Jodie M. Fink

Differences in Warfarin Dosing Decisions Based on International Normalized Ratio Measurements with Two Point‐of‐Care Testing Devices and a Reference Laboratory Measurement

Study Objectives. To assess the accuracy of warfarin dosing decisions and the degree of numeric bias between two point‐of‐care devices using a local reference laboratorys international normalized ratio (INR) as the standard measure, and to determine the relationship between dosing decisions and INR values obtained with the pointof‐care devices.

Low-Dose 3-Factor Prothrombin Complex Concentrate for Warfarin Reversal Prior to Heart Transplant

Background: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. Objective: To assess blood product use, effectiveness, and safety post–low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. Methods: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio ≥1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. Results: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. Conclusions: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non–statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

Alteplase for central catheter clearance: 1 mg/mL versus 2 mg/2 mL

TO THE EDITOR: Tissue plasminogen activator (alteplase) has emerged as the agent of choice for catheter clearance.1 The most commonly studied and used dose is 2 mg/2 mL,1-4 yet such a dose may exceed the actual volume of the catheter, wasting potentially half of the dose. Since the priming volume of many central venous catheters is approximately 1 mL, and because the standard concentration of alteplase is 1 mg/mL, we hypothesize that using alteplase 1 mg/mL is as effective as 2 mg/2 mL for catheter clearance. This report describes the study we performed to establish the clinical equivalence of alteplase 1 mg/mL versus 2 mg/2 mL for catheter clearance. Methods. This randomized, unblinded trial enrolled adults with catheter occlusions. Single-, double-, or triple-lumen tunneled catheters or implanted ports were included. Occlusions were defined as the inability to infuse into or withdraw from the catheter. Patients were randomized to receive alteplase 1 mg/mL or 2 mg/2 mL (Figure 1). The doses were aliquoted from 50-mg vials of alteplase and frozen until time of use.1 In the event a patient had >1 occluded lumen, the same dose was administered to each occluded lumen. Data were analyzed using Blackwelder’s method.5 We considered doses to be equivalent if the clearance rates were within 10% of each other. Treatments were considered equivalent if the 95% CI of the difference in lumen clearance rates between treatment groups was between –10% and 10%. With an α level of 0.05, 226 lumens were needed to ensure 80% statistical power to demonstrate equivalence according to our a priori criteria. Results. Patients were enrolled between May 2001 and May 2002; however, due to lower than expected subject accrual, the study was stopped before the target 226 lumens were enrolled. A total of 61 lumens in 45 patients were enrolled. One-third of the lumens were implanted ports and the other two-thirds were tunneled catheters. All catheters fit the criteria due to the inability to withdraw, whereas 43% of the lumens had dysfunction described as both inability to infuse and withdraw. Thirty-seven lumens were randomized to receive alteplase 1 mg/mL. Clearance rates after one dose of alteplase 1 mg/mL versus 2 mg/2 mL were 81.1% and 83.3%, respectively (% difference –2.3%; 95% CI –18.7% to 14.1%). Similarly, clearance rates after 1 or 2 doses were 85.5% for alteplase 1 mg/mL and 87.5% for alteplase 2 mg/2 mL (% difference –1.0%; 95% CI –15.5% to 13.4%). No adverse events were reported in either group during the study. Numerous studies have examined the use of alteplase for catheter clearance. Our study offers advantages over previous literature in that it was a randomized trial examining 2 doses of alteplase in central venous catheters. Although the statistical criteria for equivalence were not reached, the clearance rates for the different doses of alteplase were similar. Therefore, since the 2 mg/2 mL dose is greater than the priming volume of the catheter, it appears reasonable to use alteplase 1 mg/mL as an initial dose for clearing central venous catheter occlusions.

Validity of Criteria Used to Evaluate Fingerstick Devices That Assess International Normalized Ratio

Background . Investigators commonly rely on unvalidated, mainly arithmetic criteria to predict if point-of-care fingerstick devices that assess International Normalized Ratio (INR) lead to the same warfarin dosing decisions as a standard measure. Methods . Criteria that predict warfarin dosing agreement between 2 INR measurements were evaluated using clinicians’ actual dosing decisions as the standard. Bayesian hierarchical modeling was used to rank the criteria by the proportion of correct dosing predictions and the magnitude of difference between actual and predicted dosing agreement. Results . The prediction criteria misclassified dosing agreement for between 19% and 38% of paired INR values (x̄x: 27%). The magnitude of misclassification varied inconsistently throughout the INR scale. Conclusion . The unvalidated criteria used to predict warfarin dosing agreement between 2 INR measurements are associated with large error. Warfarin dosing decisions should be measured directly in such assessments.