Haematology Lecture 5: Haemostasis

The process of stopping bleeding, maintaining the balance between preventing blood loss and keeping blood fluid.

The inner lining of blood vessels, endothelium, plays a crucial role in regulating blood flow and clotting. It helps maintain a smooth surface for blood flow and releases factors to either promote or inhibit clotting.

An intact endothelium releases factors like prostacyclin and nitric oxide, which cause vasodilation to promote smooth blood flow.

Damaged endothelium releases endothelin-1, a vasoconstrictor that narrows the vessel, reducing blood flow. This is the first step in stopping bleeding.

The process of blood clotting occurs in four stages: 1) Vasoconstriction, 2) Platelet Plug Formation, 3) Fibrin Network Formation (coagulation), 4) Clot Retraction and Dissolution.

The blood vessel itself constricts, responding to stress and stretch, in an attempt to immediately reduce blood flow.

Damaged endothelium releases endothelin-1, which causes vasoconstriction by inhibiting the release of vasodilators like nitric oxide and prostacyclin.

Platelets stick to the damaged endothelium and collagen fibers exposed by the injury.

Platelet aggregation is initiated when platelets encounter damaged endothelium and are exposed to subendothelial collagen.

Platelets can bind directly to collagen or indirectly via von Willebrand factor (vWF), a glycoprotein that acts as a bridge between platelets and collagen.

Prostacyclin and nitric oxide (NO) released from healthy endothelium inhibit platelet activation.

When platelets encounter damaged endothelium, they swell, extend pseudopodia, and release ADP, serotonin, and thromboxane A2.

Activated platelets release ADP and serotonin, which cause vasoconstriction and further activate other platelets.

Activated platelets have fibrinogen receptors. Fibrinogen acts as a bridge, connecting activated platelets to form a platelet plug.

The objective of forming a fibrin network is to create a mesh that stabilizes the platelet plug and strengthens the clot.

The fibrin network forms through three steps: 1) Formation of prothrombinase (prothrombin activator), 2) Conversion of prothrombin to thrombin, and 3) Thrombin catalyzes fibrin mesh formation from fibrinogen.

Calcium is essential for the activation of certain clotting factors, enabling them to bind to other proteins involved in clot formation.

Initiated by tissue damage, exposing Tissue Factor (Factor III). This pathway involves a cascade of enzyme activation leading to the conversion of prothrombin to thrombin, ultimately forming the fibrin mesh.

Activated by exposure of blood to collagen or foreign surfaces. Involves a series of steps that begin with the activation of Factor XII and culminates in the formation of thrombin, leading to the fibrin mesh.

Cofactors, such as vitamin K, are required for the enzymatic modification of clotting factors, which allows them to bind calcium and contribute to clot formation.

After a clot forms, platelets contract, pulling fibrin strands together and squeezing out serum. This process compresses the clot and helps to seal the blood vessel.

A protein exposed during tissue damage that initiates the extrinsic pathway of blood clotting. It activates Factor VII, starting the cascade of events.

A complex formed by activated Factor X and Factor V, responsible for converting prothrombin to thrombin. Critical for the final steps of blood clotting.

The process by which a blood clot is broken down. It involves the conversion of plasminogen to plasmin, which digests fibrin threads and other clotting factors.

An enzyme generated by the prothrombinase complex. It acts on fibrinogen to form fibrin, the main component of the clot. Thrombin also amplifies the clotting process through positive feedback.

Antithrombin III is a protein that prevents excessive blood clotting by inhibiting thrombin and other clotting factors. Its action can be enhanced by heparin.

A network of sticky protein fibers formed from fibrinogen, which traps blood cells, platelets, and other molecules to form a stable clot. It prevents further blood loss.

This pathway involves Thrombomodulin, which alters the activity of thrombin, leading to the activation of Protein C. Protein C, with its cofactor Protein S, then inactivates factors V and VIII, helping to control clotting.

TFPI is a protein attached to endothelium that blocks the activation of Factor X and the Factor VII/Factor III complex, inhibiting blood clot formation.

An essential vitamin required for the production of several clotting factors, including Factors II, VII, IX, and X. It plays a crucial role in the blood clotting process.

A protein responsible for stabilizing the fibrin mesh by cross-linking fibrin fibers. Activated by thrombin, it helps strengthen and solidify the clot to prevent premature breakdown.

A genetic disorder characterized by the absence or deficiency of clotting factors VIII or IX, leading to excessive bleeding.