Remodeling the Blood Coagulation Cascade
- Maureane Hoffman
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The concept of a coagulation cascade describes the biochemical interactions of the coagulation factors, but has flaws as a model of the hemostatic process in vivo. For example, the model cannot explain why hemophiliacs bleed when they have an intact factor VIIa/tissue factor (“extrinsic”) pathway. Hemostasis requires the formation of an impermeable platelet and fibrin plug at the site of vessel injury, but it also requires that the powerful procoagulant substances activated in this process remain localized to the site of injury. This control of blood coagulation is accomplished by localizing the procoagulant reactions to events on specific cell surfaces to keep coagulation from spreading throughout the vascular system. A consideration of the critical role of cells allows us to construct a model of coagulation that better explains bleeding and thrombosis in vivo. This cell-based model suggests that the “intrinsic” and “extrinsic” pathways are in fact not redundant systems, but operate in parallel on different cell surfaces.
- MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biological amplifier.Nature 1964;202:498-499.
- Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964;145:1310-1312.
- Hoffman M, Monroe DM, Roberts HR. The interaction of monocytes and platelets in a cell-based model of factor IX deficiency. Circulation 1992;86:I-408.
- Hoffman M, Monroe DM, Roberts HR. Cellular interactions in hemostasis. Haemostasis 1996;26(Suppl1):12-16.
- Kjalke M, Monroe D, Hoffman M, Oliver J, Ezban M, Hedner U. The effects of activated Factor VII in a cell-based model for tissue factor-initiated coagulation. Blood Coagulation Fibrinolysis 1998;9(Suppl1):S21-S25.
- Kjalke M, Monroe D, Hoffman M, Oliver J, Ezban M. Active site-inactivated Factors VIIa, Xa, and IXa inhibit individual steps in a cell-based model of tissue factor-initiated coagulation. Thrombosis Haemostasis 1998;80:578-584.
- Allen GA, Monroe DM 3rd, Roberts HR, Hoffman M. The effect of factor X level on thrombin generation and the procoagulant effect of activated factor VII in a cell-based model of coagulation [In Process Citation]. Coagul Fibrinolysis 2000;11(Suppl1):S3-S7.
- Monroe DM, Hoffman M, Roberts HR. Transmission of a procoagulant signal from tissue factor-bearing cell to platelets. Blood Coagul Fibrinolysis 1996;74:459-464.
- Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost 2001;85:958-965.
- Monkovic DD, Tracy PB. Activation of human factor V by factor Xa and thrombin. Biochemistry 1990;29:1118-1128.
- Allen DH, Tracy PB. Human coagulation factor V is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface. J Biol Chem 1995;270:1408-1415.
- Le DT, Borgs P, Toneff T, Witte M, Rapaport SI. Hemostatic factors in rabbit limb lymph: Relationship to mechanisms regulating extravascular coagulation. Am J Physiol 1998;274:H769-H776.
- Bauer KA, Kass BL, Ten Cate H, Bednarek MA, Hawiger JJ, Rosenberg RD. Detection of factor X activation in humans.Blood 1989;74:2007-2015.
- Bauer KA, Kass BL, Ten Cate H, Hawiger JJ, Rosenberg RD. Factor IX is activated in vivo by the tissue factor mechanism.Blood 1990;76:731-736.
- Jesty J, Beltrami E, Willems G. Mathematical analysis of a proteolytic positive-feedback loop: Dependence of lag time and enzyme yields on the initial conditions and kinetic parameters.Biochemistry 1993;32:6266-6274.
- Oliver JA, Monroe DM, Roberts HR, Hoffman M. Thrombin activates factor XI on activated platelets in the absence of factor XII. Arterioscler Thromb Vasc Biol 1999;19:170-177.
- Oliver JA, Monroe DM, Roberts HR, Church FC, Hoffman M. Activated protein C cleaves factor Va more efficiently on endothelium than on platelets. Blood 2002;100:539-546.
- Remodeling the Blood Coagulation Cascade
Journal of Thrombosis and Thrombolysis
Volume 16, Issue 1-2 , pp 17-20
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- coagulation cascade
- tissue factor
- Industry Sectors
- Maureane Hoffman (1)
- Author Affiliations
- 1. Department of Pathology, Duke University Medical Center and Durham VA Medical Center, Durham, NC, 27705, USA