Registration Number
0212U004365,
0109U000463
, R & D reports
Title
Investigation of the risk factors for appearance of immune inhibitors in patients with hemophilia and other coagulation disorders
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Head
Loginsky Volodymyr Eustakhovych,
Registration Date
08-02-2012
Organization
State Institution Institute of Blood Pathology and Transfusion Medicine of National Academy of Medicfl Sciences of Ukraine
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Research object -629 patients (men) for hemophilia A, aged 1 to 75 years who were in hospital in the hematology department of the specialized children's hospital department, surgical care to patients with haemophilia at the five municipal hospital in Lviv or observed in the dispensary and methodological department of haemophilia and koahulopatiy SI "Institute of Blood Pathology and Transfusion Medicine of Ukraine NAMS" (Lviv). Aim: To clarify the role of genetic (internal) and envirolment (external) risk factors in the developement of inhibitors in hemophilia patients and their pathogenic significance in the development of resistance to substitution therapy. The studies performed revealed that the major risk factor for the inhibitor is the severity of hemophilia, sporadic character of disease, "inhibitory" family history, type of mutation in the genes of IL -10, TNF-alpha, CTLA-4. It was found that the presence of the inhibitor in patients with hemophilia causes significantly increased mortality in these patients. The analysis of family history of hemophilia patients found that sporadic hemophilia caused by new mutations and inhibitory 'family history affects the appearance of the inhibitor in these patients. Found that in patients with hemophilia G-frequency alleles significantly higher in patients with hemophilia A with a constant inhibitor compared with patients with transient inhibitor and does not differ from frequencies in hemophilia patients without inhibitors and the healthy. The frequency of genotypes of SNP - 1082 GA IL-10 which they form (AA, GG, AG) in patients with hemophilia does not depend on the availability of the inhibitors. Found that in patients with hemophilia A - frequency ratio and G-allele SNP -308 GA FTA-alpha is different in all groups of patients with hemophilia, as detected with inhibitor or without comparison with healthy, namely, the frequency of allele G significantly higher in these groups compared with healthy. The frequency of SNP -308 GA genotypes TNF-alpha, which they form (AA, GG, AG) significantly not different from control and not dependent on the presence of inhibitor. In patients with hemophilia A without inhibitor frequency of high expression genotype (GG-genotype) significantly higher compared with healthy.Revealed significantly higher frequency of -318 T gene CTLA-4, TT-genotype and phenotype of T compared with healthy individuals, which essentially does not depend on the appearance of inhibitor.The application of whole blood and FFP as the first drug significantly increases the risk of inhibitors, and the application of factor VIII concentrate significantly reduced ones. The highest incidence of inhibitor found in patients with hemophilia A with hemorrhagic manifestations which require a large dose of concentrates of factor VIII(IX), including major surgery.
Product Description
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Бужерак Н.Ф.
Дзісь Р.П.
Красівська В.В.
Оборін О.М.
Стасишин О.В.
Тушницький О.М.
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2020-04-02
