Comparing One Stage, Chromogenic Assay Results and Discrepancies with Bleeding Phenotype and Genetic Variants in Females with Hemophilia A

Lakshmi Srivaths; Joanna Larson; Sepideh Saroukhani; Mohammed Said; Deborah Brown; Nidra Rodriguez; Neethu Menon; Miguel Escobar

doi:10.1016/j.jtha.2024.10.030

Comparing One Stage, Chromogenic Assay Results and Discrepancies with Bleeding Phenotype and Genetic Variants in Females with Hemophilia A

J Thromb Haemost. 2024 Nov 11:S1538-7836(24)00646-9. doi: 10.1016/j.jtha.2024.10.030. Online ahead of print.

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

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 VIII activity (FVIII:C) measurement is essential to assign correct diagnosis/severity. Assay discrepancies reported in Hemophilia A male patients, 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 IRB approval. Descriptive statistics, Chi-square, Fisher's exact and Bland-Altman plot analysis were applied.

Results: Abnormal ISTH BAT score was seen in 52% (FVIII:C<40 IU/dL: 72%/73%; FVIII:C>40 IU/dL: 41%/45%; by OSA/CSA respectively), more often in adults and post-menarchal 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 association of genetic variants with FVIII:C levels and bleeding phenotype were found.

Conclusions: Our study emphasizes the importance of evaluating female hemophilia A patients 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/severity assignment. Future larger, multi-center 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: Hemophilia A; assay; female; genetic variant; phenotype.

Published by Elsevier Inc.