Clinical, Instrumental, Serological and Histological Findings Suggest That Hemophilia B May be Less Severe Than Hemophilia A

Background: Recent evidences suggest that patients with severe hemophilia B (HB) may have a less severe disease compared to severe hemophilia A (HA).

Objectives: to investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe HA and HB.

Patients/Methods: 70 HA and 35 HB patients with at least one joint bleeding were consecutively enrolled. In all patients were assessed: joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), WFH, Pettersson and ultrasound (US) scores, serum sRANKL and OPG. Expression of RANK, RANKL and OPG was also evaluated in synovial tissue from 18 HA and 4 HB patients. Chi-square test, T-test, Mann-Whitney and Spearman's rank correlation coefficient were performed.

Results: The percentage of patients with either 10-50 or >50 hemarthrosis was greater in HA than in HB (p< 0.001 and p = 0.03, respectively); that with <10 hemarthrosis was higher in HB (p < 0.0001). The mean value of WFH (36.6 vs 20.2;p <0.0001) and US scores (10.9 vs 4.3;p <0.0001) were significantly higher in HA patients. Serum OPG and s RANKL were decreased in HA versus HB (p<0.0001 and p=0.006, respectively) and also in HA patients with>50 hemarthrosis. The expression of OPG was markedly reduced in synovial tissue from HA patients.

Conclusions: The reduced number of hemarthrosis, the lower WFH and US scores and higher OPG levels in serum and expression in synovial tissue in HB suggest that HB is a less severe disease than HA. OPG reduction seems to play a pivotal role in the progression of arthropathy in HA.