INVESTIGADORES
ABELLEYRO Miguel Martin
congresos y reuniones científicas
Título:
INHIBITOR RISKS ESTIMATION ASSOCIATED WITH F9 GENOTYPE TYPES IN PATIENTS WITH SEVERE HAEMOPHILIA B: ARGENTINE VS EAHAD DATABASE
Autor/es:
RADIC CP; ZIEGLER B; MARCHIONE VD; WAISMAN K; ABELLEYRO MM; WILLIAMS M; NEME D; DE BRASI CD; ROSSETTI LC
Lugar:
Milan
Reunión:
Congreso; Virtual Meeting of the International Society on Thrombosis and Haemostasis ISTH; 2020
Institución organizadora:
International Society on Thrombosis and Haemostasis
Resumen:
Background: Haemophilia B (HB), an X-linked coagulopathy affecting 1:30,000 males worldwide, issuccessfully treated by substitution of the decient FIX. Development of inhibitory antibodies againsttherapeutic FIX represents a major clinical complication impacting patient?s quality of life and the economyof National health systems. FIX-inhibitors typically associate with severe allergic and/or anaphylacticreactions.Aims: We aimed to estimate the FIX inhibitor-risks associated with F9-genotypes in previously untreatedpatients (PUP) with severe-HB from Argentina (about 1/3 of all HB-cases countrywide) and from theInternational F9-variant database EAHAD (European Association for Haemophilia and Allied Disorders,http://f9-db.eahad.org/).Methods: HB-causative variants were characterised by application of a cost-effective F9-analysis algorithmincluding 12 PCR-amplications, primary detecting large-F9-deletions in hemizygous probands, small-variant screening by high-resolution CSGE and Sanger sequencing. Variant pathogenicity was evaluatedfollowing ACMG criteria (American College of Medical Genetics).Results: Our Argentine case/control study, inhibitor[+]/inhibitor[-], included separated random samples of13 cases and 67 controls. To correct the relative enrichment in inhibitor[+] cases(all inhibitor[+] cases with severe-HB were included) -as literature estimates 3-12% of FIX-inhibitordevelopment in severe-HB, F9-genotype inhibitor-risks were estimated by ORs (CI95%)(Fisher exact P-values) that normalise those case/control unbalance. Severe-HB patient series from EAHAD, in whichinhibitor status was reported, present a similar enrichment in inhibitor[+] cases.Argentine series of F9-missense variants showed the lowest FIX-inhibitor-risks, equal to EAHAD, whilenonsense showed moderately augmented inhibitor-risks, similar to EAHAD. Argentina vs EAHADgureswere consistent indicating the highest inhibitor-risks classifying all types of F9-deletions together, which iseven more important in cases with deletions of the entire-F9, and just doubling the inhibitor-risks but non-signicantly in partial F9-deletions. Table.Conclusions: Ourndings reveal similar estimations of F9-genotype associated inhibitor-risks in severe-HBPUPs series from Argentina and EAHAD. Data of F9-variant-specic inhibitor-risks may providehaematologists with key evidence for designing therapeutics and follow-up regimes.