Hemostasis is defined as “the termination of a bleed by mechanical or chemical means or by the complex coagulation [clotting] process of the body…”6 Composing of a coordinated sequence of events, hemostasis consists of vasoconstriction of the blood vessel, platelet adhesion and aggregation, and thrombin and fibrin synthesis (Diagram 1). The general sequence of events in hemostasis is briefly presented by describing the three main phases: vascular, platelet and coagulation phases.
Vascular phase: Immediately, when blood vessels are injured, vasoconstriction of the arteries and veins begins. Within the injured vessel wall, exposure of subendothelial tissues, collagen, and basement membrane contribute to prothrombotic activites. Clotting activities include platelet aggregation and adhesion via release of adenosine diphosphate (ADP) and von Willebrand factor (vWF).
Additionally, the release of a tissue factor (formerly known as tissue thromboplastin) during this phase initiates coagulation via the extrinsic pathway.1,2,5 At this point, the initial layer of the platelet plug is established at the site of the injury.
Platelet phase: “Platelets are cellular fragments from the cytoplasm of megakaryocytes” that survive in the vascular system for 8–12 days. They are essential for the clotting process in the blood. Primary hemostatic functions of platelets include: maintaining the health of the inner lining of the vascular wall; formation of a platelet plug during vessel wall injury; and initiation of the coagulation phase, which leads to the stabilization of the platelet plug.2
During the platelet phase, platelets become sticky and adhere to one another and to the site of injury after contact with exposed collagen and subendothelial tissue component vWF glycoprotein Ib. Additionally, Adenosine Di-phosphate (ADP) is released by exposed subendothelial tissues that cause platelets to aggregate, change shape, release dense and a-granule contents and synthesize thromboxane A2 that can further act as a feedback activator potentiating platelet responses by binding to thromboxane receptor (TP). A product of platelets, thromboxane, causes another surge of platelet aggregation.2
In summary, platelets adhere to the damaged subepithelial surface, change shape, become sticky, and aggregate to form a hemostatic platelet plug at the injured blood vessel site. Under these normal conditions, adequate numbers and function of platelets are required, resulting in the primary cessation of the bleed by the hemostatic platelet plug formation.1,2,5
Coagulation phase: Virtually simultaneously with the vascular and platelet phases, the extrinsic, intrinsic and common pathways, containing 12 circulating plasma proteins, (also termed plasma coagulation factors) are initiated (Table 1). These plasma proteins are produced in the liver. More specifically, of the 12 plasma proteins, factors II, VII, IX and X are Vitamin-K dependent for synthesis. The coagulation factors (F) are activated in a cascade-like manner within their respective pathways. The “faster” extrinsic pathway is initiated by F-VII when exposed to a tissue factor (or a membrane protein) within the injured vessel; and the intrinsic pathway is initiated when F-XII contacts with injury-exposed subendothelial tissues. Subsequently, coagulation factors in the intrinsic pathway activate one another: F-XII activates F-XI; F-XI activates-IX; and F-IX activates F-VIII. Both pathways merge and F-X is activated, yielding the activation of the common pathway. Subsequently, prothrombin is converted to thrombin; thrombin acts as a catalyst for the conversion of fibrinogen; fibrinogen is the precursor to fibrin.
|List of 12 Circulating Coagulation Factors||Intrinsic Pathway||Extrinsic Pathway||Common Pathway|
|Factor III||Tissue Factor||P|
|Factor VIII||Antihemophilic factor||P|
|Factor IX||Plasma thromboplastin||P|
|Factor X||Stuart-Power factor||P|
|Factor XI||Plasma thromboplastin antecedent||P|
|Factor XII||Hageman factor||P|
|Factor XIII||Fibrin-stabilizer factor||P|
Fibrin is thus converted to a stringy, insoluble protein that forms an intricate network of minute delicate structures called fibrils. At this point, blood cells and plasma are enmeshed in the network of fibrils to form the clot. Therefore, fibrils are responsible for tightly binding the platelet plug, stabilizing the plug, and affixing it to the site of injury. Resulting in a semi-solid, gelatinous mass, it is termed the hemostatic clot or thrombus. This definitive clot prevents blood from leaking out of blood vessels after injury. Within approximately 9 to 18 minutes, the fibrin clot is produced (Diagram 2). Under these physiological conditions, it is important to note that too few platelets, abnormal platelets, platelets that do not function normally, or deficiencies of clotting factors may not form normal clots; thus, disorders of the hemostatic system can result.1,2,5
Finally, anticlotting mechanisms (broadly termed fibrin degradation products) in the fibrinolynic pathway are activated to prevent the formation of more clots and to allow for the dissolution of the definitive clot.4,5 The expected outcome is accomplished: repair of the injured blood vessel wall results and bleeding ceases.