ABSTRACT
BACKGROUND: Rivaroxaban has been approved as an antithrombotic agent for prevention of venous thromboembolism with specific indications. At present no antidote is appointed and no guidelines have been formulated for the measurement of Rivaroxaban reversal. OBJECTIVES: In the present study, we have evaluated the influence of prothrombin complex concentrate (PCC) on the anticoagulant effects of Rivaroxaban as measured by prothrombin time (PT) and thrombin generation tests (TGTs). METHODS: Plasma and whole blood samples from healthy volunteers were spiked with Rivaroxaban (up to 800 µg L(-1) ) and PCC was added to these samples in concentration ranges as used clinically to reverse the effects of vitamin K antagonists. PT, endogenous thrombin potential (ETP) and calibrated automated thrombography (CAT) assays were performed with varying tissue factor (TF) concentrations. RESULTS: Addition of PCC to Rivaroxaban-spiked samples did not result in normalization of PT and TGT lag time/T-Lag in ETP and CAT, respectively. In contrast, normalization of ETP and CAT area under the curve did occur. However, the response to PCC addition was strongly TF concentration dependent and in whole blood less PCC was required for Rivaroxaban reversal as compared with plasma. CONCLUSIONS: Prothrombin complex concentrate does not neutralize the lengthening effect on PT and TGT lag time/T-Lag of Rivaroxaban anticoagulated blood in vitro; however, total thrombin potential could be normalized. Response of the different TGTs in this respect is assay condition dependent. Therefore, prospective studies are needed to clarify which assay condition and parameter describes in vivo hemostasis best in patients on Rivaroxaban who are treated with PCC.
Subject(s)
Anticoagulants/antagonists & inhibitors , Blood Coagulation Factors/therapeutic use , Morpholines/antagonists & inhibitors , Morpholines/chemistry , Thiophenes/antagonists & inhibitors , Thiophenes/chemistry , Thrombin/chemistry , Anticoagulants/chemistry , Area Under Curve , Blood Coagulation/drug effects , Blood Coagulation Tests , Calibration , Fibrinolytic Agents/chemistry , Humans , Plasma/drug effects , Prothrombin/chemistry , Prothrombin Time , Rivaroxaban , Thromboplastin/chemistry , Time Factors , Vitamin K/antagonists & inhibitorsSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Coagulation/drug effects , Cell-Derived Microparticles/drug effects , Granulocyte Precursor Cells/drug effects , Leukemia, Myeloid, Acute/drug therapy , Thrombin/metabolism , Thrombosis/etiology , Adult , Biomarkers/blood , Blood Coagulation Tests , Cell-Derived Microparticles/metabolism , Female , Flow Cytometry , Granulocyte Precursor Cells/immunology , Granulocyte Precursor Cells/metabolism , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/immunology , Leukocyte Count , Male , Middle Aged , Thrombosis/blood , Thrombosis/immunology , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: A limited number of psychotherapy sessions in combination with medication is preferable to pharmacotherapy only in the treatment of ambulatory patients with major depression. Whether there is a relation between the number of sessions and the efficacy of the treatment is uncertain. METHOD: Randomized clinical trial comparing two treatment conditions in outpatients with major depression. All patients studied had a baseline score of at least 14 points on the 17-item Hamilton Depression Rating Scale. The two conditions consist of 8-session or 16-session Short Psychodynamic Supportive Psychotherapy, both in combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS, the CGI of Severity and of Improvement, the depression subscale of the SCL-90 and the Quality of Life Depression Scale. RESULTS: The rate of change would seem to indicate that eight sessions are preferable for both moderately and severely depressed patients, although the results converged again at the end. Furthermore, in terms of satisfaction with the number of sessions and drop-out percentages during treatment, no differences were found between the conditions. CONCLUSION: In the light of the outcome analysis (faster remission after fewer sessions), a short version of the psychotherapy treatment in a combined course of treatment seems to be justified.
