Haemostasis

Haemostasis

Also known as: hemostasis, vascular spasm, platelet plug, primary haemostasis, secondary haemostasis, blood clotting

Haemostasis is the rapid, local arrest of bleeding from an injured vessel. It works in three overlapping steps: vascular spasm, formation of a platelet plug (primary haemostasis) and formation of a fibrin clot by coagulation (secondary haemostasis). Controlled fibrinolysis then removes the clot.

Overview

1. Vascular spasm. Injured smooth muscle contracts immediately, helped by local reflexes and by endothelin, thromboxane A₂ and serotonin released at the site. This reduces blood loss for seconds to minutes.

2. Primary haemostasis (the platelet plug). Damage to the endothelium exposes collagen beneath it. Von Willebrand factor links this collagen to platelet GPIb, which is especially important where blood flows fast, as in arteries. The bound platelets become activated. They change shape, release ADP and thromboxane A₂ to recruit more platelets, and their GPIIb/IIIa receptors change shape so they can bind fibrinogen. Fibrinogen bridges join the platelets into a loose plug within minutes.

3. Secondary haemostasis (coagulation). Tissue factor exposed at the wound starts the clotting cascade, which produces a burst of thrombin on the surface of activated platelets. Thrombin converts fibrinogen into fibrin, and factor XIIIa cross-links the fibrin. The resulting mesh traps red cells and stabilises the plug as a firm clot. Platelet actomyosin then contracts and pulls the clot tight (clot retraction).

4. Resolution. As the vessel heals, fibrinolysis removes the clot. Tissue plasminogen activator (tPA) converts plasminogen into plasmin, which breaks down fibrin and releases fragments such as D-dimer.

Keeping clotting local. Clotting is confined to the injury by natural anticoagulants and the healthy endothelium nearby: antithrombin, the protein C and protein S system, tissue factor pathway inhibitor, prostacyclin and nitric oxide.

Parts & subdivisions

Vascular spasm

Immediate vasoconstriction at the site of injury.

Platelet plug

Adhesion through von Willebrand factor and GPIb, then activation, then aggregation through fibrinogen and GPIIb/IIIa.

Coagulation

A cascade of clotting factors that generates thrombin and fibrin.

Clot retraction and repair

Platelet contraction pulls the clot tight, and PDGF stimulates repair of the vessel.

Fibrinolysis

Plasmin breaks down fibrin once the vessel has healed.

Function

Stops bleeding quickly while keeping the rest of the circulation fluid.

Provides a temporary scaffold for vessel repair.

Physiology

Each stage has its own laboratory tests. The platelet count and platelet function tests (PFA-100) assess primary haemostasis. The prothrombin time (PT/INR) assesses the extrinsic and common pathways. The activated partial thromboplastin time (aPTT) assesses the intrinsic and common pathways. Fibrinogen, the thrombin time and D-dimer assess the final stages and fibrinolysis.

Clinical significance

Disseminated intravascular coagulation (DIC)

In DIC, clotting is activated throughout the body by sepsis, trauma, cancer or obstetric emergencies. Platelets and clotting factors are used up faster than they can be replaced. The patient both forms clots in small vessels and bleeds. Tests show low platelets, a prolonged PT and aPTT, low fibrinogen and high D-dimer.

Vitamin K deficiency in newborns

Newborns have little vitamin K, so they can bleed from vitamin K deficiency (haemorrhagic disease of the newborn). This is prevented by giving vitamin K at birth.