Is citrate theophylline adenosine dipyridamole (CTAD) better than citrate to survey unfractionated heparin treatment? Has delayed centrifugation a real impact on this survey?

Abstract

Unfractionated heparin (UFH) is the main anticoagulant used in intensive care unit. The anticoagulant effect is monitored by activated partial thrombin time (aPTT) and anti-Xa activity (anti-Xa) measurement. However, delayed centrifugation induces platelet factor 4 (PF4) release and anti-Xa decrease. Several studies have concluded that aPTT and anti-Xa measurement should be performed within 2h in citrated anticoagulant but may be delayed longer in Citrate Theophylline Adenosine and Dypiridamol (CTAD) anticoagulant. The objective of this study was to compare the stability of both aPTT and anti-Xa in citrate and CTAD samples, and to determine the effect of delayed centrifugation on both aPTT, anti-Xa results, and PF4 release in citrate samples only. aPTT and anti-Xa were measured in citrate and CTAD anticoagulant samples from 93 patients. Delayed centrifugation was performed in citrate samples from 31 additional patients, with hourly aPTT and anti-Xa measurement from 1 to 6h. In 14 of these last patients, PF4 release was also evaluated with Human CXCL4/PF4 Quantikine ELISA Kit. We observed a significant correlation between citrate and CTAD anticoagulant for aPTT (r2 = 0.94) and anti-Xa (r2 = 0.95). With Bland-Altman correlation, a minor bias was observed for anti-Xa (- 0.025 ± 0.041). Delayed centrifugation in citrated anticoagulant showed an excellent concordance from 1 to 4h for aPTT (- 4.0 ± 5.3s) and anti-Xa (1.10-9 ± 0.058UI/ml) measurements. Moreover, PF4 release was not different between 1h (31.5 ± 14.7ng/ml) and 4h (33.8 ± 11.8ng/ml). We have demonstrated that anti-Xa measurement for unfractionated heparin should be done 4h in citrated plasma and that CTAD was not better than citrate. However, these initial findings require confirmation using other aPTT and calibrated anti-Xa assays.