McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 4 8 Drugs affecting blood coagulation

Hageman factor (also called factor XII), a chemical substance that is found circulating in the blood, is acti­ vated. (Clotting factors are often known by a name and by a Roman numeral. When one of these factors becomes activated, the lowercase letter “a” is added; e.g. activated Hageman factor is also called factor XIIa.) The activation of Hageman factor starts a number of reactions in the area: The clot formation process is activated, the clot-dissolving process is activated and the inflammatory response is started (see Chapter 15). The activation of Hageman factor first activates clotting factor XI (plasma thromboplastin antecedent [PTA]) and then activates a cascading series of coagulant sub­ stances called the intrinsic pathway (Figure 48.3) that ends with the conversion of prothrombin to thrombin. Activated thrombin breaks down fibrinogen to form insoluble fibrin threads, which form a clot inside the blood vessel. The clot, called a thrombus, acts to plug the injury and seal the system. Extrinsic pathway While the coagulation process is going on inside the blood vessel via the intrinsic pathway, the blood that has leaked out of the vascular system and into the surrounding tissues is caused to clot by the extrinsic pathway . Injured cells release a substance called tissue thromboplastin, which activates clotting factors in the blood and starts the clotting cascade to form a clot on the outside of the blood vessel. The injured vessel is now vasoconstricted and has a platelet plug, as well as a clot on both the inside and the outside of the blood vessel in

Injured epithelium releases factor

Platelets adhere and release granules

A

Plug formed of platelets and fibrian

B

FIGURE 48.2  A. Damaged vessel endothelium is a stimulus to circulating platelets, causing platelet adhesion. B. Platelets release mediators, and platelet aggregation results.

Blood vessel injury

Tissue injury

Exposure of blood to subendothelial collagen, etc.

Release of tissue thromboplastin

Vitamin K

Hageman factor (XII)

XII a

Factor VII

VII a

Liver cells

Warfarin

PTA (XI)

XI a

Ca 2+

Vitamin K

IX a

Christmas factor (IX)

Liver cells

Ca 2+

Warfarin

Intrinsic pathway

Extrinsic pathway

Factor VIII Ca 2+ Phospholipids

Vitamin K

X a

Liver cells

Stuart factor (X)

Warfarin

Ca 2+ Phospholipids Factor V

Antithrombin

Vitamin K

Heparin

Liver cells

Prothrombin (II)

Thrombin

Factor XIII a

Warfarin

FIGURE 48.3  Details of the intrinsic and extrinsic clotting pathways. The sites of action of some of the drugs that can influence these processes are shown in red.

Fibrin (soluble)

Clot (insoluble)

Fibrinogen (I)