Question

identify factors that oppose blood clotting

Answer 1

Clotting is a homeostatic mechanism by which bleeding ceases to protect the body from excessive blood loss. The normal mechanism of clotting includes three basic steps: vascular spasm, the formation of a platelet plug, and coagulation. Coagulation is a cascade of reaction which results in the formation of a fibrin meshwork which traps more platelets and RBC’s forming a clot. There are two mechanisms involved in the activation of coagulation: intrinsic and extrinsic pathways and later both of them follow a common pathway for completion of the process. Coagulation factors are required for all these three pathways intrinsic, extrinsic and common pathways. Coagulation factors are numbered in the order of their discovery, there are 13 numbers but factors are only 12. Factor VI was subsequently found to be part of another factor.

Any factor which does not support or allows these mechanisms to work will oppose coagulation.

Factors which oppose clotting are:

· A perfectly smooth surface of the normal endothelial lining of the blood.

· Some factors promote coagulation called procoagulants. There is also another group of substances that inhibit coagulation called anticoagulants. Whether clotting will happen or not, it depends on the balance between these two groups of substances. Under normal physiological conditions there is a delicate balance between the procoagulant and anticoagulant reactions, anticoagulants predominate and prevent clotting.

This balance differs from person to person, and many factors can upset the balance.

· Because the natural anticoagulants are required to help stop the clotting process, deficiencies of one of these substances can upset this balance and prevent or delay clotting.

The most important natural anticoagulants are protein C, protein S, and antithrombin, plasmin and prostacyclin. C system is a cluster of proteins that inactivates the clotting factors involved in the intrinsic pathway. TFPI (tissue factor pathway inhibitor) inhibits the conversion of the inactive factor VII to the active form in the extrinsic pathway. Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway. Basophils release heparin, a short-acting anticoagulant that also opposes prothrombin. Heparin is also found on the surfaces of cells lining the blood vessels.

· When there is a deficiency in one or more of the natural anticoagulants the balance is tipped in the direction of clotting and individuals with these deficiencies have an increased propensity to form abnormal blood clots.

· Low levels of the natural anticoagulants or natural anticoagulants that do not work properly can occur in many conditions either inherited or acquired.

Inherited deficiencies of the natural coagulants are uncommon. Protein C deficiency occurs in 1 of every 200 to 500 people, whereas protein S deficiency can be expected in 1 of every 500 individuals. Antithrombin deficiency is the least common of the 3 deficiencies, occurring in 1 of every 2000 to 5000 people.

Acquired deficiency of anticoagulants may occur in certain situations, such as pregnancy, liver disease, severe infection or other illness, vitamin K deficiency, and certain medications like estrogen, heparin, and warfarin. Also, a recent blood clot may reduce blood levels of the natural anticoagulants.

· Same may happen if there is a deficiency of clotting factors or cofactors (vitamin K, calcium ions and phospholipids). Deficiency of coagulation factors may be inherited as in hemophilia, Von Willebrand’s disease or in some acquired occur in liver diseases as some of the coagulation factors are synthesized in the liver (II, V, VII, X, XII) and vitamin K is required for the process. Newborns (because the normal flora that produces Vitamin K in the gut is not established), administration of certain medications like broad-spectrum antibiotics which disturbs the normal gut flora, some disorders like disseminated intravascular coagulation, platelet dysfunction, etc.