What is the initial dose and monitoring protocol for unfractionated heparin in a patient with DVT, considering factors such as weight, renal function, and history of bleeding disorders?

Unfractionated Heparin Dosing for DVT

For DVT treatment, initiate unfractionated heparin with an IV bolus of 80 units/kg followed by continuous infusion at 18 units/kg/hour, targeting an aPTT of 1.5-2.5 times control (typically 46-70 seconds). 1, 2, 3

Initial Dosing Protocol

Intravenous Administration (Preferred Route)

• Bolus dose: 80 units/kg IV push 1, 2, 3, 4
• Continuous infusion: 18 units/kg/hour 1, 2, 3, 4
• Target aPTT: 1.5-2.5 times control value (46-70 seconds), corresponding to anti-Xa levels of 0.3-0.7 IU/mL 1, 2, 3, 4

Subcutaneous Alternative (When IV Access Unavailable)

• Loading dose: 333 units/kg subcutaneously 1, 3, 4
• Maintenance: 250 units/kg subcutaneously every 12 hours 1, 3, 4

Critical point: Weight-based dosing is superior to fixed dosing and significantly reduces recurrent thromboembolism rates. 2 Fixed-dose protocols lead to higher recurrence rates and should be avoided. 2

Monitoring Protocol

Initial Monitoring

• First aPTT: Draw 6 hours after initiating therapy 3, 4
• Frequency: Check aPTT every 4-6 hours until therapeutic range achieved, then daily 3, 4
• Baseline labs: CBC, renal and hepatic function panel, aPTT, PT/INR before starting therapy 1

Ongoing Monitoring

• Platelet counts: Every 2-3 days from day 4 through day 14 to detect heparin-induced thrombocytopenia (HIT) 1, 2, 4
• Hemoglobin/hematocrit: Every 2-3 days for first 14 days, then every 2 weeks 1
• Occult blood in stool: Periodically throughout therapy 4

Dose Adjustment Nomogram

Adjust infusion rate based on aPTT results using this standardized protocol: 1, 3

• aPTT <35 seconds (<1.2× control): Give 80 units/kg bolus; increase infusion by 4 units/kg/hour 1, 3
• aPTT 35-45 seconds (1.2-1.5× control): Give 40 units/kg bolus; increase infusion by 2 units/kg/hour 1, 3
• aPTT 46-70 seconds (1.5-2.3× control): No change—therapeutic range 1, 3
• aPTT 71-90 seconds (2.3-3.0× control): Decrease infusion by 2 units/kg/hour 1, 3
• aPTT >90 seconds (>3.0× control): Stop infusion for 1 hour, then decrease by 3 units/kg/hour 1, 3

Achieving therapeutic aPTT within 24 hours is critical—delays increase mortality and recurrence rates. 2

Special Population Considerations

Renal Impairment

• Severe renal failure (CrCl <30 mL/min): Unfractionated heparin is the preferred anticoagulant over LMWH because it is primarily metabolized by the liver, not the kidneys 1, 2, 3
• No dose adjustment needed for renal dysfunction 1, 3

Morbidly Obese Patients

• Standard weight-based protocols with maximum dose caps cause significant delays in achieving therapeutic anticoagulation 5
• Use adjusted dosing weight: IBW + 0.3(ABW - IBW) or IBW + 0.4(ABW - IBW) 5
• Remove maximum dose restrictions from protocols for this population 5

Heparin Resistance

• Defined as requiring ≥35,000 units/day to achieve therapeutic aPTT 2
• Management: Switch to anti-Xa level monitoring (target 0.3-0.7 IU/mL) instead of aPTT 2

Bleeding Risk Factors

High-risk features include: 1

• Recent surgery or trauma 1
• Age >60 years 1
• Multiple comorbidities 1
• Supratherapeutic clotting times 1
• Worsening hepatic dysfunction 1

Absolute Contraindications

Do not use unfractionated heparin in: 1, 3, 4

• History of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis 1, 3, 4
• Known hypersensitivity to heparin or pork products 4
• Active uncontrolled bleeding (except DIC) 1, 4
• Central nervous system bleed or intracranial/spinal lesion at high risk for bleeding 1

Alternative anticoagulants for HIT: Use argatroban, bivalirudin, danaparoid, or fondaparinux instead 1, 3

When to Choose UFH Over LMWH

LMWH or fondaparinux is generally preferred for most DVT patients due to more predictable pharmacokinetics, no monitoring required, and lower HIT risk (up to 5% with UFH vs <1% with LMWH). 2

Specific indications for UFH: 1, 2, 3

• Severe renal impairment (CrCl <30 mL/min) 1, 2, 3
• Need for rapid reversibility with protamine (e.g., high bleeding risk, planned procedures) 2, 3
• Patients on continuous renal replacement therapy (CRRT) requiring anticoagulation 2
• Lack of reliable subcutaneous access 2
• Hemodynamically unstable patients where rapid titration is needed 2

Critical Pitfalls to Avoid

• Using fixed doses instead of weight-based dosing leads to higher recurrence rates 2
• Failing to achieve therapeutic aPTT within 24 hours increases mortality and recurrence 2
• Not validating your institution's aPTT reagent against anti-Xa levels—different reagents have variable heparin responsiveness, requiring laboratory-specific therapeutic ranges 2, 3
• Administering anticoagulants near neuraxial anesthesia risks catastrophic spinal hematoma 1, 2
• Not monitoring platelets from day 4-14 misses HIT, which occurs in up to 5% of patients 2, 4
• Ignoring warfarin's effect on aPTT—warfarin directly increases aPTT by approximately 20 seconds for each 1.0 increase in INR, potentially causing false supratherapeutic readings 6