A recent study highlighted in Hematology Advisor explores the challenges of monitoring patients with hemophilia A after gene therapy, specifically focusing on the reliability of laboratory assays used to measure factor VIII (FVIII) activity. Hemophilia A is a genetic bleeding disorder caused by deficient or defective FVIII, and gene therapy offers a promising long-term treatment option by delivering functional FVIII genes to patients. However, as gene therapy becomes more common, accurately assessing bleeding risk and FVIII levels has become increasingly important.
Traditionally, two main types of laboratory assays are used to evaluate FVIII activity: the one-stage clotting assay and the chromogenic assay. The one-stage assay is widely used in clinical practice because of its simplicity and cost-effectiveness. The chromogenic assay, while less commonly employed, is considered more precise and less variable. These differences are generally minor in patients receiving standard FVIII replacement therapies. However, gene therapy introduces a new variable: the structure of the FVIII protein expressed following treatment can differ from traditional replacement products.
The article discusses a recent investigation into the reliability of the one-stage assay in patients who have received gene therapy for hemophilia A. The findings reveal that the one-stage assay tends to overestimate FVIII activity compared to the chromogenic assay in this specific population. This discrepancy is significant because it means that, while laboratory results may suggest adequate FVIII levels and a lower bleeding risk, patients may still be susceptible to spontaneous or breakthrough bleeding episodes.
Researchers analyzed post-gene therapy patient samples and found that the one-stage assay often reported higher FVIII activity than the chromogenic assay. This overestimation could potentially lead clinicians to underestimate a patient’s bleeding risk and adjust prophylactic treatment regimens inappropriately, putting patients at risk for dangerous bleeding events.
The study underscores the need for clinicians to be aware of these assay limitations when monitoring hemophilia A patients after gene therapy. The article suggests that, for these patients, the chromogenic assay may provide a more accurate assessment of FVIII activity and, by extension, bleeding risk. Additionally, the findings stress the importance of correlating laboratory results with clinical outcomes—namely, the patient’s actual bleeding history—rather than relying solely on assay data.
In conclusion, as gene therapies become increasingly integrated into hemophilia A treatment paradigms, the hematology community must adapt its monitoring strategies. Relying only on the one-stage assay could underestimate bleeding risk and compromise patient safety. Adopting the chromogenic assay or a combination of both tests, alongside careful clinical evaluation, will be crucial to ensure optimal care for patients receiving gene therapy for hemophilia A.
