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Enoxaparin (Lovenox[R]): an effective and convenient anticoagulant. (Nursing Pharmacology).

In the event of blood vessel damage, the principal function of the body's coagulation system is to maintain hemostasis without actually causing blockage of the vessel. Clotting factors flow through the circulatory system, becoming activated through a series of chemical reactions that lead to the production of fibrin and the formation of a platelet plug. In an opposing effect, anticoagulant medications limit the amount of fibrin formed. This localizes clot formation at the site of damage and prevents widespread thrombosis. Anticoagulants are administered to patients who have been diagnosed with or at high risk for blood clotting complications. Disorders that may necessitate the use of anticoagulants include: myocardial infarction, unstable angina, heart valve replacement, atrial fibrillation, deep vein thrombosis (DVT), and pulmonary embolus. The most commonly used anticoagulants in clinical practice are warfarin, unfractionated heparin (UFH), and low molecular weight heparins (LMWH) (see Table 1).

There are three LMWH agents currently available for use in the United States. These are: ardeparin (Normiflo[R]), dalteparin (Fragmin[R]), and enoxaparin (Lovenox[R]) (Breen, 2000). Each of these medications have been approved by the Food and Drug Administration (FDA) for specific clinical indications, and each is dosed differently. Recent studies have shown that enoxaparin is as effective as unfractionated heparin in preventing and treating DVT. Additionally, enoxaparin is less costly and easier to administer for DVT treatment. Although in the past unfractionated heparin has been the standard anticoagulant administered in the acute care setting, medical-surgical nurses have seen a more widespread use of enoxaparin in both the inpatient and outpatient/home care settings. The pertinent information regarding enoxaparin is reviewed to guide nursing practice across the care continuum.

History and Development of Enoxaparin

Heparin consists of many different sized molecules. LMWH was developed in the 1970s by chemically splitting unfractionated heparin to fractions approximately one-third its original size. Early animal studies demonstrated that this product had an antithrombotic effect equal to unfractionated heparin but caused less bleeding (Noble, Peters, & Goa, 1995). These advantages, combined with the more convenient subcutaneous administration method, led to detailed pharmacological and clinical studies of LMWH. In 1993 the FDA approved enoxaparin for prophylactic treatment of DVT (Hovanessian, 1999). One of the key benefits of LMWH is that while its therapeutic effect is comparable to unfractionated heparin, it is less costly to use for treating DVT. This is because in-hospital days and lab testing are not required (Hovanessian, 1999). Enoxaparin is currently recommended for use in the following conditions: unstable angina, non-Q-wave myocardial infarction, prevention of postoperative DVT for hip and knee replacement, inpatient treatment of DVT both with or without pulmonary embolus, outpatient treatment of DVT without pulmonary embolus, and treatment of acutely ill medical patients (Hovanession, 1999).

Pharmacodynamics

It is necessary to understand the basics of the coagulation cascade in order to recognize the difference between the mechanism of action of unfractionated heparin and enoxaparin (see Figure 1). All steps of the coagulation cascade ultimately lead to the formation of fibrin, which holds a blood clot together. The intrinsic and extrinsic pathways accomplish this goal. Activation of the extrinsic pathway occurs when blood contacts an injured blood vessel. The intrinsic pathway is triggered by the contact between blood and tissue factors that occurs when vessels are damaged by conditions such as diabetes, smoking, hypertension, and hypercholesterolemia. Regardless of which pathway is initiated, the enzyme Factor Xa launches the section of the coagulation cascade known as the common pathway, which is where anticoagulants work. Activated Xa and Factor V serve as the catalysts for the conversion of Factor II (prothrombin) to Factor IIa (thrombin). Thrombin is then responsible for the chemical conversion of fibrinogen to fibrin.

[FIGURE 1 OMITTED]

Unfractionated heparin works by binding with antithrombin III, forming a complex that deactivates thrombin and prevents the conversion of fibrinogen to fibrin (Hovanessian, 1999). In contrast, enoxaparin creates an earlier disruption of the clotting cascade. It prevents the conversion of Factor X to its activated form, Xa, thereby halting the continuation of the common pathway (see Figure 1). Because coagulation is amplified at each step of the cascade, the earlier halting of clotting by enoxaparin makes it a more effective drug.

