As 2007 came to a close, another anticoagulation error received widespread coverage: The newborn twins of actor Dennis Quaid and his wife, Kimberly, received 1,000 times the prescribed dose of the anticoagulation medication heparin. A third newborn in the same California hospital received an overdose of heparin, as well. Luckily, none of the newborns suffered lasting effects.1 These medication errors were similar to one in Indiana in 2006, when a pharmacy technician mistakenly stocked 10,000 units/mL vials of heparin in a medication drawer in the newborn nursery where 10 units/mL vials were normally stored. Three newborns received erroneous doses and died. Many experts believe these safety gaps will help shape new safety systems specific to anticoagulation therapy.1,2

Safety in systems
Patient safety used to be considered the individual nurse’s responsibility. But evidence is growing about the importance of safe systems,3 and organizations such as The Joint Commission and Quality and Safety Education for Nurses are helping healthcare providers develop systems for safer care. A key part of this effort is the annual updating of The Joint Commission’s National Patient Safety Goals. (The NPSGs are determined after a review of sentinel events tracked nationally.) For 2008, one update is the expansion of NPSG 3 (improve the safety of using medications) to include reducing the likelihood of patient harm associated with the use of anticoagulation therapy. Nurses must be knowledgeable about anticoagulants to ensure safe practice.

Used to prevent or treat deep vein thrombosis (DVT), anticoagulants are high-alert medications that pose a risk of injury or death if not used correctly. Mistakes with anticoagulants do not necessarily occur more frequently than with other drugs, but the consequences are more devastating.5 Most hospitalized patients receive anticoagulants because of the risk of DVT that can result from immobility. But most patients have more than one risk factor. General risk factors include increased age, obesity, smoking, a history of DVT, acute illness, indwelling central venous catheters, surgery, estrogen therapy, cancer and cancer therapy, inflammatory conditions, acute infectious processes, heart failure, chronic lung disease, stroke, and varicose veins.6

A DVT places patients at high risk for a pulmonary embolism. (If not treated, PE has a fatality rate of about 25%.7) A DVT also increases costs to the patient and healthcare system, e.g., the patient with a DVT must undergo diagnostic procedures and spend more time in the hospital.6,8 New evidence demonstrates that traditional physical assessment for DVT, including Homans’ sign (pain in the lower leg with dorsiflexion of the foot), is neither sensitive nor accurate in detecting DVTs.9

Unfractionated heparin and low-molecular weight heparin (LMWH) are the most common treatment regimens to prevent DVT in the acute care setting, reducing DVT risk by up to 50%.8 Each targets a different area of the coagulation cascade to stop development of thrombi, but they don’t dissolve existing thrombi. If a patient needs ongoing anticoagulation after discharge, warfarin (Coumadin) is the most common oral agent.10

Unfractionated
Patients receive unfractionated heparin subcutaneously for DVT prophylaxis. Hospitalized patients with fewer risk factors for DVT need twice daily dosing of 5,000 units. High-risk patients may require three daily doses of 5,000 units.10,11 When administering heparin, inject it into the subcutaneous tissue of the abdomen and rotate sites for each injection. Do not aspirate or massage. Unfractionated heparin should not be given intramuscularly, because of the risk of hematoma. Assess the subcutaneous injection sites for hematomas, ecchymosis, and inflammation.11

IV infusion of unfractionated heparin is used to treat DVT and embolization from atrial fibrillation and for patients in A-fib for over 48 hours as a means to prevent thrombi. A loading dose (35 to 70 units/kg) is usually administered before beginning a continuous infusion (15 to 18 units/kg/hr).11 Heparin infusion is usually adjusted based on a standardized heparin protocol. Many hospitals require two RNs to double-check the IV bolus and dosing of continuous IV heparin. An IV pump must be used to administer continuous IV heparin.

