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DOI: 10.1055/s-0044-1786029
The Role of Clot Waveform Analysis and Related Parameters in the Diagnosis and Treatment of Hemophilia A
Funding This study was supported by National Natural Science Foundation of China (82073367 to M.X.), Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (2022-LCYJ-PY-20 to M.X.), and National Key Research and Development Program of China (2023YFC2415000 to M.X.).
Abstract
Background Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency or defect in factor VIII (FVIII).
Methods We investigated the role of clot waveform analysis (CWA) of activated partial thromboplastin time in the diagnosis and therapeutic monitoring of HA. The changes in CWA parameters the maximum clotting velocity (|Min1|), maximum clotting acceleration (|Min2|), and maximum clotting deceleration (|Max2|) were detected among mild, moderate, and severe HA groups.
Results As the severity of HA subtypes increased, the levels of |Min1|, |Min2|, and |Max2| progressively decreased (p < 0.05). Receiver operating characteristic curve analysis showed that |Max2| and |Min2| were more effective than |Min1| in distinguishing different types of HA patients, with higher diagnostic efficacy. The standard curves based on Actin FSL reagent for normal and low levels of FVIII:C-|Max2| were established, with R2 values of 0.98 and 0.99, respectively. These curves can be utilized for monitoring during replacement therapies involving full-length recombinant FVIII and B-domain-deleted FVIII. Thirty cases of HA patients utilized the FVIII-|Max2| standard curve to obtain individual pharmacokinetics characteristic parameters. The clearance, half-life (t1/2), time to FVIII:C of 1% above baseline (tt1%), and predicted dosage showed no statistically significant differences compared with one-stage assay (p > 0.05).
Conclusion CWA is an economical and practical tool, and its related parameters are associated with the severity of HA. It has promising clinical prospects in predicting FVIII:C levels and individualized treatment when HA patients undergo replacement therapy.
Keywords
clot waveform analysis - factor VIII - hemophilia A - pharmacokinetics - individualized treatmentEthical Approval Statement
Ethical approval was obtained from Nanjing Drum Tower Hospital Medical Ethics Committee (approval number 2022-360-03). Written informed consent was obtained from all the patients. All procedures were conducted in accordance with the ethical principles of the Declaration of Helsinki.
Authors' Contribution
M.X., G.S., Y.W. designed the experiments, analyzed data, and wrote the paper. G.S. and Y.W. performed the experiments. L.Z. helped with the experiments.
* These authors contributed equally to this work.
Publication History
Received: 06 September 2023
Accepted: 15 March 2024
Article published online:
16 April 2024
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