The anticoagulant effect of unfractionated heparin is monitored by the activated partial thromboplastin time (APTT). This test measures the amount of time required for the intrinsic and common pathways to proceed to the formation of a fibrin clot. The test is very sensitive to the inhibitory effects of heparin on thrombin. When anticoagulation is desired, therapeutic values should be between 1.5 and 2.5 times normal. In contrast, enoxaparin works early in the coagulation cascade and has limited effect on thrombin. Therefore, when this medication is used clinically, traditional laboratory monitoring of the activated partial thromboplastin time is unnecessary.

Pharmacokinetics

"Pharmacokinetics" refers to the absorption, distribution, metabolism, and excretion of a drug in the body. Many variables affect the availability of unfractionated heparin in the body (Hovanessian, 1999). For example, unfractionated heparin binds tightly to proteins in the plasma, causing limited bioavailability and inactivation of some of the compound. Also, unfractionated heparin is metabolized by the liver, making clearance from the body and halflife variable. As a result, it can be difficult to titrate the dose of unfractionated heparin to achieve a therapeutic effect rather than one that is ineffective or has the potential of causing hemorrhagic complications. Each patient's dose must be calculated individually and frequently adjusted based on APTT measurements.

In contrast to unfractionated heparin, the anticoagulant properties of enoxaparin are much more predictable. This is due to its superior bioavailability, a rapid onset of action, a longer half-life, and a clearance rate that is independent of the dose (Hovanessian, 1999). When administered subcutaneously, enoxaparin promptly reaches steady-state plasma concentrations (Noble et al., 1995). Enoxaparin is eliminated from the body via the kidneys, and has a half-life of 4.5 hours, which allows for less frequent administration of the drug.

Researchers have conducted controlled, randomized trials of the use of enoxaparin for treating DVT since 1993 (Hovanessian, 1999). In each case, data show that this medication was at least as safe and effective as unfractionated heparin in preventing further thrombus extension and/or the development of new clots. Further, no significant differences in hemorrhagic complications between the two drugs have been identified. Researchers demonstrated the efficacy, safety, and cost effectiveness of treating DVT at home using enoxaparin (Spyropoulos, Kardos, & Wigal, 2000).

Enoxaparin: Nursing Considerations

Enoxaparin offers greater convenience for the patient and provides the nurse with a more efficient and effective means of care than standard intravenous heparin therapy. When administering this medication, it is not necessary to prepare and monitor IV infusions, draw blood, monitor APTT results, and adjust the medication dose. Instead, hospitalized patients with acute DVT with or without pulmonary embolus need only a subcutaneous injection of 1.5 mg/kg once a day or 1 mg/kg every 12 hours (Noble et al., 1995). For use in the home setting, nursing responsibilities regarding this therapy include teaching the patient about subcutaneous injection technique. Assessment of patients' or family members' cognitive and psychomotor abilities to administer the medication correctly and monitor for potential complications is essential.

Standardized protocols are followed when enoxaparin is initiated (Noble et al., 1995). Warfarin therapy is initiated after the initial enoxaparin dose; the enoxaparin therapy continues for 5 to 7 days while the patient reaches therapeutic anticoagulation levels on warfarin (Noble et al., 1995). This is achieved when the international normalized ratio (INR) is maintained between 2.0 to 3.0. For DVT prevention in patients undergoing hip or knee replacement surgeries, or those undergoing abdominal procedures who have risk of thromboembolic complications, enoxaparin is administered postoperatively at dosages of either 30 mg every 12 hours or 40 mg daily. Enoxaparin is also approved for use in preventing ischemic complications of unstable angina and non-Q-wave myocardial infarction; the recommended dose is 1 mg/kg every 12 hours given concurrently with 100 to 325 mg aspirin daily (Noble et al., 1995).

As with unfractionated heparin, bleeding is the major side effect of enoxaparin. Nursing care includes teaching the patient about this risk, which can be reduced by preventative measures and early assessment. Monitoring for blood in the urine, stool, emesis, and sputum are essential. Signs of dizziness, weakness, severe headache, abdominal pain, and abnormal bruising are signs of occult bleeding that must be reported (Breen, 2000). Bruising at the injection site is a common yet benign occurrence with LMWH use. Heparin-induced thrombocytopenia, defined as a platelet count that drops to 50% of the initial value, can also occur (Hovanessian, 1999). To monitor for this complication, a baseline complete blood count, including the platelet count, is obtained at the onset of this therapy (Breen, 2000). Enoxaparin must be used with caution with patients having a history of endocarditis, hemorrhagic stroke, recent CNS or ophthalmologic surgery, and recent GI hemorrhage or ulceration. Relatedly, health care providers must review other medications that are taken concurrently with LMWH, as drug interactions can occur.