In case of overdose
Protamine sulfate (1% solution) is the antidote for heparin. When bleeding requires the reversal of heparin, no more than 50 mg of protamine sulfate should be slowly administered over 10 minutes. Each milligram of protamine sulfate neutralizes about 100 units of heparin.12 However, because of heparin’s short half life (one to two hours), an overdose can often be treated by stopping the medication.10

It’s important to note that some research showed that protamine sulfate may put patients who are on NPH insulin at increased risk of developing a serious adverse reaction such as anaphylaxis.13

Baseline lab studies (such as hemoglobin, hematocrit, activated partial thromboplastin time [aPTT], and platelet count) should be obtained before heparin therapy starts. Platelet counts should be checked every two or three days throughout therapy. A brief drop in platelet count relative to the baseline value occurs in 10% to 20% of patients and is not dangerous.14,15 (Normal platelet counts in adults are 150,000 µl/mm3 to 400,000 µl/mm.3) However, a platelet count of less than 100,000 µl/mm3 within five days after heparin therapy has started, a condition called heparin-induced thrombocytopenia, can be life-threatening.7 HIT occurs in about 5% of patients on heparin. Part of the risk of HIT is its reoccurrence any time a patient is re-exposed to any form of heparin. Therefore, HIT should be a prominent incident in the patient’s history, and heparin should be listed as an allergy.

Heparin’s ongoing anticoagulative effect can be monitored by aPTT values or activated clotting times (ACT); however, aPTT values are used more often.10 When intermittent IV heparin therapy is used, draw an aPTT level 30 minutes before each dose during initial therapy and then periodically. For continuous IV heparin, monitor the aPTT every four hours during early therapy. For subcutaneous administration, the aPTT should be drawn four to six hours after injection.11 A normal aPTT is 24 to 36 seconds, with a therapeutic value of 46 to 70 seconds for a patient on heparin.15 The frequency of aPTTs and therapeutic values may depend on hospital protocols and will vary depending on the indication for heparin (e.g., if heparin is ordered for the treatment of acute MI, ischemic stroke, or a PE). The normal ACT value is 80 to 135 seconds; a therapeutic value for a patient on heparin is three minutes.15

Low weight
Low-molecular weight heparin, such as enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep), can be used for DVT prophylaxis, DVT treatment, or treatment of some cardiac conditions, such as unstable angina. Enoxaparin is the most common LMWH in acute care.

LMWH is generally administered subcutaneouly. Enoxaparin, however, may be given IV to patients with specific cardiac events as outlined by ACLS guidelines.16 For DVT prophylaxis, LMWH has a longer half life than unfractionated heparin, usually requiring fewer injections.11 Dosing of LMWH for DVT prophylaxis doesn’t depend on weight; therefore, laboratory monitoring is not required, and thrombocytopenia is less likely.8 (Dosing of LMWH is weight-based in other conditions, e.g., DVT treatment, unstable angina, and non-Q wave MI.) However, the patient is still at risk for HIT. When administering subcutaneous LMWH, do not expel the air bubble from the prefilled syringe before injecting the medication, because of potential medication loss. In all other aspects, subcutaneous administration of LMWH can follow the same guidelines as those for unfractionated heparin.

The antidote
The antidote for LMWH is protamine sulfate. The following overdose guidelines can be used for enoxaparin, which has a half life of three to six hours: Treat with slow injection (over 10 minutes) of protamine sulfate (1% solution) 1 mg IV for every 1 mg enoxaparin if enoxaparin was administered in the previous eight hours. An infusion of 1/2 mg protamine sulfate per 1 mg of enoxaparin may be administered if enoxaparin was administered more than eight hours previously. A second infusion of 1/2 mg protamine sulfate per 1 mg of enoxaparin may be administered if the aPTT measured two to four hours after the first infusion remains prolonged. After 12 hours from the time of enoxaparin injection, protamine sulfate may not be required.11

Before initiating any LMWH therapy, baseline laboratory studies should be collected, including CBC; platelet count (a baseline is needed in the event of HIT); PT/INR; aPTT (e.g., if the patient has a pre-existing coagulopathy); and creatinine clearance. Patients with poor renal function (a creatinine clearance less than 30 mL/minute) must receive lower dosages of LMWH because the medication is partially excreted by kidneys.10 (Normal values for creatinine clearance for men are 95 to 135 mL/minute; the normal values for women are 85 to 125 mL/minute.)14 Because LMWH acts on a different part of the coagulation cascade, a patient’s aPTT and ACT are not monitored.17

