Enoxaparin is a low-molecular weight heparin (LMWH). Because of its lower protein-binding compared to unfractionated heparin (UFH), enoxaparin has more predictable pharmacokinetics and less need for therapeutic monitoring. Enoxaparin is frequently used as prophylaxis for deep venous thrombosis (DVT) in critically ill human patients. The ideal prophylactic regimen in critical care patients is still unclear and remains highly investigated. Individual patient factors (such as BMI and renal function) alter drug metabolism and, therefore, serum drug level monitoring to achieve a target anti-Xa factor blood level is ideal in higher risk patients. The availability of drug monitoring is poor and impractical in most veterinary settings. Thus recommendations for dose, route, and interval of administration in veterinary patients are extrapolated from those used in human patients. The ideal application, dosing guideline, and safety in veterinary patients remain unknown.
Mechanism of action
Heparin and LMW-heparins prevent clot formation by binding antithrombin. The heparin-antithrombin complex can then bind to and inactivate either thrombin (Factor II) or activated-Factor Xa. Low-molecular weight heparin will only bind and inactivate activated Factor Xa.
Derivation and metabolism
- Derived from heparin to yield fragments one third the size of heparin. Mean LMWH size: 4500-5000 Da
- Metabolism: Hepatic metabolism via breakdown to less biologically active molecules. Approximately 10% of the active drug is renally excreted.
- Maximum anti-Xa and anti-thrombin activity occurs 3-5 hours after administration. Steady state achieved after 24 hours of therapy
- Elimination half-life 4.5 hours (single dose) or 7 hours (repeated doses)
Benefits of LMWHs
- Lower binding properties than unfractionated heparin (UFH). Reduced binding to plasma proteins and cells is responsible for the more predictable dose-response
- Reduced ability to inactivate thrombin (Factor II) because the smaller fragments cannot bind simultaneously to antithrombin (AT) and thrombin
- Nearly equal ability to inactivate factor Xa as heparin, despite smaller molecule size
- Longer plasma half-life (compared with UFH)
- Lower risk of heparin-induced thrombocytopenia and osteopenia
- 1 mg/kg SQ q12hrs – preferable dosing regimen unless renal disease, obesity, or emaciation
- Consider reduction of dose in the above patient population (0.7 mg/kg BID OR 1 mg/kg SID)
- 0.8 mg/kg SQ q6hrs also reported in a recent case series of IMHA dogs – no bleeding complications noted
- Significant anti-Xa activity persists for > 12 hours. Maximum anti-Xa and anti-IIa activity 3-5 hrs post dose
- No consensus exists regarding continued dosing and tapering after discharge from the hospital. Consider reducing frequency to q24hrs for 7-10 days before stopping dosing at home