Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty

Purpose:Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty.ABCB1 is a key gene in the metabolism of dabigatran etexilate.Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.Methods:The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty.Patients with anemia and coagulation disorders,elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study.The association of ABCB1 gene polymorphisms rs1128503,rs2032582,rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a realtime polymerase chain reaction assay and laboratory blood tests.The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers.The probability of the type 1 error(p)was less than 0.05 was considered statistically significant.BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests.All calculations were performed using Rprogramming language v3.6.3.Results:For all polymorphisms there was no association with the level of platelets,protein,creatinine,alanine transaminase,prothrombin,international normalized ratio,activated partial thromboplastin time and fibrinogen.Carriers of rs1128503(TT)had a significant decrease of hematocrit(p=0.001),red blood count and hemoglobin(p=0.015)while receiving dabigatran therapy during the postoperative period compared to the CC,CT.Carriers of rs2032582(TT)had a significant decrease of hematocrit(p=0.001),red blood count and hemoglobin(p=0.006)while receiving dabigatran therapy during the postoperative period compared to the GG,GT phenotypes.These differences were not observed in carriers of rs4148738.Conclusion:It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503(TT)or rs2032582(TT)polymorphisms in favor of other new oral anticoagulants.The longterm implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Human bone graft cytocompatibility with mesenchymal stromal cells is comparable after thermal sterilization and washing followed byγ-irradiation:an in vitro study

Human bone allografts present a better alternative to autografts in terms of minimization of the harvesting procedure complications.Prior to the use in clinical applications,they require sterilization which aims to reduce bioburden.This often comes at the expense of their biological properties as carriers of cells.In this study,we evaluated the cytocompatibility of human bone allografts processed and sterilized by three different methods withmesenchymal stromal cells.Bone morphology,biological and biochemical properties of the extracted bone-conditionedmedium and viability of cells were assessed.We found that chemical sterilization had a strong negative effect on cell viability,whereas thermal sterilization and washing with subsequentγ-irradiation both resulted in a bone graft compatible with the progenitor cells.Moreover,washing of the bone prior to sterilization allowed solid removal of cell debris and other bone marrow components.Taken together,our findings demonstrate the importance of a proper choice of the bone graft processing method for the production of the biomaterial suitable for tissue engineering.