. H. (1992) Sem. Hematol., 29, 213-226.

    Google Scholar 

  21. Ahmad, S. S., Rawala-Sheikh, R., and Walsh, P. N. (1992) Sem. Thromb. Hemost., 18, 311-323.

    Google Scholar 

  22. Papahadjopoulos, D., and Hanahan, D. J. (1964) Biochim. Biophys. Acta, 90, 436-439.

    Google Scholar 

  23. Nesheim, M. E., Taswell, J. B., and Mann, K. G. (1979) J. Biol. Chem., 254, 10952-10962.

    Google Scholar 

  24. Kalafatis, M., Swords, N. A., Rand, M. D., et al. (1994) Biochim. Biophys. Acta, 1227, 113-129.

    Google Scholar 

  25. Gailani, D., and Broze, G. J., Jr. (1991) Science, 253, 909-912.

    Google Scholar 

  26. Pieters, J., Lindhout, T., and Hemker, H. C. (1989) Blood, 74, 1021-1024.

    Google Scholar 

  27. Mosesson, M. W. (1992) Sem. Hematol., 29, 177-188.

    Google Scholar 

  28. Bailey, K., Bettelheim, F. R., Lorand, L., et al. (1951) Nature, 167, 233-234.

    Google Scholar 

  29. Lorand, L., and Konishi, K. (1964) Arch. Biochem. Biophys., 105, 58-67.

    Google Scholar 

  30. Naski, M. C., Lorand, L., and Shafer, J. A. (1991) Biochemistry, 30, 934-941.

    Google Scholar 

  31. Shen, L., and Lorand, L. (1983) J. Clin. Invest., 71, 1336-1341.

    Google Scholar 

  32. Brummel, K. E., Butenas, S., and Mann, K. G. (1999) J. Biol. Chem., 274, 22862-22870.

    Google Scholar 

  33. Olson, S. T., Bjork, I., and Shore, J. D. (1993) Meth. Enzymol., 222, 525-559.

    Google Scholar 

  34. Nowotny, W. F., Brown, S. G., Miletich, J. P., et al. (1991) Blood, 78, 387-393.

    Google Scholar 

  35. Girard, T. J., Warren, L. A., Novotny, W. F., et al. (1989) Nature, 338, 518-520.

    Google Scholar 

  36. Rapaport, S. I. (1991) Thromb. Haemost., 66, 6-15.

    Google Scholar 

  37. Broze, G. J., Jr., Warren, L. A., Novotny, W. F., et al. (1988) Blood, 71, 335-343.

    Google Scholar 

  38. Esmon, N. L., Owen, W. G., and Esmon, C. T. (1982) J. Biol. Chem., 257, 859-864.

    Google Scholar 

  39. Esmon, C. T., Esmon, N. L., Bonniec, B. F., et al. (1993) Meth. Enzymol., 222, 359-385.

    Google Scholar 

  40. Walker, F. J., Sexton, P. W., and Esmon, C. T. (1979) Biochim. Biophys. Acta, 571, 333-342.

    Google Scholar 

  41. Suzuki, K., Stenflo, J., Dahlback, B., et al. (1983) J. Biol. Chem., 258, 1914-1920.

    Google Scholar 

  42. Hockin, M. F., Kalafatis, M., Shatos, M., and Mann, K. G. (1997) Arterioscler. Thromb. Vasc. Biol., 17, 2765-2775.

    Google Scholar 

  43. Eaton, D., Rodriguez, H., and Vehar, G. A. (1986) Biochemistry, 25, 505-512.

    Google Scholar 

  44. Esmon, C. T. (1987) Science, 235, 1348-1352.

    Google Scholar 

  45. Hackeng, T. M., van 't Veer, C., Meijers, J. C. M., and Bouma, B. N. (1994) J. Biol. Chem., 269, 21051-21058.

    Google Scholar 

  46. Koppelman, S. J., van 't Veer, C., Sixma, J. J., and Bouma, B. N. (1995) Blood, 86, 2653-2660.

    Google Scholar 

  47. Van 't Veer, C., Butenas, S., Golden, N. J., and Mann, K. G. (1999) Thromb. Haemost., 82, 80-87.

    Google Scholar 

  48. Lollar, P., and Parker, C. G. (1990) J. Biol. Chem., 265, 1688-1692.

    Google Scholar 

  49. Fay, P. J., Haidaris, P. J., and Smudzin, T. M. (1991) J. Biol. Chem., 266, 8957-8962.

    Google Scholar 

  50. Lu, D., Kalafatis, M., Mann, K. G., et al. (1997) Blood, 87, 4708-4717.

    Google Scholar 

  51. Pipe, S. W., Saenko, E. L., Eickhorst, A. N., Kemball-Cook, G., and Kaufman, R. J. (2001) Blood, 97, 685-691.

    Google Scholar 

  52. Kalafatis, M., Egan, J. O., van 't Veer, C., Cawthern, K. M., and Mann, K. G. (1997) Crit. Rev. Eukaryot. Gene Expr., 7, 241-280.

