Influence of class I and II HLA alleles on inhibitor development in severe haemophilia A patients from the South of Brazil (original) (raw)
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The inhibitors – a challenge for the management of patients with hereditary haemophilia A
Romanian Journal of Internal Medicine
Introduction. Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management. Methods. Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included “haemophilia A”, “inhibitors”, “plasma-derived factor VIII” and “recombinant factor VIII”. Results. The risk factors for inhibitors occurrence may be patients-related (genetic and nongenetic) and treatment-related. The possibility of a correlation between the increased purity of factor VIII given as substitution treatment and the occurrence of inhibitors is discussed in the light of literature data. Plasma-derived factor VIII is less immunogenic, but not entirely safe from the point of view of the possibility of transmitting biological agents. It is obvious that there is not enough ...
Turkish Journal of Hematology, 2012
Objective: This study aimed to investigate the association between HlA class II alleles and the occurrence of FVIII inhibitor in Thai hemophilia A patients. Material and Methods: The distribution of HlA-DRb1 alleles and DQb1 alleles in 57 Thai hemophilia A patients and 36 blood donors as controls was determined using the PCR sequence-specific primer (PCR-SSP) method, and the association between the occurrence of factor VIII (FVIII) inhibitor and the presence of certain HlA class II alleles was investigated. Results: The frequency of HlA-DRb1*15 was higher in the hemophilia A patients with and without FVIII inhibitor, whereas that of DRb1*14, DRb1*07, and DQb1*02 was lower in the hemophilia A patients with FVIII inhibitor, as compared to controls. Interestingly, only the frequency of DRb1*15 was significantly higher in the patients with inhibitor than in the controls (P = 0.021). Moreover, the frequency of DRb1*15 in the patients with inhibitor was higher than in those without inhibitor (P = 0.198). Conclusion: The study's findings show that the DRb1*15 allele might have contributed to the occurrence of inhibitor in the Thai hemophilia A patients; however, additional research using larger samples and high-resolution DRb1 typing is warranted.
Haemophilia, 2014
A critical complication of factor VIII (FVIII) replacement therapy in Haemophilia A (HA) treatment is inhibitor development. Known genetic factors predisposing to inhibitor development include FVIII (F8) gene mutations, ethnicity, a family history of inhibitors and FVIII haplotype mismatch. The aim of this study was to characterize and correlate these genetic factors in a cohort of South African HA patients. This was a retrospective study that included 229 patients and involved the analysis of patient files, HA molecular and clinical databases and molecular analysis of the F8 gene haplotype. Of the 229 patients, 51% were of black ethnicity, 49% were white, 5% had mild HA, 4% were moderate and 91% were severe, 36% were int22 positive and 13% were inhibitor positive. Of the inhibitor positive patients, 72% were black patients. Inhibitors were reported in 27% of black int22 positive patients, 13% of black int22 negative patients, 9% of white int22 positive patients and 7% of white int22 negative. The H1 haplotype was more common in whites (75%) and H2 was more common in blacks (74%). H3 and H5 were only found in black patients and had a higher frequency of inhibitor development than H1 and H2. In this small HA cohort, black patients had a significantly higher frequency of inhibitor development and the results were indicative of an association between inhibitor development, ethnicity and haplotype.
2022
Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. Genetic factors have been shown to be a risk factor for the development of inhibitors. We aimed to identify the specific variations of the FVIII gene of patients with hemophilia A with inhibitors and their association with the inhibitor titer. Methods: Cross-sectional descriptive study. We included 12 Colombian patients from a health care provider, “Integral Solutions SD”, who underwent analysis of genetic material (DNA), which was reported by the Molecular Hemostasis Laboratory in Bonn, Germany. Results: All of these patients were diagnosed with severe hemophilia A with inhibitors; ages ranged between 6 and 48 years, with a median age of 13.5 years. Molecular analysis showed the inversion of intron 22 in six patients (50.0%), a small duplication in two patients (16.7%), the inversion of intron 1 in one patient (8.3%), a large deletion (8.3%), a nonsense mutation (8.3%) and a splicesite (8.3%), findings similar to those of other studies. A total of 58.3% of the patients presented inversion mutations with a high risk of developing inhibitors A total of 83.3% of the evaluated patients presented null mutations; however the presence of high inhibitor titers was 66.7%. The most frequent mutation was the inversion intron 22. Knowing the type of mutation and its association as a risk factor for generating inhibitors invites us to delve into other outcomes such as residual values of coagulation FVIII as well as its impact on the half-life of the exogenous factor applied in prophylaxis
Frequency of Factor VIII (FVIII) Inhibitor in Haemophilia A
Journal of the College of …, 2012
Haemophilia A (HA), inherited as an X-linked recessive trait, is the most common bleeding disorder caused by a deficiency or dysfunctional coagulation factor VIII (FVIII).1 Based upon the functional assay of factor VIII activity in the patient's plasma, haemophilia is classified as mild with > ...
INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY, 2019
Background: Neutralizing alloantibodies (inhibitors) is one of the complications that affect the morbidity and quality of life of hemophilia patient and can be caused by multifactorials. Genetic and inhibitors examination are not routine and expensive. Therefore, identification of non-genetic factors is important to predict the formation of inhibitors. Objective: To analyze non-genetic risk factors for the formation of factor VIII inhibitors in children with Hemophilia A. Methods: A cross-sectional study of hemophilia children aged 1-18 years at the pediatric hematology oncology outpatient clinic of Dr. Soetomo hospital in March-April 2018. Factors analyzed included the severity of hemophilia, early age of diagnosis, initial age of therapy, type of replacement therapy, frequency of factor VIII administration, and severity of bleeding by bleeding score. Statistical analysis using Chi square, Fisher, ANOVA and logistic regression analysis. Results: A total of 29 children were evaluate...
British Journal of Haematology
Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case-control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case-control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2-40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0Á96, 95% confidence interval (CI) 0Á36-2Á52) or for specific types of FVIII concentrates.