Abstract Number: PB0636
Meeting: ISTH 2021 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Diagnosis of hemophilia A is generally based on the measurement of plasma factor VIII activity using the one-stage assay (FVIII:OSA) or the two-stage chromogenic substrate assay (FVIII:CSA). The results of these methods show considerable discrepancy in about one-third of non-severe hemophilia A patients. This can lead to failure in diagnosing HA or incorrectly classifying the severity of the disease.
Aims: To evaluate the frequency of discrepancies between FVIII:OSA and FVIII:CSA, in the diagnostic classification of Patients with Hemophilia.
Methods: From 2012 to 2020, 107 patients with bleeding disorders were diagnosed as Hemophilia A (HA). Hemostasis laboratory studies were 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 by FVIII:OSA (Severe Hemophilia A: sHA <0.01 IU/mL, Moderate Hemophilia A: mHA 0.01-0.05 IU/mL, Mild Hemophilia A: miHA 0.05-0.40 IU/mL). FVIII Assay discrepancy was defined as a two-fold or greater difference between the results of 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: 78 Patients were diagnosed as sHA, 29 Patients as non-severe HA. 5 Patients with non-severe HA showed disagreement between the methods (Table 1).
Patients | F8-genotype variants | FVIII:OSA | FVIII:CSA | OSA/CSA |
1 | c.6246C>A p.(Ser2082Arg) | 2-5 | 1-2.5 | 2.0 |
2 | c.5399G>A p.(Arg1800His) c.3780C>G (rs1800291) p.(Asp1260Glu) | 2-2.9 | 0.8-1 | 2.5-2.9 |
3 | c.5508G>T p.(Trp1836Cys) c.3780C>G (rs1800292) p.(Ser1288=) |
8-10 | 2-4 | 2.5-4.0 |
4 | c.5981T>C p.(Leu1994Pro) c.5998+91T>A rs4898352 c.3864A>C rs1800292 p.(Ser1288=) |
2-5 | 0.9-1 | 2.2-5.0 |
5 | c.5981T>C p.(Leu1994Pro) c.5998+91T>A rs4898352 c.3864A>C rs1800292 p.(Ser1288=) |
2.2-5 | 0.8-1 | 2.8-5.0 |
Conclusions: 6% of patients with AH showed discrepancies, being 17% of patients with non-severe Hemophilia A. A lower frequency was found with respect to the bibliography. We conclude that non-severe haemophilia patients could benefit if chromogenic assay is included in diagnosing and classification on severity haemophilia, and it also could help to individualize group of patients that could benefit from early replacement treatment.
To cite this abstract in AMA style:
Sueldo E, Porsella R, Rossetti LCR, Marchione V, Radic P, De Brasi C, Baques A, Arias M. Discrepancies in Non-severe Hemophilia A. Experience in a Hemophilia Center in Argentina [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/discrepancies-in-non-severe-hemophilia-a-experience-in-a-hemophilia-center-in-argentina/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/discrepancies-in-non-severe-hemophilia-a-experience-in-a-hemophilia-center-in-argentina/