The Use of the Point of Care in Evaluating the Anticoagulation Effect of Low Molecular Weight Heparin Nadroparin during Hemodialysis.
Authors: Berruyer Micheline , El Rouby Soumaya , Durbin Seta , Ffrench Patrick , Galland Philippe , Leitienne Philippe 
Published: October 2019

Abstract
Anticoagulation in hemodialysis is targeted to prevent the activation of coagulation during the procedure. Although unfractionated heparin (UFH) is the anticoagulant commonly used, recent studies suggested the safety and efficacy of low-molecular-weight heparin (LMWH) and possibly the most cost-effective anticoagulation for hemodialysis. The activated clotting time is usually used to monitor UFH while the chromogenic anti-Xa is the standard monitoring test for LMWH. The anti-Xa is not readily available; a bedside test may be helpful to ensure optimal anticoagulation. The objective of this study was to evaluate the utility of a whole blood (WB) point of care (POC) test, HEMONOX™ (HEMOCHRON Signature+) in measuring the anticoagulation effect of Nadroparin (FRAXIPARINE®, Sanofi, France) in normal blood samples spiked with different concentrations of Nadroparin and in clinical samples from patients during hemodialysis. Following IRB approval, Nadroparin was administered to the patients (n=11) at 56 IU/Kg 3–4 min before dialysis as a single bolus dose injected into the arterial needle pre-dialysis. Blood samples were obtained at baseline, 15 min and 2 hrs post bolus and at the end of the hemodialysis for performing the following POC tests: HEMONOX, low range activated clotting time (ACT-LR) and WB-activated partial thromboplastin time (WB-aPTT). Plasma samples were separated from each blood draw for the determination of the laboratory plasma based aPTT test (Lab-aPTT, Biomerieux France) and the anti-Xa assay (STAGO, France). In vitro analyses were performed by adding Nadroparin at increasing concentrations to fresh WB from 4 healthy donors. These samples were tested for clotting time using WB-aPTT, ACT-LR and HEMONOX. All WB-POC tests showed a linear dose response to Nadroparin in concentrations of 0–2.5 IU/ml and the overall clotting time results suggest variable levels of sensitivity to Nadroparin. The HEMONOX assay showed more sensitivity to the Nadroparin concentration with increases of 2–6 fold from baseline at LMWH levels of 1 and 1.5 IU/ml blood, compared to 1.2–1.5 and 1.5–3.0 fold for the ACT-LR and the WB-aPTT respectively. The clinical data confirmed these results and also correlated well to the anti-Xa activity levels. HEMONOX values obtained at baseline time (72–109 seconds) corresponded to undetectable anti-Xa. HEMONOX peak values obtained at 15 min post bolus, corresponded to therapeutic anti-Xa level but patients showed variable response to Nadroparin. HEMONOX clotting time (CT) at peak response suggested 3 patient subgroups with different levels of sensitivity to Nadroparin: low (range: CT 92–98 seconds and anti-Xa 0.56–1.0 U/ml), intermediate (range: CT 123–160 seconds and anti-Xa 0.90–1.37 U/ml) and high responders (range: CT 319–870 seconds and anti-Xa 1.2–1.30 U/ml). The HEMONOX test was the most sensitive indicator of Nadroparin anticoagulation when compared to POCT ACT-LR and WB-aPTT coagulation tests. The HEMONOX method showed a good correlation to the Lab-aPTT (r= 0.86, n= 36) and both methods yielded comparable correlation coefficient to anti-Xa (r= 0.71, n= 27). The results from this pilot study suggest that the WB-POC test HEMONOX is sensitive to the anticoagulant effect of Nadroparin during hemodialysis. More studies are needed to confirm the significance of these findings.