Haematology Lecture 5: Haemostasis

Damage to the endothelium exposes platelets to subendothelial collagen, triggering platelet aggregation.

vWF, produced by endothelial cells and platelets, acts as a bridge between platelets and collagen.

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

Upon contact with damaged endothelium, platelets swell, extend pseudopodia, and release ADP, serotonin, and thromboxane A2.

Activated platelets expose fibrinogen receptors, allowing fibrinogen to act as a bridge between them, forming the platelet plug.

Blood clotting involves: 1. Vasoconstriction, 2. Platelet plug formation, 3. Fibrin network formation (coagulation), and 4. Clot retraction and dissolution.

Fibrin network formation aims to create a mesh that traps and stabilizes the blood clot.

The process of fibrin network formation includes: 1. Formation of prothrombinase (prothrombin activator) through intrinsic and extrinsic pathways. 2. Conversion of prothrombin to thrombin. 3. Thrombin catalyses the formation of the fibrin mesh from fibrinogen.

Initiated by tissue damage, exposing Tissue Factor (Factor III) which activates Factor VII. This pathway is faster than the intrinsic pathway and involves fewer steps.

Triggered by exposure of blood to collagen or foreign surfaces. This pathway starts with the activation of Factor XII and involves a cascade of enzyme activations, including factors XI, IX, and VIII.

A complex formed by activated Factor X and Factor V, along with Calcium ions (Ca2+) and platelet factor 3 (PF3). This complex is crucial for converting prothrombin to thrombin.

An enzyme formed from prothrombin by the prothrombinase complex. Thrombin plays a vital role in fibrin formation by converting fibrinogen into fibrin monomers.

A protein subunit formed from fibrinogen by the action of thrombin. These monomers polymerize to form long fibrin fibers, the building blocks of the blood clot.

An enzyme that cross-links fibrin fibers, increasing the strength and stability of the clot. It is activated by thrombin.

A vital nutrient required for the synthesis of several clotting factors, including Factors II, VII, IX, and X. Vitamin K deficiency can lead to bleeding disorders.

A process where the product of a reaction accelerates the reaction itself. In blood clotting, thrombin activates Factor V, accelerating the prothrombinase complex, leading to more thrombin production.

Calcium is required for the activation of certain clotting factors. These factors, once activated, can then bind to calcium, which is essential for the clotting process.

Clot retraction is the process where platelets contract, pulling fibrin strands together and tightening the clot. This squeezes out excess fluid (serum) and helps to stabilize the clot.

Fibrinolysis is the breakdown of a blood clot. It involves the conversion of plasminogen to plasmin, an enzyme that dissolves fibrin threads.

Antithrombin III inhibits thrombin and other clotting factors, preventing excessive clotting. Its activity is enhanced by heparin, a substance released by endothelial cells.

The Protein C pathway is an anticoagulant mechanism. Thrombomodulin on endothelial cells alters thrombin's activity, causing it to activate Protein C instead of clotting factors. Activated Protein C, with Protein S as its cofactor, then inactivates clotting factors V and VIII, reducing clotting.

TFPI is attached to the endothelium and inhibits the clotting cascade by blocking the activity of Factor X and the Factor VII/Factor III complex.

Thrombocytopenia is a condition where the number of platelets in the blood is low. This leads to easy bruising and bleeding.

Hemophilia is an inherited bleeding disorder caused by a deficiency of clotting factors VIII or IX. It is an X-linked recessive disease, affecting primarily males.

Haemostasis is the process of stopping bleeding, balancing blood fluidity and preventing excessive clotting.

The endothelium, lining blood vessels, maintains blood flow by releasing vasodilators (prostacyclin, nitric oxide) and inhibiting platelet activation. When damaged, it triggers vasoconstriction and exposes collagen, initiating clotting.

Vasoconstriction, the narrowing of the blood vessel, reduces blood flow to the injured area, slowing bleeding. This is caused by smooth muscle contraction triggered by injury or chemical signals like endothelin-1.

Platelets, when activated by damaged endothelium, adhere to exposed collagen, change shape, release signaling molecules, and aggregate to form a plug, temporarily sealing the wound.

Fibrin is a protein that forms long fibers, creating a mesh-like structure that traps blood cells and strengthens the clot.

Platelets, through the action of actin and myosin, contract, pulling on fibrin strands and tightening the clot. This strengthens the clot and squeezes out excess fluid.