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Thromb Haemost
DOI: 10.1055/s-0044-1786029
New Technologies, Diagnostic Tools and Drugs

The Role of Clot Waveform Analysis and Related Parameters in the Diagnosis and Treatment of Hemophilia A

Guanghao Song‡   *
1   Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
,
Yangbin Wang‡   *
1   Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
,
Lilei Zhang
1   Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
,
Mao Xia
1   Department of Laboratory Medicine, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
› Author Affiliations 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.).
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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 treatment

Ethical 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.


Supplementary Material



Publication History

Received: 06 September 2023

Accepted: 15 March 2024

Article published online:
16 April 2024

© 2024. Thieme. All rights reserved.

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