Coagulation Tests

Description

Haemostasis is a complex process involving blood vessels, platelets and coagultion proteins. It is divided into a vascular/platelet phase (primary haemostasis) and a subsequent coagulation phase (secondary haemostasis). The end product of haemostasis is a solid clot composed of fused platelest enclosed in a mesh of fibrin strands. Excessive clot formation is prevented by the fibrinolytic system, which acts to breakdown fibrin within blood clots.

Primary haemostasis starts with vasoconstriction triggered by vessel injury, and continues until vessel integrity is restored and bleeding stops. As well as lacerations, vascular damage may result from trauma, excessive turbulense, indwelling catheters, or inflammation (endocarditis). Plates respond to vessel injusry be adhhereing to vascular subendothelium (adhesion) and to other platelets (primary aggreggation), changing shape and releaseing substances which promote vasoconstriction and activate more platelets (the relsease reaction). Platelet contraction and aaggregation triggered by the substances released by the platelets (secondary aggregation) continue until the injusty is sealed by a fragile platelet plug.

Primary haemostasis alone will only be temporarily beneficial unless the platelet plug is reinforced by fibrin assembled by the clotting cascade (secondary haemostsis). Secondary haemostasis is dependent on the interactions of a number of proteins (clotting factors) within the intrinsic, extrinsic and common pathways of the cascade. The clotting factors aer synthesisde in the liver. The factors circulate in the plasma in an inactive from. Fatos I, VII, IX and X are dependent upon vitamin K to become active.

Fibrinolysis, the process of plasmin-induced fibrin breakdown, prevents uncontrolled widespread clotting and is comprised of a number of mechanisms. The two most important naturally occuring antigcoagulant proteins are antithrombin III (ATIII) and Proteoin C. When complexed with heparin sulphate, ATIII inactivates thrombin and can also inactivate factors IX and X. Firbrin degratation products (FDP) are the end products of fribrinoloysis.

Normally, haemostastis is maintained by three key events³. Firstly, platelets are activated, adhere to endothelial connective tissue and aggregate to form a platelet plug. Next, substances are released that trigger coagulation and vasoconstriction. Finally, fibrinogen is polymerised to fibrin which reinforces the platelet plug. Some components of the coagulation and fibrin formation stages are dependent on vitamin K, and it is these which are influenced by anticoagulant rodenticide activity.

Two simultaneous cascades are activated to achieve coagulation: the intrinsic and extrinsic pathways. The intrinsic pathway is activated by contact with collagen due to blood vessel injury and involves the clotting factors XII, XI, IX and VIII. The extrinsic pathway is triggered by tissue injury and is effected via factor VII. These pathways progress independently before converging at the common pathway, which involves the factors X, V, II and I and ultimately results in the formation of fibrin from fibrinogen.

Within each of the three arms of the coagulation cascade, certain clotting factors are dependent on vitamin K for activity. These are factor VII, factor XI and factors II and X in the extrinsic, intrinsic and common pathways respectively. Vitamin K carboxylates these factors to their fuctional forms, and becomes oxidised itself in the process. Vitamin K is always required for the production of new II, VII, IX, and X in the liver and levels are tightly regulated. It is therefore essential that vitamin K is recycled after it is oxidised in the carboxylation reaction, and the enzyme vitamin K epoxide reductase is respsonsible for this.