Coagulation is a complex process by which plasma proteins interact to form a stable fibrin gel.4 The fibrin strands thus formed create a meshwork that cements blood components together, a process known as syneresis. Ultimately, a blood clot is formed.5,6 Normal coagulation depends on the presence of all clotting factors and follows specific sequences known as pathways or cascades.
At least 30 substances are believed to be involved in the clotting process. The most significant ones are shown in Table 2-1. Note that clotting factors are now designated by Roman numerals. The "a" indicates an activated clotting factor.7 There is no factor VI because that number was originally assigned to what is now known to be activated factor V.8
Each of the clotting factors is involved at a specific step in the coagulation process, with one clotting factor leading to activation of the next factor in the sequence. Three major clotting sequences have been identified: (1) the intrinsic pathway, (2) the extrinsic pathway, and (3) the common final pathway.
The intrinsic pathway is activated when blood comes in contact with the injured vessel wall; the extrinsic pathway is activated when blood is exposed to damaged tissues. Both pathways are needed for normal hemostasis, and both lead to the common final pathway.9 A schematic representation of the intrinsic, extrinsic, and common pathways is shown in Figure 2-1.
The common final pathway is initiated with the activation of factor X. Factors X and V, along with platelet phospholipid and calcium, combine to form prothrombin activator, which converts prothrombin to thrombin. Thrombin subsequently converts fibrinogen to fibrin gel. Thrombin also enhances platelet release reactions, augments the activation of factors V and VIII, and activates factor XIII.10 Stable (insoluble) fibrin is formed in the presence of activated factor XIII.
Calcium plays an important role throughout the coagulation process. It is necessary for the activation of factors VII, IX, X, and XI; for the conversion of prothrombin (factor II) to thrombin; and for the formation of fibrin. However, hypocalcemia does not usually cause bleeding difficulties because cardiac arrest occurs before levels are low enough to precipitate abnormal hemostasis. Citrate, oxalate, and ethylenediaminetetra-acetic acid (EDTA) are anticoagulants because they bind calcium and prevent it from participating in the clotting process. Any one of these substances may be added to the vacuum tubes used to collect peripheral blood samples when an uncoagulated specimen is needed (see Appendix I, Table A-1).11