Heparin Bolus Dosing for Bridging Therapy in Severe MS
For patients with severe Multiple Sclerosis requiring bridging therapy during temporary discontinuation of acitrom, the recommended unfractionated heparin bolus dose is 60 U/kg (maximum 4000 U) followed by an initial infusion of 12 U/kg per hour (maximum 1000 U/hr) adjusted to maintain aPTT at 1.5 to 2.0 times control (approximately 50 to 70 seconds). 1
Dosing Protocol for Bridging Therapy
Initial Bolus and Infusion
- Bolus dose: 60 U/kg IV (not to exceed 4000 U)
- Initial infusion rate: 12 U/kg/hour (not to exceed 1000 U/hour)
- Target aPTT: 1.5-2.0 times control value (approximately 50-70 seconds)
Monitoring and Dose Adjustments
Monitor aPTT regularly and adjust the infusion rate according to the following guidelines:
| aPTT (seconds) | aPTT (× control) | Action |
|---|---|---|
| <35 | <1.2 | 80 units/kg bolus; increase infusion rate by 4 units/kg/hour |
| 35-45 | 1.2-1.5 | 40 units/kg bolus; increase infusion rate by 2 units/kg/hour |
| 46-70 | 1.5-2.3 | No change (therapeutic range) |
| 71-90 | 2.3-3.0 | Reduce infusion rate by 2 units/kg/hour |
| >90 | >3.0 | Stop infusion for 1 hour, then reduce rate by 3 units/kg/hour |
Evidence and Rationale
The American College of Cardiology/American Heart Association guidelines recommend weight-adjusted dosing for unfractionated heparin (UFH) when used for bridging therapy 1. This approach is supported by evidence showing that the predominant variable mediating the effect of heparin is weight, making weight-adjusted dosing crucial for achieving therapeutic anticoagulation quickly and safely.
When UFH is administered without fibrinolytics (as in bridging therapy), the recommended weight-adjusted dose is 60-70 U/kg IV bolus followed by 12-15 U/kg per hour infusion 1. This dosing regimen helps achieve therapeutic anticoagulation more rapidly than non-weight-adjusted protocols.
Special Considerations for MS Patients
Patients with severe Multiple Sclerosis may have additional risk factors that require careful monitoring:
- Immobility: MS patients often have reduced mobility, increasing their baseline risk for venous thromboembolism
- Steroid use: Many MS patients receive corticosteroids, which may further increase thrombotic risk
- Bleeding risk: Monitor for potential bleeding complications, especially if the patient has a history of falls
Timing of Bridging Therapy
When bridging from acitrom (acetylsalicylic acid):
- Begin heparin when the INR falls below the therapeutic range
- Continue heparin until the INR returns to the therapeutic range for at least 24 hours after resuming acitrom
Monitoring Requirements
- Check platelet counts daily to monitor for heparin-induced thrombocytopenia (HIT), particularly between days 4-14 of therapy 2
- Monitor aPTT every 6 hours initially until stable, then daily
- Assess for signs of bleeding or thrombosis
Potential Complications and Management
- Bleeding: If significant bleeding occurs, discontinue heparin and consider protamine sulfate (1 mg per 100 units of heparin given in the previous 2-3 hours)
- Heparin-induced thrombocytopenia: If platelet count drops by >50% or to <100,000/μL, discontinue heparin immediately
- Subtherapeutic anticoagulation: Research shows that patients who receive a bolus at initiation of therapy achieve therapeutic anticoagulation sooner than those without a bolus (9.6 vs 14.5 hours) 3
The evidence clearly supports the use of weight-adjusted bolus dosing for initiating heparin therapy, as it provides more predictable anticoagulation and faster achievement of therapeutic levels without increasing bleeding risk 3, 4.