    Google Scholar 

  53. Seegers, W. H. (1949) Proc. Soc. Exptl. Biol. Med., 72, 677-680.

    Google Scholar 

  54. Mann, K. G., Nesheim, M., Church, W., Haley, P., and Krishnaswamy, S. (1990) Blood, 76, 1-16.

    Google Scholar 

  55. Tracy, P. B., Nesheim, M. E., and Mann, K. G. (1981) J. Biol. Chem., 256, 743-751.

    Google Scholar 

  56. Lamphear, B. J., and Fay, P. J. (1992) J. Biol. Chem., 267, 3725-3730.

    Google Scholar 

  57. Nelsestuen, G. L., Kisiel, W., and DiScipio, R. G. (1978) Biochemistry, 17, 2134-2138.

    Google Scholar 

  58. Hoffman, M., Monroe, D. M., Oliver, J. A., and Roberts, H. R. (1995) Blood, 86, 1794-1801.

    Google Scholar 

  59. Kjalke, M., Oliver, J. A., Monroe, D. M., et al. (1997) Thromb. Haemost., 78, 1202-1208.

    Google Scholar 

  60. Kjalke, M., Monroe, D., Hoffman, M., et al. (1998) Thromb. Haemost., 80, 578-584.

    Google Scholar 

  61. Jones, K. C., and Mann, K. G. (1994) J. Biol. Chem., 269, 23367-23373.

    Google Scholar 

  62. Beltrami, E., and Jesty, J. (1995) Proc. Natl. Acad. Sci. USA, 92, 8744-8748.

    Google Scholar 

  63. Kirchhofer, D., Tschopp, T. B., and Baumgartner, H. R. (1995) Arterioscler. Thromb. Vasc. Biol., 15, 1098-1106.

    Google Scholar 

  64. Peyrou, V., Lormeau, J. C., Herault, J. P., et al. (1999) Thromb. Haemost., 81, 400-406.

    Google Scholar 

  65. Doggen, C. J., Cats, V. M., Bertina, R. M., and Rosendaal, F. R. (1998) Circulation, 97, 1037-1041.

    Google Scholar 

  66. Chiu, H. C., Whitaker, E., and Colman, R. W. (1983) J. Clin. Invest., 72, 493-503.

    Google Scholar 

  67. Poort, S. R., Michiels, J. J., Reitsma, P. H., and Bertina, R. M. (1994) Thromb. Haemost., 72, 819-824.

    Google Scholar 

  68. Ragni, M. V., Lewis, J. H., Spero, J. A., and Hasiba, U. (1981) Am. J. Hematol., 10, 79-88.

    Google Scholar 

  69. Hoyer, L. W. (1994) N. Engl. J. Med., 330, 38-47.

    Google Scholar 

  70. Ozsoylu, S., and Ozer, F. L. (1973) Acta Haematol., 50, 305-314.

    Google Scholar 

  71. Coller, B. S., Owen, J., Jesty, J., et al. (1987) Arteriosclerosis, 7, 456-462.

    Google Scholar 

  72. Woodward, M., Lowe, G. D., Rumley, A., et al. (1997) Br. J. Haematol., 97, 785-797.

    Google Scholar 

  73. Harrison, L., Johnston, M., Massicotte, P., et al. (1997) Ann. Int. Med., 126, 133-136.

    Google Scholar 

  74. Bertina, R. M., Koeleman, B. P., Koster, T., et al. (1994) Nature, 369, 64-67.

    Google Scholar 

  75. Cawthern, K. M., van 't Veer, C., Lock, J. B., DiLorenzo, M. E., Branda, R. F., and Mann, K. G. (1998) Blood, 91, 4581-4592.

