Contributions
Abstract: PB1806
Type: Publication Only
Background
The intensity and frequency of hemorrhagic manifestations in patients with certain form of hemophilia may vary. There are still no convincing data explaining the different clinical course of hemophilia. Despite comprehensive substitutive hemostatic therapy, some patients develop severe arthropathy requiring surgical support. Frequency of purulent complications after arthroplasty in patients with hemophilia is higher than in the general population.
Aims
To study possible genetic factors that aggravate the course of hemophilia and increase the risk of complications after orthopedic operations.
Methods
96 patients with severe hemophilia and arthropathy who underwent endoprosthesis replacement of the affected joint were included in the study. The mean age was 39.6 years (min 23, max 68): 75 (78.1%) with hemophilia A, 16 (16.7%) with hemophilia B and 5 (5.2%) with an inhibitory form of hemophilia . Histological studies of bone tissue in the area of the affected joint, taken during arthroplasty of the joint, were performed. Patients were examined for antibodies to hepatitis C and hepatitis C RNA. DNA samples were examined for genetic markers of hereditary hemochromatosis (mutations H63D and C282Y of HFE gene), thrombophilia (F5, MT677, MT1298, F2), polymorphisms of the vitamin D receptor gene (Taq1, Apa1 and Fok1) by means of real-time allele-specific polymerase chain reaction.
Results
Homozygous Taql and Apal polymorphisms of the vitamin D receptor gene in hemophilia patients was found in 7.3% and 18.8%, respectively, which corresponds to the literature data for the Russian population. Homozygous Fokl marker was detected in 27 patients (28%), which is 2.8 times more frequent than in general population (10%). Nine heterozygous cases (9.4%) of C282Y HFE gene mutations (none homozygous) and 38 heterozygous (39.5%) cases of H63D mutation (4 homozygous - 4.2%) were found in hemophilia patients which is 1.5-2 times higher than the average incidence of these alleles in the Russian population. For thrombophilia markers frequencies were: F5 - 7 heterozygotes and no homozygotes; MT677 - 36 for the heterozygotes and 9 homozygotes; MT1298 – 35 heterozygotes and 8 homozygotes, and. Twelve patients had heterozygous mutations at the same time for MT677 and MT1298. In patients with hemophilia B, the frequency of homozygous thrombophilia mutations was higher (31.25%) than in hemophilia A (13.3%).
Conclusion
HFE gene mutations may possibly increase the deposition of hemosiderin in the joint tissues subsequently accelerating arthropathy progression. Since 91.4% patients in our sample are infected with viral hepatitis C, hemochromatosis markers may also complicate the course of hepatitis and increase the risk of complications. Homozygous Fokl marker of the vitamin D receptor gene is linked to increased risk of developing infectious complications, therefore in our cohort may increase the risk of purulent postoperative complications. Several alleles of the vitamin D receptor gene are correlated with increased rate of bone resorption and may also increase the risk of aseptic instability in the components of endoprostheses. The presence of thrombophilia markers in patients with hemophilia also may change the course of hemophilia in patients with the same initial level of the deficient factor requiring more individualized approach for hemostatic replacement therapy.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Hemochromatosis, Hemophilia, Thrombophilia
Abstract: PB1806
Type: Publication Only
Background
The intensity and frequency of hemorrhagic manifestations in patients with certain form of hemophilia may vary. There are still no convincing data explaining the different clinical course of hemophilia. Despite comprehensive substitutive hemostatic therapy, some patients develop severe arthropathy requiring surgical support. Frequency of purulent complications after arthroplasty in patients with hemophilia is higher than in the general population.
Aims
To study possible genetic factors that aggravate the course of hemophilia and increase the risk of complications after orthopedic operations.
Methods
96 patients with severe hemophilia and arthropathy who underwent endoprosthesis replacement of the affected joint were included in the study. The mean age was 39.6 years (min 23, max 68): 75 (78.1%) with hemophilia A, 16 (16.7%) with hemophilia B and 5 (5.2%) with an inhibitory form of hemophilia . Histological studies of bone tissue in the area of the affected joint, taken during arthroplasty of the joint, were performed. Patients were examined for antibodies to hepatitis C and hepatitis C RNA. DNA samples were examined for genetic markers of hereditary hemochromatosis (mutations H63D and C282Y of HFE gene), thrombophilia (F5, MT677, MT1298, F2), polymorphisms of the vitamin D receptor gene (Taq1, Apa1 and Fok1) by means of real-time allele-specific polymerase chain reaction.
Results
Homozygous Taql and Apal polymorphisms of the vitamin D receptor gene in hemophilia patients was found in 7.3% and 18.8%, respectively, which corresponds to the literature data for the Russian population. Homozygous Fokl marker was detected in 27 patients (28%), which is 2.8 times more frequent than in general population (10%). Nine heterozygous cases (9.4%) of C282Y HFE gene mutations (none homozygous) and 38 heterozygous (39.5%) cases of H63D mutation (4 homozygous - 4.2%) were found in hemophilia patients which is 1.5-2 times higher than the average incidence of these alleles in the Russian population. For thrombophilia markers frequencies were: F5 - 7 heterozygotes and no homozygotes; MT677 - 36 for the heterozygotes and 9 homozygotes; MT1298 – 35 heterozygotes and 8 homozygotes, and. Twelve patients had heterozygous mutations at the same time for MT677 and MT1298. In patients with hemophilia B, the frequency of homozygous thrombophilia mutations was higher (31.25%) than in hemophilia A (13.3%).
Conclusion
HFE gene mutations may possibly increase the deposition of hemosiderin in the joint tissues subsequently accelerating arthropathy progression. Since 91.4% patients in our sample are infected with viral hepatitis C, hemochromatosis markers may also complicate the course of hepatitis and increase the risk of complications. Homozygous Fokl marker of the vitamin D receptor gene is linked to increased risk of developing infectious complications, therefore in our cohort may increase the risk of purulent postoperative complications. Several alleles of the vitamin D receptor gene are correlated with increased rate of bone resorption and may also increase the risk of aseptic instability in the components of endoprostheses. The presence of thrombophilia markers in patients with hemophilia also may change the course of hemophilia in patients with the same initial level of the deficient factor requiring more individualized approach for hemostatic replacement therapy.
Session topic: 34. Bleeding disorders (congenital and acquired)
Keyword(s): Hemochromatosis, Hemophilia, Thrombophilia