Secondary Hemostasis

Secondary hemostasis involves a series of blood protein reactions through a cascade-like process that concludes with the formation of an insoluble fibrin clot. This system involves multiple enzymes and several cofactors as well as inhibitors to keep the system in balance. Coagulation factors are produced in the liver, except for factor VIII, which is believed to be produced in the endothelial cells. When the factors are in a precursor form, the enzyme or zymogen is converted to an active enzyme or a protease.

The initiation of clotting begins with the activation of two enzymatic pathways that will ultimately lead to fibrin formation: the intrinsic and extrinsic pathways. Both pathways are necessary for fibrin formation, but their activating factors are different. Intrinsic activation occurs by trauma within the vascular system, such as exposed endothelium. This system is slower and yet more important versus the extrinsic pathway, which is initiated by an external trauma, such as a clot and occurs quickly

Classification of Coagulation Factors

Coagulation factors may be categorized into substrates, cofactors, and enzymes. Substrates are the substance upon which enzymes act. Fibrinogen is the main substrate. Cofactors accelerate the activities of the enzymes that are involved in the cascade. Cofactors include tissue factor, factor V, factor VIII, and Fitzgerald factor. All of the enzymes are serine proteases except factor XIII, which is a transaminase.13

There are three groups in which coagulation factors can be classified:

1. The fibrinogen group consists of factors I, V VIII, and XIII. They are consumed during coagulation. Factors V and VIII are labile and will increase during pregnancy and inflammation.

2. The prothrombin group: Factors II, VII, IX, and X all are dependent on vitamin K during their synthesis. This group is stable and remains preserved in stored plasma.

3. The contact group: Factor XI, factor XII, prekallikrein, and high-molecular-weight kininogen (HMWK) are involved in the intrinsic pathway, moderately stable, and not consumed during coagulation.5

The coagulation factors and their actions are listed in (Table 15.2).

Factor I, Fibrinogen

Substrate for thrombin and precursor of fibrin, it is a large globulin protein. Its function is to be converted into an insoluble protein and then back to soluble components. When exposed to thrombin, two peptides split from the fibrinogen molecule, leaving a fibrin monomer to form a polymerized clot.

Factor II, Prothrombin

Precursor to thrombin, in the presence of Ca2+, it is converted to thrombin (IIa), which in turn stimulates platelet aggregation and activates cofactors protein C and factor XIII. This is a vitamin K-dependent factor.

Factor III, Thromboplastin

Tissue factor activates factor VII when blood is exposed to tissue fluids.

Factor IV, Ionized Calcium

This active form of calcium is needed for the activation of thromboplastin and for conversion of prothrombin to thrombin.

Factor V, Proaccelerin or Labile Factor

This is consumed during clotting and accelerates the transformation of prothrombin to thrombin. A vitamin K-dependent factor, 20% of factor V is found on platelets.


15.2 O Factor Facts

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