The coagulation cascade consists of a complex network of reactions that are essential for the conversion of zymogens into enzymes and of inactive procofactors into cofactors. Most of these reactions take place on a membrane surface, which restricts coagulation to the site of injury. Upon initiation, these reactions serve to produce the fibrin that is necessary for the formation of a stable hemostatic plug. In addition, these reactions provide feedback loops that limit and localize thrombus formation and regulate thrombus resolution. This chapter highlights key biochemical characteristics of the individual coagulation factors, essential aspects regarding their synthesis, and the clinical importance of acquired or inherited variations that affect their quantity or function. The coagulation factors are grouped as (a) the vitamin K–dependent zymogens (prothrombin, factor VII, factor IX, factor X, and protein C), (b) the procoagulant cofactors (factor V, factor VIII), (c) the soluble cofactors (protein S, von Willebrand factor), (d) factor XI and the contact system (factor XII, prekallikrein, and high-molecular weight kininogen), (e) the cell-associated cofactors (tissue factor [TF], thrombomodulin, endothelial protein C receptor), (f) the fibrin network (fibrin[ogen], factor XIII, thrombin-activatable fibrinolysis inhibitor), and (g) inhibitors of coagulation (antithrombin, TF pathway inhibitor, protein Z/protein Z–dependent protease inhibitor). Table 112–1 summarizes the major features of the coagulation factors addressed in this chapter. The final sections of this chapter present an overview of the coagulation cascade in which the pathways of hemostasis including the contribution of endothelial cells, blood platelets, and immune cells are described.
Acronyms and Abbreviations
ADAMTS13, a disintegrin and metalloproteinase with thrombospondin motifs 13; a-HUS, atypical hemolytic uremic syndrome; APC, activated protein C; aPTT, activated partial thromboplastin time; ADP, adenosine diphosphate; AT, antithrombin; C4BP, complement 4b–binding protein; COX, cyclooxygenase; EGF, epidermal growth factor; EPCR, endothelial protein C receptor; EPCT, endothelial protein C receptor; ER, endoplasmatic reticulum; ERGIC, ER-Golgi intermediate compartment; Gla, γ-carboxyglutamic acid; GP, glycoprotein; HK, high-molecular-weight kininogen; LMAN1, mannose-binding lectin-1; NET, neutrophil extracellular trap; NO, nitric oxide; PAI-1, plasminogen activator inhibitor type 1; PAR, protease-activated receptor; PF-4, platelet factor 4; PK, prekallikrein; poly-P, polyphosphate; RVV, Russell's viper venom; SHBG, sex hormone–binding globulin; TAFI, thrombin-activatable fibrinolysis inhibitor; TFPI, tissue factor pathway inhibitor; UFH, unfractionated heparin; VWD, von Willebrand disease; VWF, von Willebrand factor; ZPI, protein Z–dependent protease inhibitor.
TABLE 112–1.Characteristics of Coagulation Proteins ||Download (.pdf) TABLE 112–1. Characteristics of Coagulation Proteins
| || ||Plasma Concentration ||Mr ||Plasma Half-Life |
| ||Protein ||(mcg/mL) ||(nmol/L) ||(kDa) ||(hours) |
| + Gla domain ||Prothrombin (factor II) ||100 ||1400 ||72 ||60 |
| ||Factor VII ||0.5 ||10 ||50 ||3–6 |
| ||Factor IX ||5 ||90 ||55 ||18–24 |
| ||Factor X ||10 ||170 ||59 ||34–40 |
| ||Protein C ||4 ||65 ||62 ||6–8 |
| – Gla domain ||Factor XI ||5 ||30 ||160 ||60–80 |
| ||Factor XII ||40 ||500 ||80 ||50–70 |
| ||Prekallikrein ||40 ||490 ||85 ||35 |
| ||Factor XIIIA*? ||– ||– ||83 ||– |
| ||Factor XIIIB* ||7 ||94 ||76.5 ||–...|