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Flashcards in Hematology - Pharmacology Deck (116)
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What is the mechanism by which heparin anticoagulates?

It catalyzes the activation of antithrombin III and reduces levels of thrombin and factor Xa


How can you rapidly reverse the anticoagulation induced by heparin administration?

Give protamine sulfate, a positively charged molecule that binds negatively charged heparin


Compare enoxaparin and heparin.

Enoxaparin is more specific for factor Xa, has higher bioavailability, and 2-4 times longer half-life


What difference between heparin and enoxaparin should be considered when there is a concern of excessive anticoagulation?

Enoxaparin is not easily reversible, whereas heparin can be reversed by the administration of protamine sulfate; heparin also has a shorter half-life


What are the benefits of enoxaparin that allow it to be used in the outpatient setting, as opposed to heparin?

Enoxaparin can be administered subcutaneously, has a longer half-life, and does not need monitoring


Name four toxicities of heparin.

Bleeding, thrombocytopenia, osteoporosis, and drug-drug interactions


During pregnancy, is heparin or warfarin the preferred method of anticoagulation?

Heparin; unlike warfarin, which is a teratogen, heparin does not cross the placenta and thus can be used during pregnancy


What laboratory test can be used to determine if the heparin dose is in the therapeutic range?

The partial thromboplastin time, because heparin activates antithrombin III, which is involved in the intrinsic coagulation pathway


A 70-year-old woman is given prophylactic heparin while hospitalized for pneumonia. Five days later she develops deep vein thromboses and has a low platelet count. What disease is the likely cause of her sudden thrombocytopenic, hypercoagulable state?

Heparin-induced thrombocytopenia; this is an antibody-mediated process that destroys some platelets and overactivates those that remain


Name five clinical uses for heparin.

Immediate anticoagulation for pulmonary embolism, stroke, acute coronary syndrome, myocardial infarction, deep vein thrombosis


What is the mechanism of action of lepirudin or bivalirudin?

These are hirudin derivatives (an anticoagulant produced by leeches) that directly inhibit thrombin


A patient who was started on heparin therapy develops heparin-induced thrombocytopenia; what change should be made to his treatment regimen?

Discontinue the heparin and continue anticoagulation using lepirudin or bivalirudin (direct thrombin inhibitors)


What is the mechanism by which warfarin anticoagulates?

It interferes with normal synthesis and the gamma-carboxylation of the vitamin K-dependent clotting factors II, VII, IX, and X and proteins C and S


What laboratory test is used to determine if a patient taking warfarin is in the therapeutic range?

The prothrombin time will be increased because warfarin affects the EXtrinsic pathway (factor VII) (remember: the EX-PresidenT went to WAR(farin))


What is the therapy of choice for patients who require chronic anticoagulation: heparin or warfarin?

Warfarin; this is preferred to heparin because it can be administered orally


Name four toxicities of warfarin.

Bleeding, teratogenic effects (contraindicated in pregnancy), drug-drug interactions, and skin/tissue necrosis


How is warfarin metabolized?

By the cytochrome P450 pathway in the liver


What is the difference in administration between heparin and warfarin?

Heparin is administered parenterally (intravenously or subcutaneously) whereas warfarin is given orally


What is the difference in the onset of action between heparin and warfarin?

Heparin acts within seconds, whereas warfarin has a slow onset dependent on the half-lives of the normal clotting factors


Describe the treatment of acute warfarin overdose.

Intravenous vitamin K and fresh frozen plasma


Name four drugs that can be used to lyse an existing thrombus.

Thrombolytics include streptokinase, urokinase, tissue plasminogen activator (alteplase), and anisoylated plasminogen streptokinase activator complex (anistreplase)


Which terminal pathway in the coagulation cascade is enhanced by the administration of thrombolytics?

Degradation of fibrin and fibrinogen to fibrin-split-products and deactivation of thrombin


What treatment option can potentially reverse the pathology of an early myocardial infarction or ischemic stroke?

Prompt administration of thrombolytics


What major complication can be seen from the administration of thrombolytics?



Name five contraindications for thrombolytics that are related to increased risk of bleeding.

Patients with active bleeding, a history of intracranial bleeding, recent surgery, known bleeding disorders, or severe hypertension


What is the pharmacologic treatment for thrombolytic toxicity?

Aminocaproic acid, an inhibitor of fibrinolysis; this medication can also be given to hemophiliacs for dental procedures


What is the primary enzymatic reaction that thrombolytics affect?

They either directly or indirectly aid the conversion of plasminogen to plasmin, which initiates fibrinolysis


How do thrombolytics affect the prothrombin time, partial thromboplastin time, and platelet count?

There is an increase in both the prothrombin time and partial thromboplastin time due to deactivation of thrombin, and no effect on the platelet count


How does abciximab downregulate platelet aggregation?

Abciximab is a monoclonal antibody that binds to the glycoprotein receptor IIb/IIIa on activated platelets, thereby preventing aggregation


What is the mechanism of action of aspirin as an anticoagulant?

Aspirin acetylates and irreversibly inhibits cyclooxygenase-1 and cyclooxygenase-2 to prevent the conversion of arachidonic acid to thromboxane A2