Protocolled Redefinition of the Therapeutic Range for Unfractionated Heparin: Lost in Translation?

Background: Protocolled treatment with unfractionated heparin (UFH) is a subject of ongoing debate. Even though international guidelines prescribe calibration of the activated partial thromboplastin time (aPTT) to 0.3 to 0.7 U/mL anti-Xa activity to establish an UFH therapeutic range, evidence for this approach remains scarce. In this study, we evaluated different strategies to delineate the UFH therapeutic range and analyzed the effects on patient therapeutic classification. Methods: In 109 patient samples, the aPTT was measured with 2 different reagents, both of which used mechanical clot detection. The UFH therapeutic range was determined using 3 previously described methods: calibration of the aPTT to 0.3 to 0.7 U/mL anti-Xa activity, application of 1.5 to 2.5 times the control aPTT, or using 0.3 to 0.7 U/mL anti-Xa activity directly. We also applied the UFH therapeutic range of a second hospital to our patient population. Results: Application of the guideline-prescribed anti-Xa calibration method would result in patients receiving increased UFH dosage in comparison to our previous UFH nomogram. Between-method and between-laboratory variations in aPTT and anti-Xa activity assays are a likely cause of these discrepancies. Additionally, we show that individual patient characteristics, such as weight and UFH treatment duration, likely contribute to the discordance between different strategies to establish an UFH therapeutic range. Conclusion: No consensus is reached between different strategies to define the UFH therapeutic range, which could result in relevant differences in UFH doses applied in patients. Clinicians and laboratory specialists should critically evaluate UFH monitoring protocols and be aware of their shortcomings.