    Google Scholar 

  76. Van 't Veer, C., and Mann, K. G. (1997) J. Biol. Chem., 272, 4367-4377.

    Google Scholar 

  77. Van 't Veer, C., Golden, N. J., Kalafatis, M., and Mann, K. G. (1997) J. Biol. Chem., 272, 7983-7994.

    Google Scholar 

  78. Kalafatis, M., Rand, M. D., and Mann, K. G. (1994) J. Biol. Chem., 269, 31869-31880.

    Google Scholar 

  79. Hockin, M. F., Cawthern, K. M., Kalafatis, M., and Mann, K. G. (1999) Biochemistry, 38, 6918-6934.

    Google Scholar 

  80. Butenas, S., van 't Veer, C., and Mann, K. G. (1999) Blood, 94, 2169-2178.

    Google Scholar 

  81. Poort, S. R., Rosendaal, F. R., Reitsma, P. H., and Bertina, R. M. (1996) Blood, 88, 3698-3703.

    Google Scholar 

  82. Van 't Veer, C., Kalafatis, M., Bertina, R. M., Simioni, P., and Mann, K. G. (1997) J. Biol. Chem., 272, 20721-20729.

    Google Scholar 

  83. Kalafatis, M., Bertina, R. M., Rand, M. D., and Mann, K. G. (1995) J. Biol. Chem., 270, 4053-4057.

    Google Scholar 

  84. Van 't Veer, C., Golden, N. J., Kalafatis, M., Simioni, P., Bertina, R. M., and Mann, K. G. (1997) Blood, 90, 3067-3072.

    Google Scholar 

  85. Shapiro, S. S., and Hultin, M. (1975) Sem. Thromb. Hemost., 1, 336-385.

    Google Scholar 

  86. Lusher, J. M., Arkin, S., Abildgaard, C. F., and Schwartz, R. S. (1993) N. Engl. J. Med., 328, 453-459.

    Google Scholar 

  87. Nicolaisen, E. M., Hansen, L. L., Poulsen, F., Glazer, S., and Hedner, U. (1996) Thromb. Haemost., 76, 200-204.

    Google Scholar 

  88. Hedner, U. (2000) Sem. Thromb. Hemost., 26, 363-366.

    Google Scholar 

  89. Shapiro, A. D., Gilchrist, G. S., Hoots, W. K., Cooper, H. A., and Gastineau, D. A. (1998) Thromb. Haemost., 80, 773-778.

    Google Scholar 

  90. Ingerslev, J. (2000) Sem. Thromb. Hemost., 26, 425-432.

    Google Scholar 

  91. Butenas, S., Brummel, K. E., Branda, R. F., and Mann, K. G. (2000) Blood, 96, 2290 (abstract).

    Google Scholar 

  92. Walsh, P. N. (1992) Sem. Hematol., 29, 189-201.

    Google Scholar 

  93. Bolton-Maggs, P. H. B. (1996) Baillieres Clin. Hematol., 9, 355-368.

    Google Scholar 

  94. Butenas, S., Brummel, K. E., and Mann, K. G. (2001) Abst. XVIII Congr. of the ISTH.

  95. Walsh, P. N. (1974) Blood, 43, 597-605.

    Google Scholar 

  96. Hartwig, J. H. (1998) Thrombosis and Hemorrhage (Loscalzo, J., and Schafer, A. I., eds.) Williams and Wilkins, Baltimore, MD, pp. 207-228.

    Google Scholar 

  97. Rutherford, C. J., and Frenkel, E. P. (1994) Med. Clin. North. Am., 78, 555-575.

    Google Scholar 

  98. Miescher, P. A. (1973) Sem. Hematol., 10, 311-325.

    Google Scholar 

  99. Butenas, S., Branda, R. F., van 't Veer, C., Cawthern, K. M., and Mann, K. G. (2001) Thromb. Haemost., 86, 660-667.

    Google Scholar 

  100. Beutler, E. (1993) Blood, 81, 1411-1413.

    Google Scholar 

  101. Roy, A. J., Jaffe, N., and Djerassi, I. (1973) Transfusion, 13, 283-290.

    Google Scholar 

  102. Butenas, S., Cawthern, K. M., van 't Veer, C., DiLorenzo, M., Lock, J. B., and Mann, K. G. (2001) Blood, 97, 2314-2322.

    Google Scholar 

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  1. Department of Biochemistry, University of Vermont, Burlington, VT, 05405 0068, USA

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Butenas, S., Mann, K.G. & Butenas Blood Coagulation. Biochemistry (Moscow) 67, 3–12 (2002). https://doi.org/10.1023/A:1013985911759

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