During LMWH therapy, review the patient’s platelet count and hematocrit. If an unexplained thrombocytopenia occurs, notify the healthcare team and monitor the platelet count closely. Any decrease in the platelet count below 100,000 µl/mm3 is significant. Similarly, if a patient’s hematocrit suddenly drops, assess the patient for potential bleeding sites and hold the medication.11

G.B., a 36-year-old woman, is admitted to your medical floor directly from her primary care physician’s office with the diagnosis of asthma exacerbation. Her vital signs are 134/88, 94, 28, 99.4, and 88% oxygen saturation on room air. You place her on two liters of oxygen via nasal cannula, and her oxygen saturation rises to 95%, and her respiratory rate decreases to 22 respirations/minute. You auscultate G.B.’s lungs, and she has expiratory wheezes with diminished breath sounds in the lower lobes bilaterally. During the admission process, G.B. tells you that along with chronic asthma, she suffers from hypertension, for which she takes lisinopril (Prinivil) 10 mg daily. She uses a fluticasone (Flonase) aerosol inhaler twice a day to keep her asthma under control. In addition, she was just diagnosed with Type 2 diabetes and takes 500 mg metformin (Glucophage) by mouth twice daily. G.B. weighs 220 pounds and is 5 feet 8 inches tall. Her BMI is 33.4 (a BMI over 30 qualifies G.B. as obese). G.B. takes oral contraceptives every morning.

1. The physician who will be caring for G.B. calls you from the ICU
and says that he will be up to see G.B. later in the shift. You
report that G.B.’s respiratory status is stable. The physician
asks you about G.B.’s risk for DVT. You respond that —
a. Her risk is low.
b. Her risk is high.
c. You don’t have to worry about DVT risk because she is
being admitted for an asthma exacerbation.
d. Her risk cannot be assessed at this time.

2. The physician starts G.B. on 40 mg enoxaparin subcutaneously
each day. Which baseline labs will you want drawn before you
begin this prophylactic treatment for DVT?
a. A CBC and liver function labs
b. A CBC and creatinine clearance
c. A creatinine clearance and aPTT
d. Liver function labs and a PTT

3. G.B.’s baseline platelet count was 150,000 ml/mm<sup>3<\
sup> at admission. Two days later, before administering the
0900 dose of enoxaparin, you discover that her platelet count
is 85,000 ml/mm³. What is your response to this
drop in platelet count?
a. You give the 0900 dose of enoxaparin anyway.
b. You wonder whether she is becoming dehydrated and check the specific gravity of her urine.
c. Concerned about this thrombocytopenia, you hold the dose of enoxaparin and call the physician.
d. You call the physician, requesting to change G.B. to
subcutaneous heparin.

4. G.B. complains of a headache and asks for an analgesic.
Which analgesic would be best for this patient?
a. Aspirin
b. Ibuprofen
c. Acetaminophen
d. Naproxen

Warfarin: the oral anticoagulant
A vitamin K antagonist, warfarin is the most common oral anticoagulant. Predominantly used as an outpatient anticoagulant, it’s prescribed to prevent and treat thrombi, and is often used with patients who have atrial fibrillation, a cardiac pacemaker, or heart valve replacements.18 Warfarin interferes with hepatic synthesis of vitamin K-dependent clotting factors.11 The blood test for monitoring warfarin is a prothrombin time. Because of variation between reagents used in laboratories, PT results are reported as an international normalized ratio. The INR is an international standardized test for PT, meant to be used with patients on long-term warfarin therapy.18

An INR for a person not receiving anticoagulants is 0.9 to 1.1. The therapeutic range for preventing thrombus formation is 2.0 to 3.0.19 For patients receiving warfarin for atrial fibrillation, the American College of Chest Physicians recommends an INR between 2.0 and 3.0.20 Dosing of warfarin for patients with prosthetic cardiac valves depends upon the kind of valve and its placement in the heart. Target INR values for these patients are between 2.5 and 3.0.21 Adult dose ranges of warfarin are from 2.5 mg/day to 10 mg/day, and they are then adjusted by results of the INR.11

