Antiplatelets to Anticoagulants: Making Sense of the Coagulation Cocktails

Anticoagulation is the cornerstone of therapy in patients with ischemic cardiovascular disease. In patients who develop an acute coronary syndrome, following percutaneous coronary interventions, or with an acute ischemic stroke, the rupture or injury of an atherosclerotic arterial plaque serves as a nidus for platelet aggregation and thrombus formation, which, in turn, may cause myocardial infarction, stroke, or death Activation and expression of the glycoprotein IIb/IIIa receptor (where fibrinogen binds) on platelets leads platelet aggregation and, thrombus formation. When this receptor is activated, circulating fibrinogen binds to it and cross-links with adjacent platelets to create a platelet-fibrinogen matrix. Since platelets have a pivotal role in the pathogenesis of thrombosis after plaque rupture, antiplatelet agents including aspirin, thienopyridines (clopidogrel-Plavix), and the glycoprotein IIb/IIIa inhibitors, reduce adverse events that are associated with plaque rupture. Fibrinolytic agents are infrequently used in the current era with all of the available catheter and pharmacologic agents available. As a result, patients often present for surgery with underlying hemostatic disorders because of preexisting preoperative anticoagulation or antiplatelet therapy. Patients may also present receiving anticoagulation therapy for reasons that include atrial fibrillation, venous thrombosis prophylaxis, prosthetic valves, or for coronary artery disease. All therapies that prevent clot from forming in pathologic states, also interfere with normal hemostasis, an important mechanism to protect patients from exsanguination. Under normal circumstances, there is a complex and delicate equilibrium between blood cells, platelets, coagulation factors, natural inhibitors of coagulation, and the fibrinolytic system. Surgical patients also develop additional acquired hemostatic alterations that contribute to postoperative bleeding, causes that include activation of the coagulation, fibrinolytic, and inflammatory pathways. Even healthy patients can develop massive hemorrhage and/or tissue injury following trauma, surgery, or in an obstetrical population. Hemostasis is also a far more complex system than intrinsic and extrinsic hemostatic activation as taught in medical school. Multiple factors are responsible for stopping bleeding including release of tissue factor, and generation of factor VIIa, platelet activation, and the complex cellular and humoral amplification that follows. The increasing use of low-molecular weight heparins (LMWH), heparinoids (Orgaran), pentasaccharide (fondaparinux), oral anticoagulants (warfarin and new oral anti-Xa inhibitors), platelet inhibitors (thienopyridines-clopidogrel or IIb/IIIa receptor antagonists), or direct thrombin inhibitors (r-hirudin, bivalirudin, argatroban), also may potentiate bleeding. This review will focus on current pharmacologic therapies surgical patients may receive and therapeutic prohemostatic pharmacologic approaches that are used to treat or prevent bleeding.