What is the appropriate dosing of Clexane (enoxaparin) for venous thromboembolism prophylaxis and treatment, including adjustments for renal impairment, low body weight, and pregnancy?

Enoxaparin (Clexane) Dosing Guidelines

Standard Prophylactic Dosing

For hospitalized medical or surgical patients, administer enoxaparin 40 mg subcutaneously once daily for the duration of hospital stay or until fully ambulatory. 1

• For surgical patients undergoing major abdominal or pelvic cancer surgery, continue prophylaxis for up to 30 days postoperatively, as this reduces VTE risk by 60% without increasing bleeding 2
• Prophylaxis should be continued for at least 7-10 days in surgical patients, with extended prophylaxis up to 4 weeks for high-risk cases 1

Surgical Timing Options

• Option 1: 40 mg administered 10-12 hours preoperatively, then 40 mg once daily thereafter 1
• Option 2: 20 mg administered 2-4 hours preoperatively, then 40 mg once daily thereafter 1

Therapeutic Dosing for VTE Treatment

For treatment of established deep vein thrombosis or pulmonary embolism, use enoxaparin 1 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg subcutaneously once daily. 1, 2

• Initial treatment typically lasts 5-10 days 1, 2
• For cancer-associated VTE, continue enoxaparin for at least 6 months, and indefinitely while cancer remains active or under treatment 1, 2
• After the first month of cancer treatment, consider dose reduction to 75-80% of initial dose (e.g., dalteparin reduced from 200 to 150 units/kg daily in the CLOT study) 2

Critical Dose Adjustments for Renal Impairment

In patients with severe renal impairment (creatinine clearance <30 mL/min), mandatory dose reduction is required due to 44% reduction in enoxaparin clearance and 2-3 fold increased bleeding risk. 2, 3, 4

Renal Dosing Algorithm

• Prophylactic dose: Reduce to 30 mg subcutaneously once daily 1, 2, 3
• Therapeutic dose: Reduce to 1 mg/kg subcutaneously once every 24 hours (instead of every 12 hours) 1, 2, 3
• Moderate renal impairment (CrCl 30-50 mL/min): Enoxaparin clearance decreases by 31%; consider dose reduction to 0.8 mg/kg every 12 hours after the first full dose 2, 3

Anti-Xa Monitoring in Renal Impairment

• Monitor anti-Xa levels in patients with CrCl <30 mL/min receiving prolonged therapy 1, 2, 3
• Target range: 0.5-1.5 IU/mL for therapeutic dosing 2, 3
• Draw levels 4-6 hours after dosing, after 3-4 consecutive doses have been administered 1, 2

Obesity-Specific Dosing

For patients with class III obesity (BMI ≥40 kg/m² or weight >120 kg), use weight-based prophylaxis of 0.5 mg/kg subcutaneously every 12 hours OR 40 mg every 12 hours. 2

• Weight-based prophylaxis (0.5 mg/kg q12h) more reliably achieves target anti-Xa levels (0.2-0.5 IU/mL) than fixed-dose regimens 2
• For therapeutic dosing in obesity (BMI ≥40 kg/m²), use 0.8 mg/kg subcutaneously every 12 hours 2
• Consider anti-Xa monitoring in morbidly obese patients to confirm target prophylactic ranges 2

Pregnancy Dosing

Standard prophylaxis in pregnancy is 40 mg subcutaneously once daily. 2

• For pregnant patients with class III obesity, use intermediate dosing of 40 mg every 12 hours OR 0.5 mg/kg every 12 hours 1, 2
• Pregnant patients receiving therapeutic-intensity enoxaparin should have anti-Xa levels monitored 2

Neuraxial Anesthesia Timing

Critical timing requirements to prevent spinal hematoma:

• Prophylactic dose (40 mg daily): May be started ≥4 hours after catheter removal but no earlier than 12 hours after the neuraxial block 2
• Intermediate or therapeutic doses (40 mg q12h): May be started ≥4 hours after catheter removal but no earlier than 24 hours after the block 2
• Do not administer prophylactic doses within 10-12 hours before neuraxial procedures or catheter removal 1, 2

Elderly Patients with Acute Coronary Syndrome

For patients aged ≥75 years with STEMI receiving fibrinolysis, omit the initial IV bolus and use a reduced dose of 0.75 mg/kg subcutaneously every 12 hours, not exceeding 75 mg per dose. 2

• For ACS patients aged ≥75 years, use 0.75 mg/kg subcutaneously every 12 hours without IV bolus (regardless of renal function) 3
• For ACS patients aged <75 years with CrCl <30 mL/min, use 1 mg/kg subcutaneously once daily (no IV bolus) 3

Post-Thrombolysis Timing

After IV alteplase for acute ischemic stroke, delay enoxaparin prophylaxis for at least 24 hours and start only after follow-up CT or MRI confirms no hemorrhagic transformation. 2

• Maintain systolic/diastolic blood pressure below 180/105 mm Hg throughout the first 24 hours 2
• Obtain follow-up imaging exactly 24 hours after alteplase before initiating any anticoagulant 2
• Never start enoxaparin before the 24-hour mark without imaging confirmation—doing so can cause catastrophic bleeding 2

Common Pitfalls and Critical Safety Points

Most Frequent Errors

• Failure to adjust dose for renal function: The most common error, leading to drug accumulation and increased bleeding risk 2, 3
• Not adjusting for obesity: Standard fixed dosing may be inadequate in obese patients and excessive in very low-weight patients 2
• Improper timing with neuraxial procedures: Can increase risk of spinal hematoma 2

Monitoring Requirements

• Monitor platelet counts every 2-3 days from day 4 to day 14 to screen for heparin-induced thrombocytopenia 2, 3
• If HIT is suspected, immediately discontinue all heparin products and switch to a non-heparin anticoagulant such as fondaparinux, argatroban, or a DOAC 2

Drug Interactions

• Avoid switching between enoxaparin and unfractionated heparin mid-treatment, as this increases bleeding risk 2, 3
• Do not add supplemental unfractionated heparin at the time of PCI in patients already on enoxaparin 3
• Use cautiously with other antiplatelet or anticoagulant medications due to increased bleeding risk 2

Alternative Agents in Severe Renal Impairment

• If concerns exist about VTE protection adequacy with reduced 30 mg dose, consider dalteparin 5000 IU daily (shows less bioaccumulation) or unfractionated heparin 5000 units subcutaneously every 8-12 hours (does not accumulate in renal failure) 3
• Avoid tinzaparin entirely in elderly patients (≥70 years) with renal insufficiency due to substantially higher mortality rates 2, 3