View Entire Collection
By Clinical Topic
By State Requirement
Diabetes – Summer 2012
Future of Nursing Initiative
Heart Failure - Fall 2011
Influenza - Winter 2011
Nursing Ethics - Fall 2011
Trauma - Fall 2010
Traumatic Brain Injury - Fall 2010
Fluids & Electrolytes
Anticoagulation therapy can be used to prevent or treat a variety of conditions, from venous thromboembolism (VTE) to atrial fibrillation (AF), ischemic stroke, and acute coronary syndromes (ACS). The challenges are in understanding all of the different anticoagulants, which ones to use when, and how to keep patients safe during anticoagulant therapy. The ultimate goal is to prevent thrombi while minimizing the risk of bleeding.
Our current drugs, while effective, are difficult to manage. Vitamin K antagonists (VKAs) have a narrow therapeutic window requiring frequent monitoring, a delayed onset of action, and many food and drug interactions. Low-molecular-weight heparins (LMWHs) are affected by the patient's renal clearance. And among other challenges, unfractionated heparin (UFH) has a nonlinear dose-response curve; that is, the therapeutic levels in patients receiving UFH aren't always related to their dose of heparin or their activated partial thromboplastin time.
The ideal anticoagulant should be safe and effective; have a linear dose-response curve; have a wide therapeutic range; be a single daily dose (preferably oral); have rapid onset of action; require little or no monitoring; have no food or drug interactions; have limited renal elimination; have an appropriate antidote; be synthetic (eliminating the variability found in anticoagulants produced from animal products); and have a reasonable cost.1
To understand how anticoagulants work, you need to review how a thrombus is formed. Two simultaneous processes are at work here: the coagulation cascade and platelet activity.
Vessel injury triggers the release of tissue factor, which stimulates the coagulation cascade and converts prothrombin to thrombin. Thrombin, acting as an enzyme, converts fibrinogen to fibrin (the material that stabilizes the clot).
At the same time that blood coagulation is occurring, platelets are being exposed to a variety of subendothelial proteins, such as collagen, adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin. This causes the platelets to change shape and express receptor sites for glycoproteins (GP) IIb/IIIa. At these receptor sites, fibrinogen binds platelets to each other (platelet aggregation). These platelets are then covered by a fibrin mesh (created by the coagulation cascade), forming a thrombus (see Forming the platelet plug).2
Anticoagulants stop thrombus formation by interfering with the coagulation cascade; antiplatelet agents interfere with the platelet activation process, such as platelet aggregation (see Sites of antithrombotic drug actions).3 This article focuses on the pharmacologic agents that interfere with the coagulation cascade.
Be sure to consult a drug reference or your facility's pharmacist before administering these drugs.
* UFH is an animal-derived parenteral agent that's been available for almost 100 years.4 UFH's long molecular chain binds to antithrombin (AT) via a pentasaccharide sequence before binding to thrombin to prevent both the conversion of fibrinogen to fibrin and the activation of platelets. UFH binds to many other things besides AT (such as platelets), which contributes to its varied dose response. UFH has a variable dose-response curve: even using weight-based heparin, clinicians might not get the same therapeutic level from giving the same dose to the same patient at a different time. The variability of the response is because the drug is animal-derived and not synthetic in origin. Because of this, patients on UFH need frequent blood monitoring and dose adjustments.
UFH is indicated for the prophylaxis and treatment of a variety of thromboembolic issues. The drug's rapid onset of action can be reversed by protamine sulfate. Bleeding is a common complication of UFH administration. Heparin-induced thrombocytopenia can also be a complication and platelet levels should be monitored on a regular basis during the course of treatment.1
* LMWHs have smaller molecular chains, so they bind more efficiently and have better bioavailability (a measure of the extent of the drug's absorption by a given route) than UFH. LMWH activates AT to inactivate factor Xa. So it works higher in the coagulation cascade than UFH. If overcoagulation is suspected, a serum anti-Xa level can be obtained.
LMWHs can be used for prophylaxis or treatment of VTE and to prevent complications of ACS. Drugs in this class include enoxaparin, dalteparin, and tinzaparin.5 A generic enoxaparin is approved for multiple indications.
The longer half-lives of LMWHs mean patients can take subcutaneous doses once or twice a day. And because more of the drug binds to AT, LMWHs have a more predictable response, which in turn makes coagulation monitoring unnecessary. As a result, LMWHs can be used in outpatient settings.
* Fondaparinux is a first-generation synthetic analogue of the AT-binding pentasaccharide found in heparin and LMWH that binds to AT to inhibit factor Xa.3 Fondaparinux is indicated for thromboprophylaxis, ACS, and treatment of VTE.1,6 Administered subcutaneously once daily, it has a predictable anticoagulant response.
