The investigation of relationship between joint findings and serum angiogenic and inflammatory factor levels in severe hemophilia A patients

Despite the use of early prophylactic Factor VIII replacement in severe hemophilia A patients, bleeding into joints cannot be prevented completely and permanent joint damage remains to occur as a result. Early diagnosis and treatment of the joint bleeedings are important for prevention of permanent joint damage. Today, the early detection of the joint bleeding at the beginning of the episode is not possible with clinical signs and current labarotory and radiologic imaging methods. Recent studies have shown that neoangiogenesis plays important role in development of synovitis after recurrent joint bleedings and the histological abnormalities and findings of neoangiogenesis in hemophiliac arthropathy are similar to those in other joint diseases. This study aimed to investigate the relationship between joİnt findings and levels of plasma angiogenic and inflammatory factors in severe hemophilia A patients.Severe, inhibitor negative, hemophilia A patients from four hemophilia centers were included into the study. The patient groups consisted of 10 severe hemophilia A patients withacute joint bleeding and joint damage and 25 severe hemophilia A patients with no acute joint bleeding (with joint damage or not). The control group consisted of 22 healthy male children.Each group of patients were further subdivided into two groups with respect to degree of joint damage as presence of joint damage and presence of severe joint damage. Complete bloodcount analysis, C-reactive protein (CRP), serum ferritin, lactic acid and ELISA based detection of vascular endhotelial growth factor (VEGF), intercellular adhesion molecule-1, thrombomodulin (TM), macrophage inhibitory factor (MIF), and endostatin were performed from peripheral blood of patient and the control groups. The joint findings of hemophilia A patients were evaluated clinically by hemophilia joint health score and radiologically by Petterson scoring and Denver magnetic resonance imaging scoring methods.Serum ferritin, CRP and lactic acid levels were found to be increased in hemophilia A patients compared to the control group. CRP was significantly increased in hemophilia patients with joint damage compared to hemophiliacs with no joint damage. The increase in levels of CRP and MIF were detected significantly higher in patients with acute joint bleeding. There was a positive correlation between serum TM and VEGF and MIF levels.The finding of increased levels of CRP and MIF in acute bleeding supports the presence of bleeding regardless of the degree of the joint damage. The present findings show that investigation of the levels of these angiogenic factors in large number of severe hemophilia A patients with acute bleeding episodes may give further information about early joint damage.Key words: Angiogenesis, hemarthrosis, hemophilia