Factor VIII (FVIII) inhibitor antibodies are produced against functional epitopes of FVIII in about 30% of severe hemophilia A patients leading to inhibition of its procoagulant activity. The Bethesda assay, the most commonly used method to measure FVIII inhibitors, based on inhibition of coagulant activity of FVIII, is neither able to detect noninhibitory antibodies nor their isotype. In this study we employed an indirect enzyme-linked immunosorbent assay (ELISA) to measure dif ferent isotypes and IgG subclasses of anti-FVIII anti body in the plasma of hemophiliacs (with and without inhibitor) and normal individuals using recombinant FVIII-coated microtiter plates. The results showed a predominance of IgG and IgG4, though IgA was slightly elevated in a few inhibitor-positive patients and IgM was hardly detectable. A highly significant correlation was found between the Bethesda titer and the optical density values of total Ig, IgG and IgG4 anti-FVIII antibodies obtained by ELISA (p<0.0001). These findings suggest a restricted specificity of anti-FVIII response in hemophiliacs towards functional epitopes of the molecule. Furthermore, high specificity and reasonable sensitivity of the ELISA, together with other technical advantages, suggest this method as a suitable supplementary technique for rapid large-scale screening of inhibitor-positive samples, though ELISA-negative samples need to be rechecked by the Bethesda assay to identify patients with a low inhibitor titer.

Patients with hemophilia suffer from low bone mineral density (BMD) due to several risk factors including arthropathy and resulting immobility. Recent studies have shown variable frequency of low BMD in this group of patients. This study attempts to assess the prevalence of low BMD (osteoporosis and osteopenia) and the associated risk factors in a group of Iranian hemophilia patients. Patients with moderate or severe hemophilia underwent BMD measurement by dual energy X-ray absorptiometry. The results were correlated with other variables including physical activity, calcium intake and demographic data. Forty two patients with the mean age of 31 years (range 18-72) completed the study. The prevalence of osteoporosis in the spine and the left femoral neck was 23.8 and 14.6 %, respectively, and osteopenia in the spine and femoral neck was seen in 45.2 and 31.7 % of the patients, respectively based on the WHO T-score criteria. We found only cigarette smoking to be significantly related to low BMD (P < 0.001). There were two cases of pathologic fracture at femoral neck and forearm (4.8 %). Low BMD is very common in patients with hemophilia. Appropriate assessment of BMD and control of predisposing factors such as prophylactic factor replacement (to prevent hemarthrosis) and cessation of cigarette smoking are warranted.

Biosimilar recombinant activated FVII is found to be as effective as Novoseven in the treatment of acute joint bleeding in patients with hemophilia with inhibitors. Its usage will decrease the gaps in hemophilia.