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

• Published in: Journal of thrombosis and thrombolysis 2019-08, Vol.48 (2), p.277-283
• Main Authors: Billoir, Paul, Clavier, Thomas, Guilbert, Arnaud, Barbay, Virginie, Chrétien, Marie Hélène, Fresel, Marielle, Abriou, Caroline, Girault, Christophe, Le Cam Duchez, Véronique
• Format: Article
• Language: English
• Subjects: Adenosine; Anticoagulants; Anticoagulants - pharmacology; Blood Coagulation Tests; Blood Preservation - methods; Cardiology; Centrifugation; Citrates - pharmacology; Citric acid; Dipyridamole; Dipyridamole - pharmacology; Drug Monitoring - methods; Enzyme-linked immunosorbent assay; Hematology; Heparin; Heparin - pharmacokinetics; Heparin - therapeutic use; Humans; Medicine; Medicine & Public Health; Phosphodiesterase Inhibitors - pharmacology; Platelet factor 4; Theophylline; Thrombin; Time Factors
• ISSN: 0929-5305; 1573-742X
• DOI: 10.1007/s11239-019-01882-1

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 2 h 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 6 h. 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 (r 2  = 0.94) and anti-Xa (r 2  = 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 4 h for aPTT (− 4.0 ± 5.3 s) and anti-Xa (1.10 −9  ± 0.058 UI/ml) measurements. Moreover, PF4 release was not different between 1 h (31.5 ± 14.7 ng/ml) and 4 h (33.8 ± 11.8 ng/ml). We have demonstrated that anti-Xa measurement for unfractionated heparin should be done 4 h 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.