Practical Two-Point Pharmacokinetic Protocol in Hemophilia A

The importance of the individual pharmacokinetic profile

Prophylactic administration of missing factor concentrates in individuals with hemophilia A and B reduces joint bleeding and improves their quality of life. There is evidence that raising factor VIII (FVIII) levels above 1 IU/dl reduces the risk of bleeding. Current guidelines for prophylaxis in individuals with severe hemophilia advocate aiming for FVIII > 1 IU/dl.

The achieved FVIII levels are primarily influenced by the individual pharmacokinetic (PK) profile. To optimize prophylaxis outcomes, it is suitable to focus on its individualization precisely concerning the PK profile. Traditional PK testing in individuals with hemophilia A, however, requires a washout period of at least 72 hours and 5-11 blood samples taken at pre-specified time points after factor infusion. This process is, of course, burdensome for both patients and treatment centers.

Simplified and less burdensome approach to pharmacokinetics

Methodology and study course

The cited study, which also took place in Czech hemophilia centers, focused on comparing two protocols for PK profile testing – the “traditional” one, using 6 samples and an at least 72-hour washout period, and the “practical” one, where 2 samples are taken during a single visit to the center without a washout period. In this case, the first sample was taken upon arrival at the center, 24 hours after the previous infusion, and the second sample 3 hours after the infusion administered at the center right after the first sample collection. This method used a Bayesian model for PK assessment.

The study involved 39 men with severe hemophilia A (defined as FVIII level < 2%) without the presence of FVIII inhibitors. The study was prospective, and participants underwent both the traditional and practical PK profile evaluations. FVIII levels were analyzed using both a one-stage clotting assay and chromogenically. Blood group and von Willebrand factor antigen levels were also determined. PK parameters were analyzed using the Advate myPKFiT tool.

Results

There was observed moderate to almost perfect agreement between PK parameters obtained from the 2- and 6-point PK protocols for values measured with the one-stage clotting assay and nearly perfect agreement for values measured chromogenically.

Clinical implication of study findings

According to this study, a pharmacokinetic protocol with only 2 samples, without a washout period, can be used in routine practice during a short visit to a hemophilia center. This protocol provides sufficient accuracy compared to the traditional, time-consuming method of PK assessment, making it a suitable approach for optimizing hemophilia prophylaxis.

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Source: Blanchette V. S., Zunino L., Grassmann V. et al. A practical, one clinic visit protocol for pharmacokinetic profile generation with the ADVATE myPKFiT dosing tool in severe hemophilia A subjects. Thromb Haemost 2021 Oct; 121 (10): 1326−1336, doi: 10.1055/a-1376-0970.