Point of Care Monitoring of the International Normalized Ratio in Patients with Antiphospholipid Antibodies.

Abstract Warfarin is effective in decreasing recurrent thrombosis in patients with antiphospholipid antibody syndrome (APS). Antiphospholipid antibodies (APAs) can influence the results of clotting tests in a subset of these patients, which can be a major obstacle in monitoring warfarin. In this study, 59 patients receiving warfarin for a diagnosis of APS were compared to 49 patients receiving warfarin for atrial fibrillation (AF) with regard to consistency between International Normalized Ratio (INR) results obtained from two Point of Care (POC) monitors and a standard plasma-based method used in the coagulation laboratory. INR results were obtained using a fingerstick for whole blood on the ProTime® monitor (International Technidyne Corp, ITC, Edison, NJ) and by venipuncture using both citrated and non-citrated whole-blood on a HEMOCHRON® Signature (Hr. Sig.) monitor (ITC). Parallel INR measurements were obtained on an MDA-180 analyzer (bioMerieux, Durham, NC), using Simplastin-HTF. Additional tests included chromogenic factor Xa (CFXa) and tests for APAs (antiphospholipid, anti-β2-glycoprotein I [β2GPI], and antiprothrombin ELISA's). Insufficient blood was obtained from 5 patients for testing with the ProTime® (3 AF, 2 APS). For an additional 5 patients, all with APS, sufficient blood was obtained, but an INR could not be determined by the instrument (8%). Single INR results on the ProTime® were obtained from 2 of these patients on repeat testing. The data were analyzed with the 100 patients who had at least one INR result with the ProTime®. Analyses included determination of the means of absolute differences between each method of obtaining INR results, correlations between INR results and CFXa results, and correlations with APAs results. Systematic differences were found for each INR method comparison, ranging from 0.24±0.23 to 0.41±0.29, with correlation coefficients ranging from 0.54 to 0.80. The differences were similar for AF and APS patients for all INR comparisons with the exception of the results comparing the standard plasma-based method with the ProTime®, which showed a mean absolute difference of 0.24 for AF patients and 0.39 for APS patients (p=0.01). Preliminary data analysis did not show perfect calibration between the CFXa and the different methods for obtaining INR results for either patient group. Correlation coefficients ranged from 0.3 to 0.7 when comparing CFXa to each INR method, and the best correlation was between the standard plasma INR and the CFXa for patients with AF (0.65). Review of testing for APAs at the time of INR testing revealed that 10 patients with AF had elevated antibody levels (20%; all by antiphospholipid ELISA only and most only minimally elevated), compared to 27 patients with APAs (45%, with 21 having elevated anti-β2 GPI antibody levels). The five patients with non-measurable ProTime® INRs had elevated anti-β2GPI levels and generally higher INRs with the Hr. Sig., but CFXa results were not supratherapeutic. In conclusion, these results suggest that in a subset of patients with APAs, the ProTime® will not yield any results and can not be used due to the internal QC set of the monitor. APA testing did not specifically identify which APS patients would most likely have problems with INR testing.