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Background: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with nonvalvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients. Despite their advantages, concerns persist about a lack of rapid reversal agents in urgent clinical situations. Methods: This review is focused on the pharmacology of nonspecific and target-specific reversal agents for DOACs-induced anticoagulation. A systemic review of preclinical and clinical studies published in peer-reviewed scientific journals was performed. Results and Conclusions: Fresh frozen plasma and coagulation factors concentrates might be considered in bleeding emergencies; however, there is a lack of larger studies confirming the efficacy of coagulation factors concentrates for the reversal of DOACs-induced anticoagulation, and a particular risk of coagulation factors concentrates-induced thrombosis. Recently, idarucizumab has been approved commercially for acute reversal of dabigatran in emergencies as a first target-specific reversal agent. Moreover, andexanet alpha and aripazine are being extensively studied in several phase II and III clinical studies. It is likely that more target-specific agents for reversal of DOACs-induced anticoagulation will be introduced to clinical practice in near future.

Background: Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action. No clinically relevant age- or sex-dependent difference in the apixaban pharmacokinetics and pharmacodynamics which would lead to the modification of the dose exists, apixaban may even be administered with or without food. Its elimination is mediated by metabolism, renal elimination of unmodified drug and excretion in the gastrointestinal tract. Objective: The authors aim to provide a review of currently available literature about apixaban. Method: The authors summed-up the data from the scientific journals related to thrombosis and hemostasis and searched the available databases. Results and Conclusion: Apixaban has many advantages including predictable pharmacokinetics and pharmacodynamics, low number of drug and food interactions, and relatively wide therapeutic window.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial cell-specific mitogen. Expression of VEGF mRNA is increased under hypoxia/ischemia conditions. Its role in the setting of clinical kidney transplantation (Tx) is currently under investigation. Majority of works are dealing with gene polymorphisms and/or renal tissue expression. The aim of the study was to evaluate serum VEGF concentrations after kidney Tx and its relationship to graft outcome. Thirty-five adult patients (17 male, 18 female) treated with cyclosporine A or tacrolimus, at least 1 month after Tx and 22 healthy control (17 male, 5 female). Patients with acute rejection or infection were excluded. Serum VEGF (S-VEGF) concentrations were measured by Quantikine Immunoassay, RD Systems. S-VEGF concentrations were significantly higher after Tx than in healthy control (556 ± 463 pg/ml, vs 145 ± 74 pg/ml, p< 0.0001). No correlation was found with age, gender, time after Tx or type of calcineurin inhibitor. However, a significant correlation was found between basaline S-VEGF and S-creatinine (p< 0.05), S-VEGF and S-creatinine six months after Tx (p< 0.01) and between S-VEGF and cyclosporine toxicity defined as a gingival hyperplasia or biopsy proven nephrotoxicity (202 ± 121 pg/ml in stable patients vs 741 ± 436 pg/ml in cyclosporine toxicity group, p< 0.001). During six months of follow up, the kidney graft function was stable in 100% of patients with S-VEGF concentration ≤ 145 pg/ml but only in 50% of patients with S-VEGF concentration > 145 pg/ml (p < 0,05). We conclude that the S-VEGF concentration seems to be a marker of cyclosporine toxicity and prospective graft function deterioration. S-VEGF could be helpful to select patients who would have benefit from an early switch of immunosuppression.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and endothelial cell-specific mitogen. Expression of VEGF mRNA is increased under hypoxia/ischemia conditions. Its role in the setting of clinical kidney transplantation (Tx) is currently under investigation. Majority of works are dealing with gene polymorphisms and/or renal tissue expression. The aim of the study was to evaluate serum VEGF concentrations after kidney Tx and its relationship to graft outcome. Thirty-five adult patients (17 male, 18 female) treated with cyclosporine A or tacrolimus, at least 1 month after Tx and 22 healthy control (17 male, 5 female). Patients with acute rejection or infection were excluded. Serum VEGF (S-VEGF) concentrations were measured by Quantikine Immunoassay, RD Systems. S-VEGF concentrations were significantly higher after Tx than in healthy control (556 ± 463 pg/ml, vs 145 ± 74 pg/ml, p< 0.0001). No correlation was found with age, gender, time after Tx or type of calcineurin inhibitor. However, a significant correlation was found between basaline S-VEGF and S-creatinine (p< 0.05), S-VEGF and S-creatinine six months after Tx (p< 0.01) and between S-VEGF and cyclosporine toxicity defined as a gingival hyperplasia or biopsy proven nephrotoxicity (202 ± 121 pg/ml in stable patients vs 741 ± 436 pg/ml in cyclosporine toxicity group, p< 0.001). During six months of follow up, the kidney graft function was stable in 100% of patients with S-VEGF concentration ≤ 145 pg/ml but only in 50% of patients with S-VEGF concentration > 145 pg/ml (p < 0,05). We conclude that the S-VEGF concentration seems to be a marker of cyclosporine toxicity and prospective graft function deterioration. S-VEGF could be helpful to select patients who would have benefit from an early switch of immunosuppression.