Levels of Tumor Necrosis Factor Alpha and Serum Ferritin in Patients with Hemophilia and Correlation with Clinical Data and Joint Arthropathy

Abstract

Abstract Background Hemophilic arthropathy still represents a major concern especially in resource- limited settings, despite major advances in the management of patients with hemophilia worldwide. TNF-α has been enrolled in the pathophysiology of chronic hemophilic arthropathy. Aim: To evaluate levels of TNF-α and ferritin in patients with hemophilia in relation to hemophilic arthropathy. Methodology We conducted a 6-months comparative cross-sectional study including 38 hemophiliacs with arthropathy (HA+) and without arthropathy (HA−), who are mild, moderate and sever hemophilia; as well as 53 age- and sex-matched healthy control. Patients with a history of acute bleeding or inflammatory conditions in the previous four weeks were excluded from the study. We assessed every patient annual bleeding rate(ABR) measured serum levels of ferritin and TNF-α by using enzyme linked immune-sorbent assay (ELISA). joint status was assessed clinically by the Hemophilia joint health score (HJHS), and radiologically by the six major joints ultrasound (US) Results The median (IQR) age of hemophiliacs was 11.8 (9-16.1) years opposed to 11 (8-13) years in the control group (p = 0.435). Most patients (97.3%) received regular low dose prophylaxis. The median (IQR) HJHS among (HA−) was 0 (0 - 1) versus 18 (9 - 22) in (HA+) group (p < 0.001), and HJHS correlated well with the US score (p < 0.001, p < 0.001 and p = 0.005 for knee, ankle and elbow joints respectively). The annual bleeding rate (ABR) was comparable between both hemophilia groups with median (IQR) 0.88 (0- 2.25) in HA− group versus 1.25 (0.5- 1.75) in HA+ patients (p = 0.571). There was no significant difference in ferritin levels among hemophiliacs with median (IQR) in (HA+) and (HA-) of 40 (35-70) ng/ml and 30 (30-50) ng/ml respectively. On the other hand, TNF-α levels was significantly higher in hemophiliacs compared to control (p < 0.001); with median (IQR) 500 (390 -780) in HA− patients, 485 (385 -580) in HA+ group and 65 (50 - 95) for healthy controls. In a post-hoc analysis TNF-α levels were comparable among patients with and without arthropathy (p = 0.56). Conclusion Hemophiliacs display higher TNF-α levels when compared to healthy controls, which may be a useful surrogate biomarker for bleeding episodes.