Laboratory Methods of Heparin Monitoring, Part 3

Studies on APTT vs Anti-factor Xa assay
A retrospective, single-center, cohort study done by Vandiver & Vondracek (1995) reviewed medical records of 168 patients. The authors concluded that the protocol using anti-factor Xa assay to monitor UFH as compared to APTT were the following: (1) resulted in a higher percentage of test results within goal range (69% vs 41%, p=<0.001); (2) needed fewer monitoring tests (2.08 vs 2.73; p=0.001); and (3) required fewer dose adjustments per 24-hr period (0.62 vs 1.47; p<0.0001).

A prospective, randomized, unmasked, cohort study done by Rosborough (1999) demonstrated the feasibility of using Anti-factor Xa assay to monitor UFH. Two hundred sixty-eight patients with a variety of indications for UFH were studied.13 All patients received UFH based on ideal weight: 75 U/kg bolus and 20 U/kg initial infusion. Heparin assay was used to monitor 51% of the patients with a target therapeutic range of 0.3-0.7 U/ml. Conversely, the remaining 49% were monitored using APTT with a target range of 60-90 seconds. All samples were run using both methods, but only the result of the assigned assay was reported. Since there was gender imbalance between groups, a two-way ANOVA was used to statistically determine its significance. The analysis showed no statistical difference in any variable (p≥0.40).

Significant findings of this study were: (1) fewer monitoring tests/24 hours (p<0.001, two way ANOVA) and dosage changes(p<0.001, two way ANOVA) were observed in the anti-factor Xa group; (2) for both groups, 67% of the results were within therapeutic range for Anti-factor Xa assay; while the APTT was only within therapeutic range for 38% of the time in the APTT group and 33% in the Anti-factor Xa group; (3) monitoring UFH over 96 hours using anti-factor Xa assay costs $4.37 more than using APTT.

A recent retrospective, observational cohort study by Guervil et al (2011) compared the performance of APTT with anti-factor Xa in monitoring intravenous UFH infusion.12 The study reviewed patient medical records of 100 patients who received UFH between May 2005 and September 2009. The primary outcome of the study was the time to achieve therapeutic anticoagulation. The study showed significantly lesser mean time to achieve therapeutic range in the anti- factor Xa group as compared to the APTT group (p<0.0001). Those monitored using anti-factor Xa achieved therapeutic range in 28 hours; while, the APTT group required 48 hours. In addition, the authors observed that: (1) patients assigned to the anti-factor Xa group had more test values within the therapeutic range as compared to the APTT group; (2) fewer monitoring tests were performed using the anti-factor Xa assay (2.5 vs 2.8 with APTT); and (3) fewer infusion rate changes were needed when monitoring with the heparin assay (0.8 vs 1.6 with APTT).12

The findings of this study supports the advantages of anti-factor Xa assay as cited in the previous discussion. It also provides evidence that the need for fewer monitoring tests may compensate the relatively more expensive cost of the anti-factor Xa assay. And more important than cost efficiency, this study demonstrates that the need for fewer infusion rate adjustments might improve patient safety with respect to minimizing the probability of titration errors.

Why switch UFH monitoring assay from APTT to anti-factor Xa assay?
CAP and ACCP do not explicitly recommend anti-Factor Xa assay as the monitoring method of choice for UFH. Nevertheless, institutions are transitioning to this assay because it is a direct measure of heparin activity. Therefore, it is more specific to heparin as compared to APTT, since APTT primarily reflects the function of the intrinsic and common pathways of the coagulation cascade. It has also been noted in the previous discussion that anti-factor Xa assay is not affected by acute phase proteins like Factor VIII and Fibrinogen which is known to decrease the PTT response to heparin. Lastly, there are studies that demonstrated that anti-factor Xa assay is a cost-effective or at the minimum, cost neutral alternative to APTT, when labor costs are taken into consideration.

Conclusion
Anticoagulation therapy and laboratory monitoring methods are rapidly evolving. Drug monitoring should provide a very useful and clinically effective means of determining an optimal dose regimen for each individual. The ideal assay for monitoring unfractionated heparin remains a subject of debate. However, one cannot ignore the drawbacks of the current and widely used method, the APTT. The anti-factor Xa assay has been gaining momentum recently, and is continuing to do so because of its advantages over APTT. There are studies that have demonstrated that anti-factor Xa actually saves the hospital money; and more importantly, is a valuable tool for optimal patient care management.13,14,21 This is through less patient testing and monitoring needed; consequently, fewer dose adjustments are done. Therefore, the patient is stabilized quicker and released from the hospital earlier.

Bernadette V. Enderez, SBB(ASCP)CMMT(ASCP) is a clinical laboratory scientist at Hazel Hawkins Memorial Hospital and an MS student at Rush University in clinical lab management.

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