Evaluation of a new protamine titration method to assay heparin in whole blood and plasma

When unfractionated heparin is used for therapeutic anticoagulation, the heparin effect must be monitored to avoid thrombotic or hemorrhagic complications. The ability of a factor Xa inhibition (XaI) assay was compared with that of a low-level heparin protamine titration (LLHPT) assay to measure the concentration of heparin after heparin was added in vitro to specimens of plasma and whole blood. Heparin effect on the activated partial thromboplastin time also was assessed in the same specimens. The XaI and LLHPT assays had comparable precision and provided linear results over a wide range of heparin concentrations. Both assays slightly underestimated the total amount of heparin added to the specimens. The most rapid test was the whole blood LLHPT assay; this test therefore may be useful for bedside monitoring of heparin. A significant disadvantage of the LLHPT assay was the large sample size required to perform it. These results provide in vitro evidence that the XaI and LLHPT assays can provide equally precise monitoring of heparin concentration.