Normal hemostasis


Hemostasis has three stages: platelet plug formation (primary hemostasis), platelet plug stabilization with cross-linked fibrin (secondary hemostasis), and clot breakdown (fibrinolysis).

Hemostasis has three stages: platelet plug formation (primary hemostasis), platelet plug stabilization with cross-linked fibrin (secondary hemostasis), and clot breakdown (fibrinolysis).

Primary hemostasis

Under normal conditions, platelets adhere to damaged subendothelium through the interaction of various ligands and receptors. After platelets adhere, they change shape to facilitate cross-bridging, which leads to platelet activation. Platelet activation involves the release and synthesis of agonists (adenosine diphosphate, serotonin, epinephrine, platelet-activating factor, and thromboxane A2) from the platelets, which recruit additional platelets and promote further adhesion and activation.1

Platelet activation can also occur independently of aggregation in the presence of thrombin. Thrombin is a potent platelet activator, and inflammation may trigger thrombin production and circulation and lead to widespread platelet activation.2 The activated platelet membranes provide a framework for the assembly of coagulation factors and catalyze fibrinogen's conversion to fibrin.1

Secondary hemostasis

Secondary hemostasis results in stable thrombus formation by cross-linking fibrin and consists of three phases: initiation, amplification, and propagation (see Figure).

An overview of a cell-based model of coagulation. Damage to the endothelium exposes tissue factor (TF) to circulating active VIIa, which initiates coagulation. The TF-VIIa complex activates IX, X, and additional VII. Xa can activate V. Va then joins with its cofactor (factor Xa) and activates small amounts of prothrombin (II) to thrombin (IIa). The thrombin then diffuses to activate platelets, cleave vWF from VIII, and activate XI and V. VIIIa binds to IXa and activates Xa. Xa then binds to Va to cleave prothrombin to thrombin. Thrombin cleaves fibrinogen to fibrin, and factor XIII (not shown) cross-links the fibrin strands to form a stable thrombus.

Initiation involves the exposure of tissue factor to blood after endothelial damage. Circulating activated factor VII then binds to tissue factor, leading to activation of the common pathway and a small amount of thrombin production. The small amount of thrombin produced by this reaction is then free to activate platelets as well as start the amplification phase.

The amplification phase involves cleavage of von Willebrand factor from factor VIII and activation of factors VIII, V, and IX, eventually leading to an explosion of thrombin formation.

Key: Coagulation Factors

In the propagation phase, fibrinogen is cleaved into fibrin, which is further cross-linked by factor XIII, resulting in stable thrombus formation.2 Many of these processes occur on the activated platelet surface.


The final component of normal hemostasis is dissolution of the fibrin mesh, or fibrinolysis. Plasmin breaks down the fibrin clot. Plasmin forms when plasminogen is cleaved by plasminogen activators including tissue plasminogen activator and urokinase. The endothelial cells release tissue plasminogen activator in response to injury and in response to thrombin. Urokinase seems to play a more important role in extravascular fibrinolysis.

The main inhibitors of fibrinolysis are plasminogen activator inhibitor-1, which blocks the effects of tissue plasminogen activator that result in fibrinolysis, and thrombin-activatable fibrinolysis inhibitor, which blocks the conversion of plasminogen to plasmin.3


1. McMichael M. Primary hemostasis. J Vet Emerg Crit Care 2005;15(1):1-8.

2. Smith SA. The cell-based model of coagulation. J Vet Emerg Crit Care 2009;19(1):3-10.

3. Hopper K, Bateman S. An updated view of hemostasis: mechanisms of hemostatic dysfunction associated with sepsis. J Vet Emerg Crit Care 2005;15(2):83-91.

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