Overview
Hemostasis stops bleeding through the vessel wall, platelets and plasma coagulation factors, and it is balanced by natural anticoagulants and fibrinolysis.
Hemostasis is the set of mechanisms that stops bleeding from an injured vessel while keeping blood fluid elsewhere. This topic covers the vascular reaction, the formation of the platelet plug (primary hemostasis), the plasma coagulation factors and the cascade that produces a stable fibrin clot (secondary hemostasis), clot retraction, and the basic laboratory tests. Fibrinolysis and the natural anticoagulants are covered in the later sections.
Stages of hemostasis and platelets
Hemostasis runs as overlapping stages rather than strictly one after another:
- Vascular spasm: immediate local vasoconstriction.
- Platelet plug formation: adhesion, activation and aggregation of platelets.
- Blood coagulation: conversion of soluble fibrinogen to an insoluble fibrin network.
- Clot retraction, followed by fibrinolysis and tissue repair.
Vasoconstriction results from direct myogenic response of the injured smooth muscle, local axon reflexes, and vasoactive substances released by platelets and endothelium, especially thromboxane A₂, serotonin and endothelin. It is most effective in small vessels. Intact endothelium normally prevents clotting by producing prostacyclin (PGI₂) and nitric oxide, which inhibit platelets; injury exposes subendothelial collagen and tissue factor, which trigger hemostasis.
Platelets (thrombocytes) are anucleate fragments of bone marrow megakaryocytes, produced under the control of thrombopoietin (made mainly in the liver). Normal count is about 150–400 × 10⁹/L and lifespan about 7–10 days; old platelets are removed mainly by the spleen. They contain an open canalicular system, contractile proteins (actin, myosin, thrombosthenin) and two main granule types:
- Dense granules: ADP, ATP, serotonin, Ca²⁺.
- α-granules: fibrinogen, von Willebrand factor, factor V, PDGF, platelet factor 4.
Formation of the platelet plug proceeds in three steps:
- Adhesion: von Willebrand factor (vWF) bridges exposed collagen to the platelet receptor GPIb-IX-V; platelets also bind collagen directly via GPVI and integrin α2β1 (GPIa/IIa).
- Activation: shape change with pseudopodia, granule release, and synthesis of thromboxane A₂ from arachidonic acid via cyclooxygenase-1 (irreversibly blocked by aspirin). Negatively charged phospholipids (phosphatidylserine) are exposed on the surface and serve as the site for coagulation reactions.
- Aggregation: ADP, TXA₂ and thrombin activate the integrin GPIIb/IIIa (αIIbβ3), which binds fibrinogen and links neighbouring platelets. This positive feedback builds a loose, temporary plug.