* As their name implies, direct thrombin inhibitors prevent thrombin from converting fibrinogen into fibrin. Because the drugs work directly on thrombin, they're indicated for patients with heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) or a history of HIT or HITTS.7
The two drugs in this class, bivalirudin and argatroban, are used in place of heparins. Bivalirudin is used in patients with ACS who are undergoing percutaneous coronary intervention (PCI). Argatroban, a synthetic direct thrombin inhibitor, is indicated for prophylaxis and treatment of patients with HIT, and as an anticoagulant in patients with or at risk for HIT who are undergoing PCI.
* VKAs include warfarin, and act by inhibiting the vitamin K-dependent coagulation factors II, VII, IX, and X. Indications for VKAs include prophylaxis and treatment of VTE; prophylaxis and treatment of thromboembolic complications of AF and cardiac valve replacement; and for reducing the risk of death, recurrent myocardial infarction (MI), or stroke after MI.8
Warfarin has a delayed onset of action, multiple food and drug interactions, and a very narrow therapeutic window. Patient response to warfarin is ensured by monitoring the prothrombin time (PT) and international normalized ratio (INR). The therapeutic PT/INR depends on the indication for warfarin use.5
Now let's look at four new drugs for anticoagulation.
* Dabigatran is an oral direct thrombin inhibitor indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. This drug is given twice daily without regard to food, and is dose-adjusted for patients with renal dysfunction.5 Dabigatran has a better drug interaction profile as compared to VKAs. The most common adverse reactions are bleeding and gastrointestinal effects. No antidotes are available for dabigatran.2
* Rivaroxaban is an oral factor Xa inhibitor approved for VTE prophylaxis after orthopedic surgery.1 The drug also is indicated to reduce the risk of VTE and stroke in patients with nonvalvular AF. Rivaroxaban has high bioavailability, rapid onset of action, and low incidence of drug-drug interactions. The drug can be taken without regard to food; the most common adverse reaction is bleeding.2
* Apixaban and edoxaban are factor Xa inhibitors that are in phase III clinical trials. These drugs are indicated for VTE prophylaxis, AF, and ACS.1
So to review, the factor Xa inhibitors work higher in the coagulation cascade than the direct thrombin inhibitors. What remains unclear is whether upstream inhibition is any safer or more effective than downstream blockade. We do know that the benefits of the newer agents are the ease of administration without the need for frequent monitoring, as well as fewer drug-drug and food-drug interactions. Although bleeding remains a common adverse reaction to new and old agents, the newer agents are at least as safe as the older agents. Future studies will show the real-life efficacy and safety profiles of new agents.1
Patients who are at increased risk for bleeding include those who
* are 65 or older
* have a history of bleeding disorders
* have a history of anemia
* have a history of renal impairment
* are concurrently using other drugs (such as antiplatelet drugs and nonsteroidal anti-inflammatory drugs) that could potentiate the effects of anticoagulants.
In addition to assessing patient risk factors, monitor vital signs, assessing for hypotension and tachycardia; monitor lab results for anemia and thrombocytopenia, and assess the patient for signs and symptoms of bleeding, including bleeding gums, ecchymoses, petechiae, epistaxis, hematuria, change in mental status, and hematomas. Perform vigilant medication reconciliation to identify medications that could potentiate or inhibit the anticoagulant's effects.
Teach your patient about bleeding risks and bleeding precautions (such as the use of a soft toothbrush and electric razor, and other ways to minimize the risk of injury). Review dietary considerations if appropriate, and potential drug interactions, especially over-the-counter medications. Teach the patient about home safety and fall prevention, to watch for signs of bleeding, and encourage him or her to wear a medical alert tag or bracelet.5
By understanding the old and new anticoagulants and how they work, you can help your patient get appropriate therapy.
1. Denas G, Vittorio P. Emerging anticoagulants. Expert Opin Emerg Drugs. 2011;16(1):31-44. [Context Link]
2. Fareed J, Thethi I, Hoppensteadt D. Old versus new oral anticoagulants: focus on pharmacology. Annu Rev Pharmacol Toxicol. 2012;52:79-99. [Context Link]
3. Hirsh J, Guyatt GH, Albers GW, Harrinton RA, Schunemann HJ. Antithrombotic and thrombotic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133(suppl 6):110S-1112S. [Context Link]
4. Mannucci P, Fanchini M. Old and new anticoagulant drugs: a minireview. Ann Med. 2011;43(2):116-123. [Context Link]
5. Pezzotti W, Frueler M. Using anticoagulants to steer clear of clots. Nursing. 2012;42(2):26-34. [Context Link]
6. Wright RS, Anderson JL, Adams CD, et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):1920-1959. [Context Link]
7. McCarron K. Stop that clot! Anticoagulant medications 101. Nursing made Incredibly Easy! 2010;8(5):30-40. [Context Link]
8. Warfarin prescribing information. Bristol-Myers Squibb Pharma Co., Princeton, NJ. 2011. http://packageinserts.bms.com/pi/pi_coumadin.pdf. [Context Link]
Sign up for our free enewsletters to stay up-to-date in your area of practice - or take a look at an archive of prior issues
Join our CESaver program to earn up to 100 contact hours for only $34.95
Explore a world of online resources
Back to Top