The normal hemostatic response (interruption or arrest of bleeding) requires the interaction of the vessel wall, the endothelium (cells lining blood vessels), the blood platelets (rounded structures in the blood), and the coagulation cascade in order to generate thrombin. Thrombin is an enzyme that converts fibrinogen, the precursor of fibrin, to the protein fibrin, which forms the essential cohesive portion of the blood clot. The following are normal hemostatic mechanisms.

Vasoconstriction. When vessels undergo vasoconstriction (rapid closure of the vessel lumen by muscles in the vessel wall), heart rate increases and blood vessels constrict. The endothelium and the blood clot that begins to form when a vessel is injured generate several factors that lead to smooth muscle contraction in the vessel wall.

Endothelial response. The endothelium generates molecules that both prevent thrombosis (formation of a blood clot) and form platelet plugs or clots after a vessel injury.

Platelets. When a blood vessel is injured, platelets rush to form a plug at the site of injury. The plug is stabilized when fibrin is formed and crosslinked in the platelet mass.

Coagulation cascades. A series of three steps (thus cascade)—both intrinsic and extrinsic—culminate in fibrin clot formation (Figure 1).

Figure 1
  1. Thrombin splits fibrinogen into fibrin monomers (single molecules) and into the enzymes, fibrinopeptides A and P.

  2. Simple molecules (monomers) of fibrin are polymerized (formed into a compound) into fibrin strands.

  3. Coagulation factor XIII and calcium ions act together to crosslink the fibrin strands, thus forming fibrin.

Figure 1. Fibrin formation: 1, splitting of fibrinogen by thrombin; 2, polymerization (compound formation) of simple of fibrin monomers; 3, crosslinking of fibrin strands.
(From Gloviczki P, Yao, JST, eds: Handbook of Venous Disorders, 2nd ed. London: Arnold, 2001:86, Fig. 8.2.)