Warfarin binding to plasma albumin, measured in patients and related to fatty acid concentrations

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Abstract
A method for determination of reserve albumin equivalent for binding of warfarin as previously described [1] has been used for assessing the influence of non‐esterified fatty acid concentration (NEFA) on binding of warfarin to human serum albumin (HSA). Reserve albumin concentration can be used for calculation of the expected fraction of bound warfarin in serum. It is shown in vitro that binding of warfarin increases with added oleate up to 4 mol of oleate per mol of albumin and then decreases. Twenty‐four patients on permanent warfarin treatment showed no correlation of serum albumin and reserve albumin concentrations (r=0·10, P>0·50) indicating that warfarin binding is governed by other factors. However, in the same patients there was a significant correlation between reserve albumin concentration and NEFA/HSA (r= 0·54, P < 0·01). In one human volunteer changes of NEFA were provoked by strenuous work and it was found that reserve albumin concentration increased with NEFA concentration as expected from the in vitro findings (r= 0·90, P< 0·001). Five uraemic patients on permanent warfarin treatment showed increasing reserve albumin concentration with increasing NEFA concentration induced by heparin. These findings indicate that, both in vitro and in vivo, the reserve albumin concentration for binding of warfarin and hence the free warfarin concentration is markedly influenced by NEFA concentration. This may add to the understanding of warfarin dose requirement during anticoagulant therapy.