From Carolyn McCarville: Hi George, My small laboratory is trying to figure out the best management of coag samples from patients receiving extended half life factor replacement products. We understand that many of the one stage clotting factor assays are inaccurate for the wealth of these products. One thing that we cannot get a straight answer for is whether or not we should be concerned with the accuracy of our silica-based PTT assay for these patients? It is understood that the PTT is inaccurate for patients receiving emicizumab. But what about Rebinyn, Aplrolix, Jivi, etc? Is this an area of concern for other small laboratories?
Hello, Carolyn, and thank you for your question. Yes, this is a concern, as the PTT is inaccurate in monitoring the various extended half-life [EHL] factor VIII and factor IX concentrates. The short answer is to switch to a chromogenic FVIII and chromogenic FIX assay, both of which have been recently developed and offered by several in vitro diagnostics manufacturers. This may not be simple for smaller labs as the reagents may be “single source” and instrument-dependent.
The variability of the PTT-based factor assay is a result of the variety of particulate activators in the PTT reagents like silica, Celite, ellagic acid, or kaolin, and their various responses to the EHL formulations using pegylation, Fc fragment fusion, albumin fusion, or other chaperone proteins. If PTT is your only choice, assuming you can identify the EHL concentrate used in your hemophilia center, your PTT should be calibrated to the specific concentrate using commercial calibrators or spiked samples. You should also communicate with your center to describe the limitations of the assay.
For Hemophilia A, many centers are using emicizumab [HemLibra®], which cannot be measured using a clot-based assay. The key need in emicizumab therapy is to be able to assay FVIII in cases of breakthrough bleeding. In this instance, the chromogenic VIII is your only choice.
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