Blood tests may vary in measuring factor VIII after treatment
Study found greater discrepancies at lower levels and later after infusion
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- Different blood tests can give different factor VIII activity readings after Altuvoct treatment, complicating monitoring.
- Discrepancies were greater when factor VIII activity was lower and more time had passed since an infusion.
- Careful interpretation of test results and better standardized monitoring may help guide treatment decisions.
Blood tests can give different readings of factor VIII (FVIII) activity after treatment with Altuvoct (efanesoctocog alfa), marketed as Altuviiio in the U.S., a study found. The differences were greater when FVIII levels were low or several days had passed since an infusion, highlighting the need for careful interpretation; FVIII is a clotting protein that is deficient in hemophilia A.
“No test showed consistent agreement with the reference assay, warranting caution and better standards,” researchers at Strasbourg University Hospital in France wrote in “Assay or Astray? Discrepancies in Efanesoctocog alfa Monitoring,” published in Research and Practice in Thrombosis and Haemostasis.
Why factor VIII testing matters with Altuvoct
Hemophilia A is caused by a deficiency of FVIII, a protein that helps blood clot, which can lead to excessive bleeding. Given as an infusion into the bloodstream, Altuvoct is a factor replacement treatment that supplies working FVIII to help prevent or control bleeding. Its active ingredient, efanesoctocog alfa, was designed to remain active in the body longer than natural FVIII.
Because FVIII activity may need to be monitored in people receiving Altuvoct, the researchers studied how closely commonly used tests agreed when measuring that activity in blood. These results can help doctors make treatment decisions.
The study compared six commonly used FVIII assays with a reference assay called the Actin FSL one-stage assay (AFSL OSA). A one-stage assay measures FVIII activity based on how quickly a clot forms in a laboratory reaction.
The researchers tested Altuvoct in two ways. First, they added known amounts of Altuvoct to FVIII-deficient plasma, the clear liquid part of blood. These are called spiked samples. Second, they tested 73 blood samples from 19 patients with severe hemophilia A who were receiving Altuvoct. Comparing the two allowed the researchers to see how test performance in lab-made samples differed from that in patient samples.
The researchers defined acceptable agreement as a result between 80% and 120% of the reference assay. In the spiked samples, chromogenic tests calibrated with human plasma overestimated FVIII activity by about 37% to 94%. A chromogenic assay measures the clotting protein’s activity through a chemical reaction that produces a color, with a stronger color signal indicating greater activity.
Lab-made and patient samples produced different results
A chromogenic test using a calibrator specific for Altuvoct — a laboratory standard designed to account for the treatment’s particular characteristics — performed much better in the spiked samples, with results only 2% to 16% higher than the reference. Results from the one-stage assays varied by test: some were close to the reference, while others underestimated FVIII activity, with the degree of underestimation varying by assay and FVIII level.
The results changed substantially with blood samples from patients. None of the six comparison assays consistently stayed within the acceptable range across all FVIII levels. Some reported higher FVIII activity than the reference, whereas the chromogenic test calibrated specifically for Altuvoct tended to report lower FVIII activity, especially at lower FVIII concentrations.
The differences also depended on how much time had passed since patients last received Altuvoct. Around one to three hours after an infusion, some blood tests performed reasonably well, but differences became larger at later time points and when FVIII activity was lower. For example, some one-stage assays tended to overestimate FVIII activity at later time points.
Overall, results from patient samples differed from those in the lab-made samples. The researchers said the differences may reflect how Altuvoct behaves in the body over time, although the study did not investigate the cause of the discrepancies. The findings suggest that results from spiked samples alone may not fully predict how the tests perform in patient samples.
“The observed discrepancies may have clinically relevant consequences for treatment decisions,” the researchers wrote. They said FVIII activity results should therefore be interpreted cautiously. “Further studies are required to optimize and standardize [Altuvoct] monitoring in clinical practice,” the researchers concluded.
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