Heparin..Part II..Heparin Resistance

Heparin resistance is defined in terms of the context: A) in treatment of VTE, if more than 35,000 u / 24 hour period is required to prolong the aPTT to the therapeutic range, or B) in cardiac bypass surgery, if after heparinization, there is at least one ACT greater than 400 s or if exogenous antithrombin is required.


In general, studies have sited heparin resistance to occur due to a multitude of factors in 22% of patients undergoing major surgery. 
AT deficiency only accounts for one possible cause among many including increased clearance of heparin from the plasma, elevations of various heparin binding proteins (as mentioned above), elevations in FVIII and fibrinogen levels.  Medications such as aprotinin and nitroglycerin have also been sited as causal of heparin resistance.  
In patients previously exposed to heparin or requiring an IABP,  resistance may arise.  In the surgical population it is likely that when resistance to heparin occurs, it is due to decreased AT activity. 


Lemmer JH et al  found 85% of patients to have low AT activity, while another group noted the rate to be 77%  of those who were heparin resistant.  Both of these authors reported that  AT concentrate was able to prolong the ACT to the target range in patients found to have below normal AT activity who did not initially achieve the target ACT.