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VetBooks.ir                XII  XI      Ca                               TF


                            Intrinsic   IX     Ca                 VII     Extrinsic
                            pathway                                       pathway
                                              VIII

                                                   X
                                                        Ca
                                                   V
                                      Common
                                      pathway
                                                   II
                                                        XIII   Crosslinked
                                                   I
                                                                fibrin clot
            Fig. 9.1.  Traditional (‘waterfall’) model of secondary hemostasis. The extrinsic ‘arm’ of the coagulation cascade begins
            with exposed tissue factor (TF or factor III) that cleaves factor VII to factor VIIa (activated factor VII). The activated factor
            VII then triggers the common pathway of coagulation by cleaving factor X to Xa that, in the presence of calcium (Ca),
            will activate factor V. Factor Va then cleaves prothrombin (factor II) to thrombin (factor IIa) which in turn causes fibrinogen
            (factor I) to activate to fibrin (factor Ia). The resulting fibrin is then crosslinked into the final ‘hard’ clot by the action of
            factor XIII. The intrinsic ‘arm’ of the coagulation cascade is also able to activate the common pathway to make fibrin and
            a crosslinked clot. The intrinsic arm classically begins with factor XII becoming activated to XIIa which then cleaves factor
            XI to XIa in the presence of Ca. The activated factor XI will stimulate conversion of factor IX to IXa in the presence of Ca
            which then activates VIII to VIIIa. The activated factor VIII will subsequently trigger the common pathway.


            Table 9.1.  Summary of the most common contents of platelet granules and their most common function in coagulation.
             Platelet granules              Function

             vWF (α granules)               Platelet–platelet and platelet–endothelium binding
             Fibrinogen (α granules)        Platelet–platelet and platelet–endothelium binding
             Factor V (α granules)          Secondary hemostasis, forms part of prothrombinase complex
             Factor XIII (α granules)       Secondary hemostasis, crosslinks fibrin strands
             Antithrombin (α granules)      Inhibits secondary hemostasis, inhibits thrombin and factor X
             TFPI (α granules)              Inhibits secondary hemostasis, inhibits extrinsic factor tenase complex
             Protein S (α granules)         Inhibits secondary hemostasis, inhibits factors VIII and V
             Plasmin/plasminogen (α granules)  Initiates fibrinolysis
             Prothrombin (α granules)       Activates platelets, involved in secondary hemostasis
             Calcium (dense granules)       Important cofactor for all stages of secondary hemostasis
             ADP (dense granules)           Binds to ADP receptor on the platelet cell surface causing platelet
                                             activation
             Serotonin (dense granules)     Causes platelet aggregation, platelet activation, local blood vessel
                                             dilation
             Thromboxane A  (created in platelet)  Manufactured via the arachidonic acid cascade within the platelet
                        2
                                            Binds to the TXA  receptor on the platelet surface to activate platelets
                                                        2
            ADP, adenosine diphosphate; TFPI, tissue factor pathway inhibitor; TXA , thromboxane A2; vWF, von Willebrand factor.
                                                        2

             178                                                         E.J. Thomovsky and A.C. Brooks
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