Treatment of Heparin Resistance During Cardiopulmonary Bypass
When heparin resistance occurs during cardiopulmonary bypass (defined as failure to achieve ACT ≥480 seconds after 500 U/kg heparin), administer additional heparin boluses first, followed by antithrombin supplementation (either recombinant antithrombin or fresh frozen plasma) if additional heparin fails to achieve target ACT. 1
Stepwise Management Algorithm
Step 1: Administer Additional Heparin
- Give incremental heparin boluses (typically 5,000-10,000 units) and recheck ACT after each dose 2
- This addresses the most common scenario where initial dosing was simply insufficient
- The ACT target of ≥480 seconds should be achieved before initiating bypass 1
Step 2: Antithrombin Supplementation (If Additional Heparin Fails)
When additional heparin doses fail to achieve target ACT, antithrombin deficiency is the primary mechanism requiring treatment:
Option A: Recombinant Antithrombin (Preferred)
- Administer antithrombin concentrate to restore antithrombin levels 3, 2
- Critical caveat: Reduce heparin dosing when administering antithrombin, as the anticoagulant effect of heparin is significantly enhanced by concurrent antithrombin therapy, increasing bleeding risk 4
- Monitor ACT closely after antithrombin administration as the heparin effect will be potentiated 4
Option B: Fresh Frozen Plasma
- Administer 2-4 units of FFP to provide endogenous antithrombin 3, 2
- FFP is less specific than antithrombin concentrate but provides multiple coagulation factors
- Consider emerging safety concerns regarding FFP transfusion when making this choice 3
Step 3: Alternative Anticoagulation (Rare Circumstances)
- Bivalirudin can be used as adjunctive anticoagulation in refractory heparin resistance cases 5
- This is reserved for exceptional situations where standard approaches fail
Key Clinical Considerations
Monitoring Requirements
- Check ACT before initiating bypass and at regular intervals during the procedure 4
- Monitor platelet counts before and during heparin therapy to detect thrombocytopenia 4
- Consider anti-Factor Xa level monitoring in cases of suspected heparin resistance 4
Common Causes to Recognize
The FDA label identifies specific conditions associated with increased heparin resistance 4:
- Fever
- Active thrombosis or thrombophlebitis
- Infections with thrombosing tendencies
- Myocardial infarction
- Cancer
- Post-surgical state
- Antithrombin III deficiency (most important mechanism)
- Paraprotein disorders (IgM kappa can bind heparin and prevent antithrombin interaction) 6
Critical Safety Points
- Do not initiate bypass with inadequate anticoagulation, as this risks excessive hemostatic system activation and thrombotic complications 1
- The inability to achieve target ACT represents a genuine clinical concern requiring intervention before proceeding 2
- When antithrombin is administered, heparin dosing must be reduced to prevent excessive anticoagulation and bleeding 4
Important Nuance About ACT Targets
While the standardized definition uses ACT ≥480 seconds 1, historical data suggests that lower ACT values (even <400 seconds) may not necessarily increase bleeding or thrombotic complications 7. However, the current consensus supports the 480-second target for optimal safety during bypass 1.