Pharmacology of Blood Coagulation

Thrombolytics, also known as fibrinolytics, include recombinant tissue plasminogen activator (TPa) (i.e., alteplase, reteplase, and tenecteplase), urokinase, and streptokinase. The agents promote the breakdown of a blood clot by converting plasminogen to plasmin, which then degrades fibrin. Thrombolytics are particularly helpful for conditions related to vascular obstruction by a blood clot (e.g., acute STEMI, pulmonary embolism (PE), deep venous thrombosis (DVT), and acute ischemic stroke). Efficacy declines the longer tissue ischemia persists; therefore, timing of therapy is particularly important in myocardial infarction and stroke. Life-threatening bleeding and allergic reactions are potentially serious complications. Weighing the risks and benefits of thrombolytics and evaluating individuals for contraindications/bleeding risk before initiating therapy is important.

Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders.

Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. As a result, platelets have a diameter of 2–3 μm. Nuclei are not present; however, a variety of organelles are present and aid in different platelet functions.

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Common side effects include GI irritation, prolonged bleeding, and AKI.

Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants are used in the treatment and prevention of thrombotic and embolic diseases including cardioembolic ischemic stroke, acute coronary syndrome, and venous thromboembolism, among other conditions. Patients with atrial fibrillation or thrombophilias may require indefinite or lifelong anticoagulation. Accordingly, the route of administration, drug interactions, pharmacokinetics, and availability of reversal factors should be considered while selecting the anticoagulant therapy.

Antiplatelet agents are medications that inhibit platelet aggregation, a critical step in the formation of the initial platelet plug. Abnormal, or inappropriate, platelet aggregation is a key step in the pathophysiology of arterial ischemic events. The primary categories of antiplatelet agents include aspirin, ADP inhibitors, phosphodiesterase/adenosine uptake inhibitors, and glycoprotein IIb/IIIa inhibitors. Common indications for antiplatelet agents include the treatment and prevention of ischemic heart disease and stroke, peripheral artery disease, and other conditions associated with a high risk for arterial thrombosis.