Drug Criteria and Outcomes-Whole-blood prothrombin time monitors
An evaluation in an anticoagulation clinic
By Rhonda M. Jones, PharmD
Craig A. Pedersen, RPh, PhD
School of Pharmacy and Allied Health
Creighton University
Omaha, NE
Introduction
Many patients with thromboembolic disorders are receiving warfarin anticoagulation therapy. Because of the risk of serious bleeding complications, careful prescribing, administration and monitoring procedures are essential. The currently preferred method of monitoring warfarin therapy is the International Normalized Ratio (INR). This test usually requires a venipuncture, which can be costly and time-consuming. The cost, as well as the possibility of lengthy waiting times at some institutions, can discourage patients from complying with frequent follow-up appointments.
In contrast, the Coumatrak protime test system provides immediate results by analyzing whole blood obtained by a fingerstick. In previous studies, this method has been shown to save money and time, as well as be accurate and useful for home prothrombin time monitoring. To determine the possible value of the Coumatrak system in assessing patients in our anticoagulation clinic, we conducted a study to compare this system with our institution's laboratory method.
Methods
Patients included in the study were receiving warfarin sodium (Coumadin) for long-term oral anticoagulation at a Department of Veterans Affairs ambulatory anticoagulation clinic; these patients had atrial fibrillation, cerebrovascular accidents, recurrent transient ischemic attacks, or mechanical valve replacement as the indications for their therapy. Thus, the goal of anticoagulation for all patients was an INR of 2 or 3, or 2.5 to 3.5, depending on the therapeutic indication.
Patients excluded from the study included those who were receiving warfarin for short- term anticoagulation (less than six months).
Paired testing, using the Coumatrak whole blood system and the hospital laboratory's plasma prothrombin time test, was completed for all patients who gave their verbal consent. Control samples for both the Coumatrak monitor and the hospital laboratory were tested daily.
The patients also were asked to complete a brief questionnaire comparing the Coumatrak procedure with the laboratory procedure with respect to pain, convenience, waiting time, and preference.
Coumatrak procedure
The Coumatrak protime test system is designed for use in the quantitative determination of the prothrombin time of freshly drawn whole blood. The test is initiated by inserting a reagent cartridge into the Coumatrak monitor. A monitor reads the code on the cartridge to determine test identity and calibration. The cartridge also contains a sample target area, a reagent chamber containing thromboplastin extracted from rabbit brain and a molded capillary path.
Another monitor heats the cartridge; a drop of fresh, whole blood (25mcL) is placed on the sample site of the reagent cartridge. Blood is drawn by capillary action into the reagent chamber, where it mixes with the thromboplastin to initiate the coagulation process. The blood sample is then drawn along the capillary path until a clot forms.
The monitor detects the time from application of blood to cessation of flow, converts this time to a laboratory plasma prothrombin time equivalent, and displays the results in seconds as a prothrombin time ratio and an INR. The control prothrombin time is 12.0 seconds; the Interna tional Sensitivity Index (ISI) is 2.04. Lot-to-lot variation in reagent reactivity is corrected electronically. Once the sample of blood is applied, the test is completed in about two minutes.
Hospital laboratory procedure
Hospital laboratory prothrombin times and INR values were obtained using the MLA Elector 800 Coagulyzer with Simplastin-L. The laboratory's mean control prothrombin time was 11.9 seconds, and the ISI was 2.79 for that particular lot number of rabbit thromboplastin. Control samples were tested every eight hours. Results are reported as prothrombin time in seconds and an INR.
Results
Sixty subjects were enrolled during the study period. Indications for anticoagulation included: atrial fibrillation, 38 (63%); cerebrovascular accident, 17 (28%); recurrent ischemic attacks, 5 (8%); and mechanical valve replacement, 0 (0%). INR values were collected for all 60 patients enrolled in the study.
