The clinical presentation, magnitude and risk factors for development of inhibitors of factor viii and ix among patients with Hemophilia at Muhimbili National Hospital

Abstract

Background: Inhibitor development continues to be a severe complication worldwide in hemophilia patients on factor replacement therapy. Given the difficulties associated with the treatment of inhibitors in both the developed and the developing world, prediction and prevention of inhibitors following exposure to factor VIII or IX in hemophilia patients has become a management priority. Objective: To determine the magnitude, clinical presentation and risk factors of factor VIII and IX inhibitors in hemophiliac patients at Muhimbili National Hospital (MNH) Methodology: A descriptive cross sectional study, involved hemophilia cohort attending MNH. It involved patients in hemophilia registry in MNH which were comprised of 77 patients. Among 77 patients in the registry, only 60 patients had complete details. Forty seven hemophilia A and 13 hemophilia B. Patients were recruited between August 2016 and February 2017. Activated Partial Thromboplastin Time (APTT) was performed to pooled patients plasma with normal activated prothrombin time (23-30 seconds) and hemophiliac patient’s plasma. Equal plasmas volume mixing of normal and hemophiliac patient was also done and APTT performed by using automated coagulation analyzer to determine presence of immediate inhibitors. After 2hours at 37 degrees centigrade incubation of normal, hemophiliac patient plasma and a mixture of both, APTT for time dependent factors inhibitors (FVIII) was obtained. The collected data was analyzed using SPSS software version 20.0. Results: Sixty (60) patients with hemophilia were recruited, 78.3% with hemophilia A and 21.7% hemophilia B. The mean age at diagnosis was 6.6 ± 5.9 years while the mean age at interview being 12.9 ± 7.2 years. Majority of patients were at primary and secondary school by 36.7% and 31.7% respectively. Although hemophilia patients are widely distributed in all regions of Tanzania, 51.7% of patients recruited in the study were residents of Dar es Salaam. The prevalence of inhibitors was found to be 6.7% in all hemophiliac patients recruited in the study. Among hemophilia A patients, the prevalence of inhibitors was found to be 8.5%. The prevalence of inhibitors was found to be 15.4% in severe hemophilia A. Hemarthrosis was the frequent clinical feature 45.0%, at the time of diagnosis and 35.0% at the time of interview followed by hematoma 10.0% and 16.7% at diagnosis and interview respectively. Fifty percent (50%) of hemophilia A patients with inhibitors had a family history of uncontrolled bleeding despite the respective dose of factor eight (FVIII) concentrate which was suggestive of genetic predisposition. 3.6% had <50 doses of factor concentrate develop inhibitors while 40% had been exposed to factor concentrate>50doses developed inhibitors. Conclusion: The prevalence of hemophilia inhibitors was high in severe hemophilia A attending MNH. The most common symptoms was hemarthrosis followed by hematoma. Majority of hemophilia study population had been exposed to factor concentrates less than 50 doses during the course of illness.