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Enoxaparin is low molecular weight heparin (LMWH) and was first approved for medical use in 1993 and is derived from heparin. It has FDA approval for the following clinical conditions - acute coronary syndromes, deep venous thrombosis (DVT) treatment and prophylaxis, treatment for pulmonary embolism (PE), venous thromboembolism (VTE) treatment, and prophylaxis in a variety of scenarios, percutaneous coronary intervention (PCI), and periprocedural anticoagulation, among others. This activity will highlight the mechanism of action, adverse event profile, pharmacology, monitoring, and relevant interactions of enoxaparin, pertinent for interprofessional team members in treating patients with conditions where this agent is indicated. Objectives: Describe the therapeutic mechanism of action of enoxaparin. Review the many indications for enoxaparin use. Summarize the adverse event profile of enoxaparin use. Explain the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients when using enoxaparin. Access free multiple choice questions on this topic.

Clinical practice guidelines recommend protamine sulfate for the reversal of enoxaparin-associated bleeds dependent on the time from the last administration and dose of enoxaparin. Protamine sulfate is a cationic peptide that binds to low molecular weight heparin, forming an ionic complex with no anticoagulant activity.[45] The use of protamine sulfate correlates with fewer bleeding complications post PCI. As with most anticoagulants, bleeding is the major complication with low molecular weight heparin-like enoxaparin. The incidence rate is reported to be less than 3%. Given the subcutaneous administration of LMWH, there is a high risk of minor bruising at the injection site. The subcutaneous injection has a bioavailability of around 100%. In the event of significant bleeding, protamine sulfate can be used to reverse the anticoagulant effects of LMWH partially. Protamine neutralizes about 60% of LMWH anticoagulant activity. For LMWH administered within the previous 8 hours, the recommended dose is 1mg protamine sulfate per 1mg of enoxaparin or 100 anti-factor-Xa units of dalteparin.[42] According to the ACCP guidelines, the maximum single dose of protamine sulfate is 50 mg. If bleeding persists, a second dose of 50 mg protamine sulfate can be administered. Smaller doses of protamine sulfate can be administered if the time since LMWH administration is greater than 8 hours.[43] Universal Heparin Reversal Agent (UHRA) is specifically invented to neutralize the activity of heparin-based anticoagulants. UHRA is a synthetic multivalent polymer that is currently in clinical trials. The preliminary results are promising, showing that UHRA directly binds UFH and enoxaparin and can reverse the activity of heparin and enoxaparin.[46]

According to the ACCP guidelines, the maximum single dose of protamine sulfate is 50 mg. If bleeding persists, a second dose of 50 mg protamine sulfate can be administered. Smaller doses of protamine sulfate can be administered if the time since LMWH administration is greater than 8 hours.[43] Universal Heparin Reversal Agent (UHRA) is specifically invented to neutralize the activity of heparin-based anticoagulants. UHRA is a synthetic multivalent polymer that is currently in clinical trials. The preliminary results are promising, showing that UHRA directly binds UFH and enoxaparin and can reverse the activity of heparin and enoxaparin.[46] Heparin-induced thrombocytopenia is an infrequent but potentially life-threatening complication of enoxaparin therapy. The development of antibodies against heparin-bound platelet factor 4 (PF4) generally occurs 5–10 days after administration. The antibody-heparin-PF4 complex binds and activates platelets resulting in thrombosis and thrombocytopenia. 4T score (thrombocytopenia, timing of platelet count fall, thrombosis, other causes of thrombocytopenia), serotonin release assay, and anti-PF4/heparin antibodies are used for diagnosis.[47][48] Argatroban and lepirudin direct thrombin inhibitors are FDA-approved for the treatment of HIT.[49] Argatroban therapy decreased amputation, thrombotic complications, and mortality in clinical trials. Bivalirudin is used for patients undergoing percutaneous cardiac intervention having HIT or at risk for developing HIT. (American society of hematology)[22]

Managing bleeding complications of enoxaparin is challenging. It requires collaboration between interprofessional health care team members such as clinicians (MD, DO, NP, PA), specialists, nurses, laboratory technicians, and pharmacists. The management of bleeding should not be delayed, and intervention should ensue as soon as possible. A blood bank should be contacted for the potential need for an urgent transfusion. As discussed above, protamine sulfate is the drug of choice in this situation. A conservative approach is necessary for the consideration of acute bleeding. Anticoagulation should be stopped with the reversal of anticoagulation. Fluid resuscitation is also essential if the patient is hemodynamically unstable. The nurse should explain the procedure to the patient if the clinician prescribes enoxaparin for home administration. The pharmacist should consult with the prescriber regarding dosing; this should be with the initial prescription of enoxaparin and protamine in the event of reversal. The patient should receive education to report to the emergency department if any signs or symptoms of bleeding occur. Interprofessional collaboration is vital to improving patient outcomes related to enoxaparin therapy. All team members must maintain open communication with the rest of the care team and keep accurate records regarding enoxaparin therapy. The study reported a significant decrease in venous thromboembolism in hospitalized patients with an interprofessional team of hospitalists, intensivists, vascular, trauma, orthopedic surgeons, nurses, an inpatient pharmacy director, and a clinical pharmacist.[50] [Level 5]