ABSTRACT
AIM: Warfarin is a widely used anticoagulant for the prevention and treatment of thromboembolism. We conducted a retrospective review to determine the causes and management of warfarin toxicity of patients admitted to Tygerberg hospital between June 2014 and June 2015. RESULTS: We identified and evaluated 126 patients who met the inclusion criteria. The cause of warfarin toxicity was identified and addressed in only 14.3% (18/126) of patients. Where the cause was identified, 56% (10/18) was due to dosing errors and 17% (3/18) drug-drug interaction (DDI). However, 77% (97/126) of patients were retrospectively identified as receiving concomitant medicines known to interact with warfarin at the time of admission. Twenty-eight percent (35/126) of patients presented with major bleeding, which included seven cases of intracranial haemorrhage. Patients were admitted for a median of eight days at an average treatment cost of R10 578. CONCLUSION: We found that warfarin toxicity carries significant mortality and cost, but little attention is paid to the causes of toxicity.
Subject(s)
Anticoagulants/adverse effects , Blood Coagulation/drug effects , Hemorrhage/chemically induced , Tertiary Care Centers , Warfarin/adverse effects , Aged , Anticoagulants/administration & dosage , Drug Costs , Drug Interactions , Female , Hemorrhage/economics , Hemorrhage/mortality , Hemorrhage/therapy , Hospital Costs , Humans , International Normalized Ratio , Length of Stay , Male , Medication Errors , Middle Aged , Polypharmacy , Preliminary Data , Retrospective Studies , Risk Factors , South Africa , Time Factors , Treatment Outcome , Warfarin/administration & dosageABSTRACT
The DEAD box RNA helicase, p68, has been implicated in various cellular processes and has been shown to possess transcriptional coactivator function. Here, we show that p68 potently synergises with the p53 tumour suppressor protein to stimulate transcription from p53-dependent promoters and that endogenous p68 and p53 co-immunoprecipitate from nuclear extracts. Strikingly, RNAi suppression of p68 inhibits p53 target gene expression in response to DNA damage, as well as p53-dependent apoptosis, but does not influence p53 stabilisation or expression of non-p53-responsive genes. We also show, by chromatin immunoprecipitation, that p68 is recruited to the p21 promoter in a p53-dependent manner, consistent with a role in promoting transcriptional initiation. Interestingly, p68 knock-down does not significantly affect NF-kappaB activation, suggesting that the stimulation of p53 transcriptional activity is not due to a general transcription effect. This study represents the first report of the involvement of an RNA helicase in the p53 response, and highlights a novel mechanism by which p68 may act as a tumour cosuppressor in governing p53 transcriptional activity.
