Blood Res.  2024;59:19. 10.1007/s44313-024-00018-6.

Assessment of the phenotypic severity of hemophilia A: using rotational thromboelastometry (ROTEM) and APTT‑clot waveform analysis

• Gupta D
• Arya V
• Dass J
• Gupta N
• Kalra M
• Sachdeva A
• Kotwal J

• KMID: 2562523
• DOI: http://doi.org/10.1007/s44313-024-00018-6

Abstract

Background
Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10–15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA).
Methods
Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded.
Results
A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/ moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters.
Conclusion
ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.

Keyword

Hemophilia A; ROTEM; APTT-CWA; Phenotype severity; Bleeding disorder; Bethesda assay

Figure

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  Fig. 1 Temograms of the study population in Group I, Group II, Group III, and Group IV

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  Fig. 2 ROC curve analysis to calculate CT, CFT (A), MCF, and alpha angle (B) value for predicting mild/moderate hemophilia A with severe phenotype when compared to severe hemophilia A with inhibitors with severe phenotype (Group II vs. Group III)

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