McKenna's Pharmacology for Nursing, 2e

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

DRUGS AFFECTING CLOT FORMATION AND RESOLUTION Antiplatelet agents

DRUGS USED TO CONTROL BLEEDING Antihaemophilic agents antihaemophilic factor, recombinant coagulation factor VIIa coagulation factor VIII factor IX complex Haemostatic agents absorbable gelatin aminocaproic acid aprotinin human fibrin sealant microfibrillar collagen

Anticoagulants antithrombin III apixaban bivalirudin dabigatran fondaparinux heparin rivaroxaban warfarin Thrombolytic agents

Other drugs affecting clot formation Low-molecular-weight heparins dalteparin enoxaparin tinzaparin Anticoagulant adjunctive therapy lepirudin protamine sulfate vitamin K Haemorheologic agent oxpentifylline

abciximab anagrelide aspirin cilostazol clopidogrel dipyridamole eptifibatide

prasugrel ticagrelor ticlopidine tirofiban

alteplase reteplase

streptokinase tenecteplase

T he cardiovascular system is a closed system, and blood remains in a fluid state while in it. Because the blood is trapped in a closed space, it maintains the difference in pressure required to keep the system moving along. Everything in the cardiovascular system moves from higher pressure to lower pressure. If the vascular system is injured—from a cut, a puncture or capillary destruc­ tion—the fluid blood could leak out, causing the system in that area to lose pressure and changing the flow in the system, potentially shutting it down entirely. To deal with the problem of blood leaking and potentially shutting down the system, blood that is exposed to an injury in a vessel almost immediately forms into a solid state, or clot, which plugs the hole in the system and keeps the required pressure differences intact. BLOOD COAGULATION People injure blood vessels all the time (e.g. by coughing too hard, by knocking into the corner of the desk when sitting down). Consequently, the vascular system must maintain an intricate balance between the tendency to clot or form a solid state, called coagulation , and the need to “unclot”, or reverse coagulation, to keep the vessels open and the blood flowing. If a great deal of vascular damage occurs, such as with a major cut or incision, the balance in the area shifts to a procoagu­ lation mode and a large clot is formed. At the same time, the enzymes in the plasma work to dissolve this clot before blood flow to tissues is lost, which otherwise would lead to hypoxia and potential cell death. Drugs that affect blood coagulation work at various steps in the blood clotting and clot-dissolving processes to restore the balance that is needed to maintain the car­ diovascular system. Box 48.1 discusses the uses of these drugs in various age groups.

Clotting process Blood coagulation is a complex process that involves vasoconstriction, platelet clumping or aggregation and a cascade of clotting factors produced in the liver that eventually react to break down fibrinogen (a protein also produced in the liver) into insoluble fibrin threads. When a clot is formed, plasmin (another blood protein) acts to break it down. Blood coagulation can be affected at any step in this complicated process to alter the way that blood clotting occurs. Vasoconstriction The first reaction to a blood vessel injury is local vaso­ constriction (Figure 48.1). If the injury to the blood vessel is very small, this vasoconstriction can seal off any break and allow the area to heal. Platelet aggregation Injury to a blood vessel exposes blood to the collagen and other substances under the endothelial lining of the vessel. This exposure causes platelets in the circulating blood to stick or adhere to the site of the injury. Once they stick, the platelets release adenosine diphosphate (ADP) and other chemicals that attract other platelets, causing them to gather or aggregate and to stick as well. ADP is also a precursor of the prostaglandins, from which thromboxane A 2 is formed. Thromboxane A 2 causes local vasoconstriction and further platelet aggregation and adhesion. This series of events forms a platelet plug at the site of the vessel injury. In many injuries, the com­ bination of vasoconstriction and platelet aggregation is enough to seal off the injury and keep the cardiovascu­ lar system intact (Figure 48.2). Intrinsic pathway As blood comes in contact with the exposed collagen of the injured blood vessel, one of the clotting factors,