Heparin: Recommended Use and Treatment Protocol
Primary Indications
Unfractionated heparin (UFH) is indicated for prophylaxis and treatment of venous thromboembolism, prevention of postoperative deep venous thrombosis, atrial fibrillation with embolization, acute coronary syndromes, and as anticoagulation during cardiac surgery and extracorporeal procedures. 1
The drug works by potentiating antithrombin III to inhibit thrombin (factor IIa) and factor Xa, preventing thrombus extension and new clot formation. 2
Treatment Dosing for Venous Thromboembolism (VTE)
Intravenous Administration (Preferred Route)
For acute VTE treatment, use weight-based dosing: 80 units/kg IV bolus followed by 18 units/kg/hour continuous infusion. 2 This regimen has been shown to significantly reduce recurrent thromboembolism compared to fixed-dose regimens. 2
Alternative non-weight-based dosing: 5,000 units IV bolus followed by at least 32,000 units/24 hours by continuous infusion. 2
Critical point: Achieving therapeutic aPTT within 24 hours is associated with lower in-hospital and 30-day mortality rates in pulmonary embolism patients. 2
Subcutaneous Administration (Alternative)
Two options exist for subcutaneous treatment of VTE:
- Option 1: 5,000 units IV bolus, then 250 units/kg subcutaneously twice daily 2
- Option 2: 333 units/kg subcutaneously initially, then 250 units/kg twice daily 2
Subcutaneous administration results in lower bioavailability and higher recurrence rates compared to IV infusion, so IV route is preferred when feasible. 2
Monitoring Requirements
Therapeutic Range
Target aPTT of 1.5 to 2.5 times the control value (or 60-85 seconds in pediatrics). 2, 1 However, the evidence supporting this specific range is weak, based only on retrospective analysis. 2
Monitoring Schedule
- For continuous IV infusion: Check baseline coagulation studies (aPTT, INR, platelet count), then aPTT approximately every 4 hours initially, then at appropriate intervals once stable 1
- For intermittent IV injection: Check coagulation tests before each injection during initiation 1
- For subcutaneous injection: Perform tests 4-6 hours after injection for optimal assessment 1
Platelet count monitoring is critical to detect heparin-induced thrombocytopenia (HIT). For patients with >1% HIT risk, monitor platelet counts every 2-3 days from day 4 to day 14 of therapy. 2, 3 For patients with <1% HIT risk, routine monitoring is not required. 2
Additionally, monitor hematocrit and stool occult blood throughout therapy regardless of administration route. 1
Acute Coronary Syndrome Dosing
Lower doses are used for ACS compared to VTE:
- Unstable angina/NSTEMI: 60-70 units/kg bolus (maximum 5,000 units) followed by 12-15 units/kg/hour infusion (maximum 1,000 units/hour) 2
- STEMI with fibrinolytics: 60 units/kg bolus (maximum 4,000 units) followed by 12 units/kg/hour (maximum 1,000 units/hour) 2
Prophylaxis Dosing
Low-Dose Prophylaxis for Postoperative Thromboembolism
Standard regimen: 5,000 units subcutaneously 2 hours before surgery, then 5,000 units every 8-12 hours for 7 days or until fully ambulatory, whichever is longer. 1 Administer by deep subcutaneous injection (above iliac crest or abdominal fat layer) using a 25-26 gauge needle. 1
For higher-risk patients (e.g., total hip replacement), use adjusted-dose subcutaneous heparin to prolong aPTT by 4-5 seconds into upper normal range. 4
Pediatric Dosing
Use preservative-free formulations in neonates and infants. 1
- Initial dose: 75-100 units/kg IV bolus over 10 minutes 1
- Maintenance infusion:
- Target: aPTT of 60-85 seconds (reflecting anti-Factor Xa level of 0.35-0.70) 1
Cardiovascular Surgery
For open-heart surgery with cardiopulmonary bypass: minimum 150 units/kg initial dose. 1 More commonly:
For urgent cardiac surgery in patients with acute HIT, bivalirudin is preferred over heparin. 2, 3
Heparin-Induced Thrombocytopenia (HIT) Management
Recognition and Immediate Action
If HIT is suspected (unexplained thrombocytopenia, new thrombosis, skin lesions, or acute systemic reactions), immediately discontinue ALL heparin products and initiate alternative nonheparin anticoagulation before laboratory confirmation. 2, 3
Alternative Anticoagulants
For HIT with normal renal function: use argatroban, lepirudin, or danaparoid. 2, 3
For HIT with renal insufficiency: argatroban is preferred. 2
For HIT patients requiring percutaneous coronary intervention: use bivalirudin (Grade 2B) or argatroban (Grade 2C). 2
Transitioning to Warfarin
Do not start warfarin until platelets recover to at least 150 × 10^9/L. 2, 3 When starting:
- Use low initial doses (maximum 5 mg warfarin) 2, 3
- Overlap with nonheparin anticoagulant for minimum 5 days and until INR is therapeutic 2, 3
- If warfarin already started when HIT diagnosed, administer vitamin K 2
Transitioning to Oral Anticoagulants
Converting to Warfarin
Continue full-dose heparin for several days until INR reaches stable therapeutic range, then discontinue heparin without tapering. 1 The overlap prevents the transient hypercoagulable state that occurs when warfarin is initiated. 1
Converting to Non-Warfarin Oral Anticoagulants
- For IV heparin: Stop infusion immediately after first dose of oral anticoagulant 1
- For intermittent IV heparin: Start oral anticoagulant 0-2 hours before next scheduled heparin dose 1
Bleeding Risk Factors and Management
Bleeding risk increases with:
- Higher heparin doses 2
- Concomitant fibrinolytics or glycoprotein IIb/IIIa inhibitors 2
- Recent surgery, trauma, or invasive procedures 2
- Age >60 years, multiple comorbidities, supratherapeutic clotting times, hepatic dysfunction 2
Avoid intramuscular injections due to high risk of hematoma formation. 1
For severe thrombocytopenia in HIT patients, give platelet transfusions only for active bleeding or high-risk invasive procedures. 2
Critical Pitfalls to Avoid
Medication errors: Confirm correct vial strength before administration—do not confuse treatment vials with catheter lock flush vials 1
Inadequate initial dosing: Failure to achieve therapeutic aPTT is associated with 25% risk of recurrent thromboembolism 2, 5
Delayed HIT recognition: Monitor platelets starting day 4 in at-risk patients; delayed recognition leads to devastating thrombotic complications 2, 3
Premature warfarin initiation in HIT: Starting warfarin before platelet recovery can cause venous limb gangrene 2, 3
Inadequate mixing of IV solutions: Invert container at least 6 times when adding heparin to prevent pooling 1