The influence of dead space in blood sampling needle on FVIII level and pharmacokinetic profiles in children with hemophilia

ABSTRACT

Objective

To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia.

Methods

Children (<18 years) with severe hemophilia A were enrolled. After three days’ washout-period, blood samples were collected at pre-dose, 1 h, 3 h, 9 h, 24 h and 48 h post-infusion. At each timepoint, two 2 mL vacuum tubes with 3.2% trisodium citrate were used. The first tube was signed as ‘non-standard’ (NS) and the second tube was signed as ‘standard’ (S). FVIII activities were evaluated by one-stage assay. WAPPS-Hemo was used to generate PK profiles like half-life time (t_1/2), clearance (CL), trough level and time to 1, 2 and 5IU/dL after a dose of 50 ± 10IU/dL. The FVIII activities at 9 h and 24 h post-infusion were put into WAPPS and thus brought four combinations by true or biased FVIII level that used.

Result

Compared with standard-collected blood samples, prolonged APTT results (P-values < 0.01) and decreased FVIII activity (P-values < 0.05) were revealed in those non-standard blood samples. The corresponding bias was in positive relation to both APTT-S (r = 0.44, P < 0.0001) and FVIII-S level(r = 0.68, P < 0.001). The FVIII bias percentage got larger as FVIII-S level reduced (r = −0.24, P < 0.01). During the four combinations of FVIII activity at 9 h and 24 h, statistically longer t_1/2, lower CL and longer time to 1, 2 or 5IU/dL were observed in 9H-S&24H-S group and 9H-NS&24H-S group.

Conclusion

While using vacuum tubes for clotting indicators and PK profiles, the dead space of blood sampling needle should be eliminated in advance.

KEYWORDS:

• APTT
• dead space
• factor VIII
• hemophilia
• pharmacokinetics
• children
• half-life time
• blood sampling

Acknowledgements

We thank Dr. Alfonso Iorio and his team for their generous help of WAPPS-Hemo.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics statements

The studies involving human participants were reviewed and approved by the Ethics Committee of Beijing Children’s Hospital, Capital Medical University, National Children’s Medical Center. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

Authorship

Ai Di and Kun Huang performed the PK tests, analyzed the data, and wrote the manuscript. Yingzi Zhen and Gang Li helped with collection of blood samples, did the laboratory tests and wrote part of the manuscript. Zhenping Chen reviewed and modified the manuscript. Runhui Wu designed the study and reviewed the manuscript.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported in part by grants from Bayer the LEAP Investigator Initiated Research (20006429).