Subjects arrived at the clinic and had venous blood drawn and a fingerstick for the Coumatrak test system performed. The two procedures occurred within a 60-minute period. Patients then were instructed to wait for the hospital lab test results before warfarin dose adjustments were made. The typical waiting time was one to two hours.
Both mean and standard deviations for the INR values were calculated for both the hospital lab and the Coumatrak protime test system. (See Table 1, p. 4.) When paired t-tests were performed on the data, the INRs from the hospital lab and the Coumatrak system differed significantly (p = 0.0001).
The INR values also were divided according to attainment of the therapeutic range (2-2). Of the 60 subjects enrolled in the study, 33 (55%) had hospital lab INR values outside of the therapeutic range, and 25 (42%) had Coumatrak values outside of the therapeutic range. These frequencies also differed significantly upon chi square analysis (x2 = 14.563, p = 0.0001). See Table 2, above, for a breakdown of INR values and data concerning attainment of the therapeutic range for the hospital lab and the Coumatrak procedures.
During waiting time, patients were asked to complete a questionnaire about the Coumatrak system, which requested information on pain, convenience, waiting time, and preference. Forty eight subjects (80%) completed the survey. Results are summarized in Table 3, p. 6.
The overwhelming majority of patients reported the same or less pain (91%), increased convenience (100%) and an equal or lesser amount of waiting time (100%) with the Coumatrak system. They also preferred the system (96%) over the hospital system.
Discussion
The findings indicate that INR results from the hospital and Coumatrak systems differ sig nificantly. The Coumatrak system produced INR values and standard deviations that were significantly lower than those from the hospital laboratory.
Possible reasons for the variability in INR values include use of low-sensitivity thromboplastin, difficulty with the fingerstick technique, and inaccuracy in manufacturer-determined ISI values. INR values obtained from the hospital laboratory may have been erroneously high because the hospital lab used a low-sensitivity thromboplastin (ISI = 2.79). Thus, the low-sensitivity thromboplastin could be the cause of the large differences found between the two systems. These results are similar to those found in other studies.
The data from our study and other studies are a concern, because different INR results suggest that different warfarin doses are needed to obtain a therapeutic INR value. The consequence of a therapeutic decision based on inaccurate data could be excessive bleeding or increased risk of thrombus formation. Due to these concerns, there have been recent recommendations that laboratories use thromboplastins with high sensitivity (low ISI values) for prothrombin time and INR value monitoring.
Patients clearly prefer the Coumatrak system, which may be directly related to the Veterans Affairs integrated health care system, in which patients must have all of their care provided at a VA site for costs to be covered. Thus, patients often make long trips from distant parts of the state or surrounding states and then must wait for the results of lab tests before warfarin adjustments are made.
Limitations of the study included possible bias of data, since all patients being monitored were enrolled in the study rather than random selection. In addition, a fairly small number of patients (60) were evaluated.
Conclusion
Our data add to previous evidence that there can be significant differences between INR values obtained through the hospital laboratory and the Coumatrak system, if a low-sensitivity thromboplastin is used. Pharmacists practicing in out-patient settings who are monitoring anticoagu- lation patients should keep in mind that findings from the portable prothrombin time monitor may correlate better with lab values if high sensitivity thromboplastin is used.
The clinician should not assume that the INR normalizes prothrombin time results obtained with different thromboplastins. Thus, the pharmacist who is using or who may be considering widespread use of a portable system should check the ISI value of the lab and encourage the use of a high-sensitivity thromboplastin.
Several portable blood-monitoring devices are now available. These devices may assist pharmacists in providing care to patients. However, guidelines pertaining to the appropriate use of these devices are essential to decrease erroneous variability in patient data.
Author's note: Since the time of our study, Dupont Pharma sold the Coumatrak business to Boehringer Mannheim. Due to this transaction, the Coumatrak system is no longer being manufactured, though they are still widely used across the United States.
[The authors can be reached at Creighton University School of Pharmacy and Allied Health, 2500 California Plaza, Omaha, NE 68178. (402) 280-2700.]
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