What is the recommended dose of heparin (unfractionated heparin) for Deep Vein Thrombosis (DVT) prophylaxis?

Recommended Dose of Unfractionated Heparin for DVT Prophylaxis

For DVT prophylaxis, administer unfractionated heparin 5000 units subcutaneously every 8 hours, as this regimen provides superior efficacy compared to twice-daily dosing while maintaining an acceptable safety profile. 1, 2, 3, 4

Standard Prophylactic Dosing

The established prophylactic dose is 5000 units subcutaneously every 8 hours (three times daily). 1, 2, 3, 4 This recommendation is based on multiple American Heart Association guidelines and is specifically endorsed for:

• General medical patients requiring DVT prophylaxis 1
• Surgical patients undergoing non-orthopedic procedures 1
• Cancer patients requiring thromboprophylaxis 2, 3, 4
• Patients with acute ischemic stroke 1

The three-times-daily regimen provides more consistent anticoagulant effect throughout the 24-hour period compared to twice-daily administration. 3, 4, 5

Evidence Supporting Three Times Daily Over Twice Daily Dosing

Three times daily dosing (5000 units every 8 hours) is more effective than twice daily dosing (5000 units every 12 hours) for preventing clinically significant VTE events. 2, 4, 5, 6

• A meta-analysis demonstrated that three times daily dosing showed a trend toward reduction in the combined endpoint of proximal DVT and PE (p = 0.05) 4, 6
• The relative risk for DVT prevention was 0.28 (95% CI 0.21-0.38) with three times daily dosing versus 0.4 (95% CI 0.22-0.73) with twice daily dosing when compared to placebo 5
• In general surgery patients, three times daily dosing was specifically shown to be more effective than twice-daily administration 2, 4

The trade-off is a higher bleeding risk with three times daily dosing (0.96 vs 0.35 per 1,000 patient-days, p < 0.001), though major bleeding remains uncommon overall. 4, 6 For patients at very high bleeding risk, twice-daily dosing (5000 units every 12 hours) may be considered as an alternative, accepting somewhat reduced efficacy. 4, 6

Timing and Duration

Initiate heparin prophylaxis:

• Within 12 hours of hospital admission for medical patients 7
• 2 hours before surgery for surgical patients 3

Continue prophylaxis:

• Until the patient is fully ambulatory or hospital discharge for medical patients 2, 3
• For at least 7-10 days postoperatively for surgical patients 2, 3, 4
• Throughout hospitalization for acutely ill medical patients 1

Special Population Adjustments

Renal Impairment

UFH is the preferred agent for patients with severe renal insufficiency (creatinine clearance <30 mL/min). 2, 3, 4 No dose adjustment is required because UFH is primarily metabolized by the liver rather than renally excreted. 2, 3, 4 The standard dose of 5000 units every 8 hours can be used safely. 3, 4

Cancer Patients

For cancer patients, UFH 5000 units subcutaneously every 8 hours is the specifically recommended regimen. 2, 3, 4 This population may benefit from extended prophylaxis duration, especially with ongoing risk factors. 2

Obesity

For obese patients (BMI >30 kg/m²), consider alternative agents such as enoxaparin with intermediate or weight-based dosing rather than increasing UFH doses, as UFH dosing adjustments for obesity are not well-established. 2

Critical Pitfalls to Avoid

Do not confuse prophylactic with therapeutic dosing. 3, 4 Therapeutic UFH requires weight-based dosing (80 units/kg bolus followed by 18 units/kg/hour infusion) with aPTT monitoring to maintain levels 1.5-2.5 times control. 1 Prophylactic dosing uses fixed doses without monitoring.

Avoid administering heparin too close to neuraxial anesthesia. 2, 3, 4 This significantly increases the risk of spinal hematoma. Ensure appropriate timing intervals between heparin administration and spinal/epidural procedures.

Monitor platelet counts every 2-3 days from day 4 to day 14 in patients at risk for heparin-induced thrombocytopenia (HIT). 4 Do not use UFH in patients with active or history of HIT; use a direct thrombin inhibitor or fondaparinux instead. 4

Do not routinely monitor anti-Xa levels or aPTT for prophylactic dosing. 2, 4 Monitoring is unnecessary for standard prophylaxis and adds no clinical benefit.

Injection site bruising occurs in approximately 20% of patients but is not a contraindication to continuing therapy. 7 True bleeding complications requiring transfusion are rare (0.35-0.96 per 1,000 patient-days). 4, 6

When UFH is Preferred Over LMWH

Choose UFH over low molecular weight heparin in these specific situations:

• Severe renal impairment (CrCl <30 mL/min) 2, 3, 4
• Need for rapid reversibility with protamine 3, 4
• History of HIT where fondaparinux is unavailable 4
• Cost constraints or lack of access to LMWH 3

Otherwise, LMWH (enoxaparin 40 mg daily or dalteparin 5000 units daily) is generally preferred over UFH when renal function is normal due to more predictable pharmacokinetics, once-daily dosing, and lower rates of HIT. 1, 2, 4