In monitoring for adverse effects of warfarin, the most important time is at the beginning of treatment. Possible adverse effects include hemorrhage, GI bleeding, and a rarely occurring anticoagulant-induced skin necrosis. Lesions associated with skin necrosis generally appear within 10 days of beginning warfarin therapy. The lesions generally appear on the breast, buttock, abdomen, or thigh. Pain is often the first symptom, and petechiae progress to hemorrhagic bullae (large vesicles filled with blood), hemorrhagic infarction (a clot that compromises circulation in the area), and full-blown necrotic eschar.22 The best way to prevent warfarin-induced skin necrosis is identification of populations at risk, primarily obese, middle-aged women. The female-to-male ration is 9:1.3.22 Excessive anticoagulation may be controlled by discontinuing warfarin, or if anticoagulation needs to be immediately reversed, by administering phytonadione (vitamin K). With significant bleeding, give 5 mg to 25 mg of parenteral vitamin K. (On rare occasions, up to 50 mg is needed.) In case of severe hemorrhage, clotting factors can be returned to normal by administering fresh whole blood or fresh frozen plasma.23

From asparagus to yogurt
Food interactions with warfarin are many and important to review with patients. Foods that contain vitamin K (including asparagus, beans, broccoli, cabbage, cheese, fish, milk, rice, spinach, and yogurt) reduce the anticoagulant effect of warfarin.18 Eating a consistent amount of foods containing vitamin K can reduce its effects on anticoagulation. Another important dietary interaction occurs with alcohol; chronic use and binge drinking can alter the therapeutic levels of warfarin.23

Interactions can occur between a variety of medications and warfarin, with some reducing clotting factors and interfering with vitamin K metabolism.18 Medications that reduce the anticoagulant effect of warfarin include phenobarbital (Luminal), nitroglycerin (Nitro-Bid), digitalis (Digoxin), and carbamazepine (Tegretol). And although not a medication, nicotine can have a reductive effect on warfarin. Medications that can increase the effect of anticoagulants include many antibiotics (including several aminoglycosides, penicillins, and cephalosporins); all nonsteroidal antiinflammatory drugs (NSAIDs); acetaminophen (Tylenol); glucagon (Gluca Gen); cimetidine (Tagamet); omeprazole (Prilosec); fluconazole (Diflucan); and medications that contain aspirin (e.g., Excedrin, Bufferin, and Nyquil).18 Many herbal products interact with warfarin, as well; St. John’s wort, garlic, ginko, and ginseng green tea may contribute to increased bleeding.11 Carefully review all medications and herbal supplements that a patient on warfarin is taking to assess for deleterious interactions.18

A patient who has been anticoagulated in the hospital with heparin or LMWH and needs to remain on an anticoagulant after discharge may be treated with concomitant heparin and warfarin therapy. Heparin or LMWH “bridging” to warfarin improves the efficacy and safety of oral warfarin therapy.24 To maintain continuous anticoagulation, it’s advisable to continue full-dose heparin therapy while overlapping with four or five days of warfarin. When warfarin has produced the desired PT/INR, heparin may be discontinued.23 As mentioned, the blood test for monitoring warfarin’s anticoagulation effects is PT/INR. Patients new to warfarin may have their PT/INR level checked every day. Once patients reach the therapeutic range appropriate for their anticoagulation needs, the PT/INR can be checked over longer intervals, weekly or monthly for most patients. Because of the many outside variables that can affect warfarin’s anticoagulation, patients must have their PT/INR drawn on schedule.18

Anti-anticoagulation
Any assessment finding that indicates a patient is at increased risk for bleeding is a possible contraindication for anticoagulation therapy. The healthcare team should assess whether the patient has active bleeding (e.g., GI bleed, trauma, or intracranial hemorrhage). Is there a history of HIT? If the patient is thrombocytopenic (platelet count under 100,000 µl/mm3), pharmacologic approaches to anticoagulation are too dangerous. A thorough review of the patient’s medications is needed, with a focus on any oral anticoagulants or platelet inhibitors (e.g., NSAIDs, clopidogrel [Plavix], and salicylates).8 Mixing two anticoagulants or taking platelet inhibitors with anticoagulants is not advised. Because of the renal excretion of LMWH, the patient’s creatinine clearance must be within the normal limits.

Any history of hemorrhage must be carefully reviewed to assess the patient’s risk of bleeding. Will the patient be going to surgery in the immediate future? Patients awaiting surgery are not good candidates for anticoagulation therapy. Caution should be exercised in using anticoagulants with a patient whose history includes bleeding disorders, GI bleeds, or hemorrhagic strokes.

