ObjectiveTo explore the clinical characteristics and treatment of hemophilia B with coagulation factor FⅨ inhibitor.
MethodsOn February 8, 2018, one case of child with hemophilia B and FⅨ inhibitor who was admitted to First Affiliated Hospital of Soochow University was selected as research subject into this study. The medical history of the children was collected, coagulation function indicators, plasma coagulation factors, coagulation factor inhibitors and other laboratory tests were conducted, And the diagnosis was made based on the results of above tests and gene sequencing. The child were treated with prednisone (15 mg/d) combined with cyclosporine (50 mg/time×2 times/d) and prednisone (15 mg/d) combined with rapamycin (1.5 mg/d). Treatment efficiency was evaluated by relevant laboratory test results of the child. Follow-up was conducted until September 30, 2019. Clinical characteristics, diagnosis, treatment and curative effect of this case were analyzed retrospectively. The procedure of this study was in accordance with the requirements of the revisedWorld Medical Association Declaration of Helsinkiin 2013.
Results① This child was a 8 years old boy. On February 8, 2018, he was admitted to First Affiliated Hospital of Soochow University due to " repeated joint pain and swelling for 7 years" . The child was diagnosed as severe hemophilia B in May, 2010 at local hospital and received treatment with prothrombin complex and recombinant human FⅨ. The titers of FⅨ inhibitors were 3.2 and 6.2 BU/mL in March and April in 2012, respectively. The child suffered from frequent joint bleeding, and the pain was significantly worse than before. ② After admission, result of routine examination of coagulation function showed activated partial thromboplastin time (APTT) was 165.4 s, prothrombin time (PT) was 13.4 s, thrombin time (TT) was 16.6 s, fibrinogen (FIB) was 3.48 g/L, FⅨ∶C was 0.5%, FⅧ∶C was 20%. The results of revealed APTT were 152.7 and 129.6 s immediately and 2 h later, respectively. Antiphospholipid antibodies and lupus anticoagulant were negative. Titer of hemophilia B inhibitor>10 BU/ml. Genetic sequencing displayed a heterozygous mutation of FⅨ c. 7993C>T (p.Arg29X) in exon 2. ③ The child was diagnosed as severe hemophilia B with FⅨ inhibitor. The child did not achieve improvement after treating with prednisone combined with cyclosporine for 3 months. Then the therapy was adjusted to prednisone combined with rapamycin. Although the change of FⅨ inhibitor titer was not obvious, the frequency of joint hemorrhage was decreased after 6 months of treatment. Nine months later, the titer of FⅨ inhibitor was reduced to 50% of that at first diagnosis, with no recurrence of bleeding. The child achieved partial remission (PR). By the end of the follow-up, the child had no joint swelling or pain, and basically returned to normal life and study.
ConclusionsIt should be alert if patients who diagnose as severe hemophilia B and appear situations such as the frequency of hemorrhage increases after multiple FⅨ infusions and the response to traditional therapy is poor. And titer of FⅨ inhibitor should be detected. Hemophilia B with FⅨ inhibitor is fairly rare, therapeutic efficacy is poor and prone to have adverse reactions. Therefore, correct diagnosis and proper treatment are of great significance to improve hemorrhage of hemophilia B. This conclusion is limited to the clinical analysis of one single case, and it requires to expand sample size for further study and verification.
