Comparative Study

. 2025 Feb;23(2):504-512.

doi: 10.1016/j.jtha.2024.10.030. Epub 2024 Nov 12.

Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A

Lakshmi Srivaths¹, Joanna Larson², Sepideh Saroukhani³, Mohammed Said⁴, Deborah Brown⁵, Nidra Rodriguez⁶, Neethu Menon⁵, Miguel Escobar⁷

Affiliations

¹ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. Electronic address: Lakshmi.V.Srivaths@uth.tmc.edu.
² Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
³ Division of Clinical and Translational Sciences, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center, Houston, Texas, USA.
⁴ Department of Pediatrics, Alexandria University, Alexandria, Egypt.
⁵ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
⁶ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
⁷ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.

PMID: 39536816
DOI: 10.1016/j.jtha.2024.10.030

Comparative Study

Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A

Lakshmi Srivaths et al. J Thromb Haemost. 2025 Feb.

. 2025 Feb;23(2):504-512.

doi: 10.1016/j.jtha.2024.10.030. Epub 2024 Nov 12.

Authors

Lakshmi Srivaths¹, Joanna Larson², Sepideh Saroukhani³, Mohammed Said⁴, Deborah Brown⁵, Nidra Rodriguez⁶, Neethu Menon⁵, Miguel Escobar⁷

Affiliations

¹ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA. Electronic address: Lakshmi.V.Srivaths@uth.tmc.edu.
² Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
³ Division of Clinical and Translational Sciences, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Biostatistics/Epidemiology/Research Design (BERD) Component, Center for Clinical and Translational Sciences (CCTS), The University of Texas Health Science Center, Houston, Texas, USA.
⁴ Department of Pediatrics, Alexandria University, Alexandria, Egypt.
⁵ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.
⁶ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA.
⁷ Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA; MD Anderson Cancer Center, The University of Texas, Houston, Texas, USA; Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center, Houston, Texas, USA.

PMID: 39536816
DOI: 10.1016/j.jtha.2024.10.030

Abstract

Background: Increasing evidence in females with hemophilia A has shown significant bleeding symptoms. Accurate factor (F) VIII activity (FVIII:C) measurement is essential to assign correct diagnosis and severity. Assay discrepancies reported in male patients with hemophilia A are not well studied in females.

Objectives: Our research sought to assess the association of FVIII:C levels by one-stage versus chromogenic assays and the assay discrepancy with bleeding phenotype and genetic mutation in females with hemophilia A.

Methods: Data from 64 females with hemophilia A from our center were reviewed with center's institutional review board approval. Descriptive statistics, chi-squared, Fisher's exact, and Bland-Altman plot analysis were applied.

Results: Abnormal International Society on Thrombosis and Haemostasis bleeding assessment tool score was seen in 52% (FVIII:C <40 IU/dL: 72%/73%; FVIII:C ≥40 IU/dL: 41%/45%; by one-stage and chromogenic assays, respectively), more often in adults and postmenarchal patients. Assay discrepancies were present, direct more often than inverse. Based on one assay result only, 11 (17%) patients would have been incorrectly diagnosed and 1 (1.5%) patient would have been assigned incorrect hemophilia severity. No associations of genetic variants with FVIII:C levels and bleeding phenotype were found.

Conclusion: Our study emphasizes the importance of evaluating female patients with hemophilia A for bleeding phenotype. Our study is the first to document prevalence of assay discrepancies exclusively in females with hemophilia A, which can lead to inaccurate diagnosis and severity assignment. Future larger, multicenter studies are needed to validate our findings, to help develop recommendations regarding the appropriate use of assays for accurate diagnosis and to further elucidate the association of genetic variants with bleeding phenotype and assay discrepancies.

Keywords: assay; female; genetic variant; hemophilia A; phenotype.

Published by Elsevier Inc.

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Conflict of interest statement

Declaration of Competing Interests N. R.: Medical board advisor for Sanofi, Genentech. M. Escobar: Received Honorarium for participating in advisory board and/or consultation - Bayer, Sanofi, Hemabiologics, Pfizer, Regeneron, LFB, Roche, Genentech, Takeda, NovoNordisk, CSL Behring, NBDF, Magellan, Biocryst; The University of Texas receives financial support for participating in research studies sponsored by - Bayer, Sanofi, Regeneron, Biomarin, LFB, Takeda, ATHN, UniQure. All other authors have no conflict of interest to disclose.

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Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A

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Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A

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