Discrepancies in Non-severe Hemophilia A. Experience in a Hemophilia Center in Argentina

SUELDO, E; MARCHIONE, V; BAQUES, A; PORSELLA, R; RADIC, P; ARIAS, M; ROSSETTI, LC; DE BRASI, C.D.

Congreso; Virtual Meeting of the International Society on Thrombosis and Haemostasis (ISTH); 2021

Background: Diagnosis of hemophilia A is generally based on the measurement of plasmafactor VIII activity using the one-stage assay (FVIII:OSA) or the two-stagechromogenic substrate assay (FVIII:CSA).The results of these methods showconsiderable discrepancy in about one-third of non-severe hemophilia Apatients. This can lead to failure in diagnosing HA or incorrectly classifyingthe severity of the disease.Aims: To evaluate the frequency of discrepancies betweenFVIII:OSA and FVIII:CSA, in the diagnostic classification of Patients withHemophilia.Methods: From 2012 to 2020, 107 patients with bleedingdisorders were diagnosed as Hemophilia A (HA). Hemostasis laboratory studieswere performed (Prothrombin time (PT), Activated Partial thromboplastin time(aPTT), Thrombin Time (TT), aPTT 1:1 mix, FVIII:OSA, FVIII:CSA, vW:Ag, vW:CoR).Patients were initially categorized into the different clinical categories byFVIII:OSA (Severe Hemophilia A: sHA <0.01IU/mL, Moderate Hemophilia A: mHA0.01-0.05 IU/mL, Mild Hemophilia A: miHA 0.05-0.40 IU/mL). FVIIIAssaydiscrepancy was defined as a two-fold or greater difference between the resultsof two assays. (FVIII:OSA/FVIII:CSA ≤ 0.5; FVIII:CSA/FVIII:OSA ≥ 2.0), correlating it with the clinical phenotype. Genotyping:PCR-amplification followed by conformation sensitive gel electrophoresis (CSGE)and Sanger sequencing.Results: 78Patients were diagnosed as sHA, 29 Patients as non-severe HA. 5 Patients withnon-severe HAshowed disagreement between the methods (Table 1).Conclusions:6% of patients with AH showeddiscrepancies, being 17% of patients with non-severe Hemophilia A. A lowerfrequency was found with respect to the bibliography. We conclude thatnon-severe haemophilia patients could benefit if chromogenic assay is includedin diagnosing and classification on severity haemophilia, and it also couldhelp to individualize group of patients that could benefit from earlyreplacement treatment.