Hemostasis Overview

Hemostasis

• Hemostasis involves three phases: vascular, platelet, and coagulation.
• The coagulation cascade has three pathways: common, extrinsic, and intrinsic.
• Anticoagulants influence coagulation by either increasing plasmin production, blocking thrombin action, or inhibiting clotting factor synthesis.
• Clotting factors' levels impact the coagulation pathways.
• Platelets are cell fragments that are crucial for blood clotting. Their half-life is 10 days, and thrombopoietin regulates their numbers.
• Megakaryocytes are large cells with multiple DNA copies; platelets are derived from their cytoplasm.
• Platelet activation is triggered by exposed collagen, leading to aggregation and formation of a plug.
• Platelet activation also involves releasing factors to attract more platelets.
• Vasoconstriction (narrowing of blood vessels) is part of the vascular phase of hemostasis, and can be stimulated by serotonin, endothelin-1, and thromboxane A2.
• Prostacyclin and nitric oxide produced by intact endothelium prevent platelet adhesion.
• The coagulation cascade aims to form a fibrin clot to halt bleeding.
• The common pathway receives input from both extrinsic and intrinsic pathways.
• The extrinsic pathway is activated by tissue factor exposure.
• The intrinsic pathway is activated by collagen or other activators.
• Importantly, the newer cell-based model of coagulation is a more accurate representation of coagulation than the older three-pathway model.
• The cell-based theory describes three phases of coagulation: initiation, amplification, and propagation.

Hematopoiesis

• Hematopoiesis is the process of blood cell formation.
• Note the diagram showing the development of various blood cells from bone marrow, including erythrocytes, platelets, neutrophils, monocytes, basophils, eosinophils, and lymphocytes.

Platelets

• Platelets are needed for blood clotting.
• Their half-life is 10 days.
• Thrombopoietin increases platelet numbers, and megakaryocytes are the source of platelets.

Three Phases of Hemostasis

• Vascular phase: Vasoconstriction, primarily neurogenic and myogenic, is initiated by blood vessel injury. This phase is prolonged by serotonin, endothelin-1, and thromboxane A2.
• Platelet phase: This phase involves platelet activation, adherence, aggregation, and formation of a temporary hemostatic plug. Important factors are von Willebrand factor, ADP, PAF, serotonin, and thromboxane A2.
• Coagulation phase: The coagulation cascade culminates in the formation of a stable fibrin clot through a complex series of enzymatic reactions involving various clotting factors.

Coagulation Cascade Details

• Key players in the common pathway include factors X, V, II (thrombin), and XIII. These factors interact to form a cross-linked fibrin polymer that reinforces the platelet plug and stops blood loss.
• In the extrinsic pathway, tissue factor (TF) plays a central role, initiating a sequence of reactions leading to the activation of factor X and ultimately thrombin generation.
• In the intrinsic pathway, the activation of factor XII initiates a series of reactions, finally culminating in factor X activation and thrombin generation.

Removal of Clot

• After healing, the clot is removed by fibrinolysis. Plasminogen is activated to plasmin, which breaks down the fibrin polymer into fragments. tPA (tissue plasminogen activator) is released slowly by damaged endothelium to initiate this process.

Physiological Anticoagulants

• Physiological anticoagulants regulate blood clotting and prevent excessive clot formation. These include plasminogen/plasmin, tissue plasminogen activator (tPA), antithrombin III, and prostacyclin.

Cell-Based Theory of Coagulation

• This newer model emphasizes the role of cells (especially platelets and endothelial cells) in orchestrating the coagulation cascade. Critically, the initiation, amplification, and propagation phases occur on cell surfaces.

Summary

• Coagulation is a tightly regulated process involving multiple factors and steps with roles of different cells.