Using the Anti-Xa Heparin Assay to Monitor Heparin


Vol. 20 • Issue 9 • Page 68

Case Study

In the winter of 2009, I took a close look at how hospitals in my system were monitoring patients on unfractionated heparin.

At the time, activated partial thromboplastin time (heparin aPTT) was used to determine and adjust intravenous unfractionated heparin levels (UFH). Although the aPTT test was well-known and relatively inexpensive to perform, it is an indirect measurement and never designed to directly measure heparin concentration. For some patients, using the aPTT test to monitor heparin can result in several dosage changes requiring frequent blood draws to achieve therapeutic heparin levels. Depending on the coagulation platform, methodology and aPTT reagent being used, the therapeutic heparin range can vary from hospital to hospital.

Brill-Edwards Curve

Each year when the hospital received a new lot of coagulation reagents, they needed to verify their heparin therapeutic range accuracy through a Brill-Edwards curve. Briefly, the curve is created by collecting plasma samples from patients receiving only heparin (no coumadin or other anticoagulant therapies) and frozen. Anti-Xa and aPTT tests were then run on the samples. The Anti-Xa test was plotted on the X-axis and the aPTT test was plotted on the Y-axis. A linear regression line representing the Anti-Xa and aPTT relationship was then determined. Therapeutic Anti-Xa heparin levels of 0.30-0.70 IU/mL are used to determine the therapeutic heparin aPTT range from this regression line.

The major challenge in creating a Brill-Edwards curve was finding enough citrate specimens from patients only on unfractionated heparin. Most hospital patients, when presenting with blood clot symptoms, were placed on coumadin and heparin simultaneously. Even as a group of five hospital laboratories, the labs could only obtain 40 specimens to create the curve.

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Full Automation

The Anti-Xa test was fully automated using Diagnostica Stago‘s STA Compact® benchtop hemostasis analyzer, and the overall cost seemed affordable. Additionally, the Anti-Xa test took about the same time to run as an aPTT assay.

A team gathered more data on the Anti-Xa test and its potential for monitoring heparin therapy. We found that the Anti-Xa assay was not only a better, more direct heparin concentration measurement, but it was financially feasible for the hospital system to transition to Anti-Xa testing, a higher cost per test, depending on each lab’s test volume. If one were to look at a simple per-test kit cost comparison between aPTT and Anti-Xa, the aPTT would logically win. We needed to find ways to make this financially possible for the lower volume labs; Diagnostica Stago provided different Rotachrom Anti-Xa reagent sizes, helpful for the smaller labs. The next step was to convince laboratory and hospital administration officials to convert to Anti-Xa testing.

Making the Case

First, we presented information and clinical data on Anti-Xa testing to the system’s Pharmacy and Therapeutics (P&T) committee. We maintained that the Anti-Xa test was a safer, direct measurement of heparin in patients and showed that the test was fully automated, comparable to the aPTT turnaround time and offering good reimbursement versus cost per test. P&T granted approval to proceed with the Anti-Xa conversion.

Technical staff, including pharmacists, laboratory technicians, nurses and physicians, at all five hospital laboratories were introduced to and trained on the Anti-Xa test with assistance from Stago personnel. This was a major undertaking that had to be done as close to the transition date as possible. During training, our team presented a compelling message using a sample Brill-Edwards method (Figure) showing the intersection of both therapeutic ranges and revealing where aPTT results could incorrectly categorize a patient as subtherapeutic or supratherapeutic. As heparin is one of the most dangerous drugs administered in a hospital setting, you could hear a pin drop when we presented this chart, as people realized the impact this had on patient care.

New Test Codes

Two new Anti-Xa test codes were created in the hospital and laboratory computer systems (HIS and LIS, respectively)-one to monitor UFH and one for low molecular weight heparin (LMWH), as Stago’s Anti-Xa assay is appropriate for both. Stago provides calibrators for a “hybrid” calibration curve for Anti-Xa testing. Each test code would have unique therapeutic ranges and critical limitations. A baseline aPTT test screened for other coagulopathies (factor deficiencies, inhibitors, etc.). Once on UFH or LMWH, the patient could be monitored with the Anti-Xa test. The hospital’s HIS used logic to examine the patient’s medication history for a UFH protocol or LMWH drug and assist physicians and nurses in choosing the right test. Stago’s educational materials were also available on the computer systems. Pharmacy updated all the dosing nomograms and protocols on the paper order forms and in the computer systems.

Cate Cronin is Hematology and Coagulation technical specialist for UC Health (formerly The Health Alliance) in Cincinnati.

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