Contraindications for warfarin are similar as those for heparin and LMWH. Any patient who demonstrates bleeding abnormalities is not a good candidate for warfarin. Additionally, women who are or may become pregnant should not take warfarin, because it passes through the placenta and may cause fatal hemorrhage to the fetus or birth malformations.23 Patients with compromised liver function may not be candidates for warfarin. Liver disease decreases the synthesis of clotting factors, so an increased anticoagulant effect is seen in patients with significant liver disease.16 Warfarin may not be the appropriate anticoagulant for a patient with an infection, because the expected decrease in white blood cells that occurs with warfarin therapy can intensify the patient’s risk for more serious infection.18

Where RNs fit in
One of the first priorities in the hospital is to assess a patient’s risk for DVT. The choice and dose of anticoagulant depend on the risk factors for developing a DVT.

One of the highest risks of anticoagulation therapy is the unintended concurrent use of two heparin products (e.g., unfractionated and LMWH heparin), which has resulted in serious harm or death.11 The nurse must review the patient’s recent and current medication administration records before giving any heparin or LMWH product. Concomitant use of heparin or LMWH with warfarin is acceptable, especially for patients being transitioned from heparin to warfarin.

IV administration of heparin also requires careful attention. IV heparin should be administered only with an IV pump, and two RNS should check the bolus dose and the continuous IV dose.

Since heparin is available in various concentrations for varying uses, nurses need ensure that the proper concentration is used for anticoagulation. Bar code tracking of medications or two clinical verification processes can help prevent errors. Lab monitoring is important for all patients on anticoagulation, as outlined earlier.

Once patients are on an anticoagulation regimen, the nurse must assess them on a consistent basis for frank or occult bleeding, including gingival bleeding, epistaxis, ecchymosis, hematemesis, hematochezia, black tarry stools, or hematuria. A sudden drop in blood pressure, especially orthostatic hypotension, or in hematocrit may suggest bleeding. Continue to assess for thrombosis. Swelling in a unilateral extremity or increased pain in a leg may be secondary to the formation of a thrombus. As with all medication administration, continually evaluate patients for hypersensitivity to the anticoagulant, such as chills, fever, or hives (urticaria).15

All clear
Clear communication with all members of the healthcare team is important in caring for patients on anticoagulants, and patient safety systems enhance communication. A thorough medication reconciliation during the patient’s care will contribute to effective communication. In addition, all members of the healthcare team must know which patients are receiving anticoagulant therapy, especially those performing blood draws and placing peripheral and central invasive catheters. Additional pressure is needed for venipuncture and injection sites to prevent bleeding or hematoma. IM injections should be avoided.

Patient teaching about anticoagulants should begin at admission as providers assess DVT risk. Once therapy begins, patients should know why they are on anticoagulants and why they are so important for overall health. The nurse should explain potential adverse effects and instruct patients to report unusual bleeding or bruising. Patients and families benefit from understanding lab values monitored during hospitalization. Patients who understand the importance of DVT prophylaxis will be more apt to participate in nonpharmacologic approaches, such as frequent ambulation and use of pneumatic compression devices while in bed.

Educating patients on warfarin should begin well before discharge. Stress the importance of timely PT/INR draws and educate patients about food, medication, and herbal interactions. Advise patients to wear identification bracelets indicating they are on anticoagulant therapy.

As hospitals seek to avoid harm to patients from anticoagulation therapy, knowledgeable bedside clinicians will be important contributors to the safety processes that emerge.

Gail Armstrong, RN, ND, is an assistant professor at the University of Colorado Denver School of Nursing and a med/surg nurse at a Denver area hospital. The University of Colorado Denver School of Nursing is a pilot school for the national Quality and Safety Education for Nurses project, and Armstrong’s work includes updating prelicensure clinical courses to reflect quality and safety trends in healthcare delivery. The author has declared no real or perceived conflicts of interest that relate to this educational activity. Nursing Spectrum Continuing Education guarantees that this educational activity is free from bias.

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EDITORS NOTE: References and Bibliography are available online at www.nurse.com/ce.