Question

What are the factors and circumstances that make sure we do not over clot or under clot?

Answer 1

Blood clotting, or coagulation, is the process that prevents excessive bleeding when a blood vessel is injured. Platelets (a type of blood cell) and proteins in your plasma (the liquid part of blood) work together to stop the bleeding by forming a clot over the injury.

Once we get we injured, this is what happening: 1) vasoconstriction, 2) temporary blockage of a break by a platelet plug, and 3) blood coagulation, or formation of a fibrin clot. There are various clotting factors involved in this process.

• Factor I - fibrinogen
• Factor II - prothrombin
• Factor III - tissue thromboplastin (tissue factor)
• Factor IV - ( Ca++ )
• Factor V - labile factor or proaccelerin
• Factor VI - unassigned
• Factor VII - stable factor or proconvertin
• Factor VIII - antihemophilic factor
• Factor IX - plasma thromboplastin component, Christmas factor
• Factor X - Stuart-Prower factor
• Factor XI - plasma thromboplastin antecedent
• Factor XII - Hageman factor
• Factor XIII - fibrin-stabilizing factor

Clot formation - Once the platelet plug has been formed by the platelets, the clotting factors are activated in a sequence of events known as 'coagulation cascade' which leads to the formation of Fibrin from inactive fibrinogen . Thus, a Fibrin mesh is produced all around the platelet plug to hold it in place. During this process some red and white blood cells are trapped in the mesh and the resultant plug is called as 'thrombus' or 'Clot'.

Regulators of clotting

Five mechanisms keep platelet activation and the coagulation cascade in check.

Protein C

Protein C is a major physiological anticoagulant. It is activated into activated protein C (APC) by thrombin. Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades Factor Va and FactorVIIIa.

Factor Va and Factor VIIIa are formed by the activation of Factor V and FactorVIII respectively during clotting process.Inactivation of these factors checks the process of clotting.

Antithrombin

Antithrombin degrades : thrombin, Factor IXa, Factor Xa, Factor XIa, and Factor XIIa.

Factor IXa, Factor Xa, Factor XIa, and Factor XIIa are the activated forms of Factor IX, Factor X, Factor XI, and Factor XII respectively.Their activation promotes clotting and inactivation decreases clotting.

Tissue factor pathway inhibitor (TFPI)

Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of Factor VII and Factor X.

Plasmin

Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation.

Prostacyclin

Prostacyclin inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.

Fibrinolysis

Finally, blood clots are reorganised and resorbed.