A-398 A Whole Blood Clotting Time (WBCT) test with Sensitivity to Warfarin Anticoagulation

Abstract Background The Perosphere ClotChek™ system (ClotChek) is a novel point of care test (POCT) which measures a highly sensitive and precise Whole Blood Clotting Time (WBCT) with demonstrable sensitivity to the Direct Oral Anticoagulants (DOACs), Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH). The WBCT uses a unique laser-etched glass cuvette, the surface of which induces a “contact activation” of the intrinsic coagulation cascade to initiate clot formation, thus achieving a level of sensitivity necessary for measurement of the moderate anticoagulant effects observed with low concentrations of these agents. Based on the unique sensitivity of the WBCT to the vitamin K derived clotting factors contributing to the intrinsic pathway, it was postulated that the ClotChek may also be sensitive to vitamin K antagonist (VKA) anticoagulation related to warfarin, a commonly used oral anticoagulant. Methods Whole blood samples obtained via fresh venipuncture from nine (Informed Consent) patients receiving therapeutic warfarin therapy were collected using a two-syringe technique to ensure no tissue thromboplastin contamination was present in the blood collection tube(s). An initial 5 cc sample was collected and discarded, followed by a second blood sample collected in a non-additive, plastic vacutainer tube (Z top, BD) for the ClotChek test (2 replicates) and the Roche PT/INR (2 replicates) and a second sample in 3.2% sodium citrate for the purpose of performing a laboratory PT/INR (Sysmex, 2 replicates). The POCT PT/INR and lab PT/INR served as the confirmation of the donor’s anticoagulated state. The warfarin dose across these donors varied from 2.5 mg to 25 mg daily dose, thus providing a full spectrum of therapeutic INR response. Results The individual comparative results for each VKA donor are shown in the table 1 in ascending order of INR value. The mean INR for the VKA population (2.56 ± 0.35) is consistent with an acceptable anticoagulation range for the patient’s prescribed dose of warfarin. Correspondently, the mean ClotChek WBCT value (357.28 ± 46.76) is elevated above the normal reference range of 200 to 290 seconds. For each individual donor, the WBCT > 290s is reflective of an anticoagulated state corresponding to the elevated INR. Conclusion This preliminary evaluation demonstrates the sensitivity of the ClotChek WBCT to VKA anticoagulation for patients that are adequately anticoagulated to achieve an appropriate therapeutic INR. While sensitivity to lower levels of VKA anticoagulation has yet to be established; this limited pilot study offers the potential for the ClotChek as a universal high sensitivity whole blood assay for detection of meaningful VKA anticoagulation in specific situations where a PT/INR test may not be readily available or as an accompaniment to the use of the ClotChek WBCT in DOAC anticoagulation.