Solitary CD56+ cells were noted only in the synovial membrane in the study group patients as 0.8 of the cell per HPF. 20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology. Results In our Rigosertib study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16 0.53?ng/ml) compared to the control group (5.85 0.70?ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance. Conclusions This study has exhibited collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target. 1. Introduction The pathophysiology of hemophilia covers a sex-linked inherited coagulation disorder caused by the reduced levels of plasma glycoproteins including the coagulation factor VIII (FVIII) leading to the development of hemophilia A and the analogous reduced levels of coagulation factor IX (FIX) leading to the development of hemophilia B (Christmas disease) [1]. Hemarthrosis consists one of COLL6 the most common complications in the course of congenital coagulation disorders [2]. It is estimated that they account for 70-80% of all hemorrhages in patients with hemophilia [3]. Recurrent clinical and subclinical hemorrhages into the musculoskeletal system lead to the irreversible changes revealing as pain, rigidity, and marked limitation of joint mobility [2, 3]. The syndrome of articular manifestations in the course of hemophilia is known as hemophilic arthropathy (HA) [2]. According to the literature, ~90% of patients with a severe type (FVIII 0.01?IU/ml in serum) of hemophilia A experience hemorrhage Rigosertib with at least one joint bleeding at the age of 4.4 years [4]. The effective prophylactic factor alternative therapy (FRT) is available in many regions of the world, including highly developed countries [3]. However, advanced and fully developed HA still occurs worldwide. In the most severe cases of congenital bleeding disorders, even regular administration of FRT may not prevent the progression of the disease due to the development of plasma inhibitors (anti-FVIII/FIX) against epitopes of appropriate clotting factors [5]. Therefore, addressing the problems of the pathogenesis, prevention, and modern strategies of HA treatment appear to be still justified. There are numerous Rigosertib studies available in the professional literature regarding to the pathophysiology of HA. However, it has not been fully elucidated, especially as regards the pathomechanisms which are associated with the early stage of the disease and, to be more precise, with subclinical early and chronic joint inflammation. The direct presence of extravasated blood in the joint triggers an inflammation which initiates subsequent immunopathological mechanisms [6]. The extravasated blood contains numerous morphotic elements which remain active as regards the secretion of inflammatory mediators including the granulocytes, monocytes, and lymphocytes [7]. Over time, the blood and its related metabolites are progressively assimilated by macrophages (M= 40) which were divided into two consecutive groups enrolled over the two-year period between 2013 and 2015 which were divided into two consecutive groups. The qualification process was based on the medical history, clinical assessment, radiological evaluation, and other supplementary assessments performed before elective total joint replacement medical procedures [21, 22]. All Rigosertib procedures were performed in accordance with the ethical standards of the responsible committee on.