A primary responsibility of medical-surgical nurses is to administer medications and teach patients about them. To do so safely, it is imperative for nurses to be knowledgeable about the latest pharmacologic advances affecting patient care. Given the recent findings regarding the safety, efficacy, convenience, and cost savings of enoxaparin, nurses should expect to see this drug used frequently in clinical practice. Understanding the rational mechanism of action, the appropriate dosage, major side effects, and patient assessments relative to enoxaparin administration is essential for current and safe nursing practice.
Table 1.
Anticoagulant Comparison

            Heparin Sodium         Enoxaparin        Warfarin Sodium

Use        * DVT prophylaxis   * DVT prophylaxis.   * DVT prophylaxis
             and treatment     * Outpatient DVT       and treatment.
           * Coagulopathies      treatment          * Embolus pre-
           * PE prophylaxis      without PE.          vention for
             and treatment     * Inpatient DVT        atrial fibril-
           * DIC                 treatment with       lation and me-
           * Atrial fibril-      or without PE.       chanical valve
             lation with       * Prevention of        replacement.
             embolization        myocardial
                                 ischemia.
                               * Unstable angina.
                               * Non-Q-wave MI.
                               * Acutely ill
                                 medical patient.

Dose/      * DVT prophy-       * Subcutaneous       * PO adminis-
Route        laxis: SC admi-     administration       tration: dose
             nistration:       * Prevention of        adjustments by
             5000 u every        DVT/PE: 30 mg        coagulation
             8-12 hrs.           B1D or 40 mg QD      tests.
           * DVT treatment:    * Treatment of
             IV loading          DVT/PE: 1 mg/kg
             followed in-        B1D or 1.5 mg/kg
             fusion calcula-     QD
             ted by weight
             and adjusted by
             APTT results.

Monitor-   * APTT initially    * None (as APTT &    * INR and/or PT
ing/Labs     measured every      PT are not         * Baseline
             6 hrs; after        altered).            platelets
             dose is adjus-    * Baseline hgb,
             ted, APTT every     hct, & plate-
             24 hrs.             lets.
           * Baseline hgb,     * Anti Xa factor
             hct, and            if renal impair-
             platelets.          ment.

Contra-    * Bleeding          * Bleeding           * Bleeding
indicat-   * HIPA positive     * Thrombocytopenia   * Open wounds
ions       * Increased liver                        * Severe
             function tests.                          hypertension

Antidote   Protamine           Protamine            Vitamin K and
                                                    fresh frozen
                                                    plasma


Acknowledgment: The authors would like to acknowledge Patricia Carroll, MS, RN,C, CEN, RRT, for her assistance in the preparation of this manuscript.

References

Breen, P. (2000). DVT: What every nurse should know. RN, 63(4), 58-63.

Carroll, P. (2000). Treating deep vein thrombosis at home with low molecular weight heparin. Home Healthcare Nurse, (Suppl.), 3-15.

Hovanessian, H. (1999). New generation anticoagulants: The low molecular weight heparins. Annals of Emergency Medicine, 34(6), 768-779.

Noble, S., Peters, D., & Goa, K., (1995). Enoxaparin. A reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease. Drugs, 49(3), 388-410.

Spyropoulos, A., Kardos, J., & Wigal, R (2000). Outcomes analysis of the outpatient treatment of venous thromboembolic disease using low molecular weight heparin enoxaparin in a managed care organization. Journal of Managed Care Pharmacy, 6(4), 298-304.

Stephen Mullaney, BSN, RN, is a Registered Nurse, Rush Medical Center, Chicago, IL.

Marijo Letizia, PhD, RN, is an Assistant Professor, Loyola University, Chicago, IL.

Judith Jennrich, PhD, RN, is an Associate Professor of Nursing, Loyola University, Chicago, IL.
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Author:Mullaney, Stephen; Letizia, Marijo; Jennrich, Judith
Publication:MedSurg Nursing
Geographic Code:1USA
Date:Dec 1, 2001
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