COAGULATION STUDIES APTT interference Pre-analytical Analytical/clinical


Tube type (EDTA) Sample volume (↓)


Lupus anticoagulant ↑ FVIII ↑ Fibrinogen


Medication-induced


Coumadin Thrombolytics DTIs


Pegylated drugs n APTT prolongation n Shortened APTT Activated partial thromboplastin time and the need for exclusion criteria.


within that range for longer. One study also highlighted the lack of concordance between APTT and anti-Xa results, with this demonstrated in more than 50% of the samples measured.


Limitations of APTT Anti-Xa is a highly specific assay, providing a more direct and therefore more accurate measurement of heparin activity. It can be used more widely, for low molecular weight heparin (LMWH) as well as UFH (with either hybrid or dedicated calibrations), fondaparinux, and for the direct oral anticoagulants (DOACs) that inhibit factor Xa directly. Stago’s anti-Xa assay is free from the additive dextran sulphate and exogeneous antithrombins, and not subject to FVIII/Fib interferences. While APTT heparin monitoring is often the preserve of the specialist laboratory, it is the specific case of UFH that makes it tricky due to the importance of the pre-analytical stage. Stago’s fully automated STA Liquid Anti-Xa test is more workflow efficient, delivering a very rapid turnaround time (TAT) of less than six minutes. It can be run in the core laboratory across all Stago analysers; and no longer requires specialist facilities and staff. The Stago assay is calibrated to international standards and remains stable at 2–8°C for seven days – significantly longer than other manufacturers. The standard target range for


heparin is usually 0.3–0.7 U/mL. When administering intravenous UFH, therapeutic levels must be achieved rapidly and then monitored to ensure this is maintained at consistent levels. Monitoring with anti-Xa achieves target anticoagulation more quickly and maintains this for longer, with fewer dosage adjustments. There is also less need for repeat testing.


Workflow-efficient assay When monitoring with APTT, this must first be done every four to six hours, to establish therapeutic levels, and then at least every 24 hours. The patient’s target APTT ratio is 1.5–2.5 times the control value. When the ex vivo Brill Edwards curve was introduced in 1993, the limitations of APTT were already evident. To provide a valid curve, it was best practice to require at least 50 heparin samples to set the control value. An attempt was made in 2013 by Marlar and Gausman6


to ease the


burden on laboratories with their study indicating that an accurate heparin therapeutic range could be achieved by reducing the specimen demand to the 20 or 30 required in current practice. The chromogenic assay immediately solves the dilemma for laboratories that may have difficulty validating their APTT therapeutic range due to sample availability.


An APTT assay needs to be validated for each new reagent lot in line with


Anti-Xa is proving to be a clinically important guide to therapy, especially for the critically ill and for those undergoing complex surgical procedures


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Hybrid curve evaluation However, they first had to be sure they could successfully make the change from a double to a single spin of samples in the centrifuge. Talking about the transition, Mr Buddhadev added: “We operate in a very busy environment and, to be confident that we could incorporate the heparin assay into our routine workflow, it was essential to evaluate the assay on a hybrid curve calibration in our special haematology laboratory. “The advantage of the hybrid calibration curve is that both UFH and LMWH can be monitored using the same assay. Pre-analytical preparation becomes much easier when staff no longer have to worry about requesting a specific test.


“It enabled us to see the impact APRIL 2022 WWW.PATHOLOGYINPRACTICE.COM


UK guidelines and for this laboratories already need to have access to anti-Xa. Owing to differing sensitivities between APTT reagents and between lots of the same reagent, APTT must be calibrated to 0.3–0.7 anti-Xa.


Anti-Xa in the routine laboratory


The blood sciences unit at the University of Leicester Hospitals NHS Trust has been an advocate of anti-Xa testing since the haemostasis team took the decision to transform how it carried out heparin monitoring. Up to then, it was relying on APTT with only limited use of anti-Xa.


The trust has been a Stago customer since 2008 and operates eight Stago STA R Max 2 systems across its three sites (Leicester Royal Infirmary, Leicester General and Glenfield Hospital). Until December 2020, however, it only ran the STA Liquid Anti-Xa assay in the infirmary’s specialist haematology laboratory, on just one analyser and mainly during core hours. Bhakta Buddhadev, the senior biomedical scientist for haemostasis, explained: “This all changed when demand for 24/7 heparin monitoring increased during the peak of the COVID crisis. At that point, we took the decision to switch to running the assay routinely, round-the-clock on all Stago systems and at all three hospital sites. “Once we made the change, the clinical impact was seen almost immediately, with rapid TAT of results benefitting patient treatment management. At a time when staff were working under increased pressure, they saved valuable time by not having to double spin in the centrifuge and store aliquots ready for transfer to our specialist laboratory.”


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