Study of environmental and genetic factors determining warfarin toxicity

Background: Warfarin is widely used anticoagulant in treatment and prevention of thrombosis. Despite its common use, warfarin can be associated with bleeding complications because of its narrow therapeutic index. A review of many studies show average yearly rates of warfarin related bleeding as high as 0.5% , 4.9% , 15% for fatal, major, minor bleeding complications. The study is to determine age, gender, pharmacogenetics, drugs influencing warfarin toxicity in Indian patients.Methods: Observational and cross-sectional study was conducted over period of 1 year after obtaining institutional ethics committee permission. Written and informed consent was taken from patients admitted in tertiary care hospital who fulfilled inclusion and exclusion criteria.Results: Most common age for Warfarin toxicity in our study was between 30 to 39 years (22.5%) with mean of 42.9 years. Bleeding risk was higher in elderly with 14 out of 26 patients with age >50 years had bleeding manifestations. Toxicity was more prevalent in female (60%). 40% patients were on drugs interacting with warfarin; NSAIDS (Nonsteroidal Anti-Inflammatary Drug) and antibiotics were the most common interacting drugs. In our study, 17.5% patients had acute liver disease and one patient had deranged creatinine (2.6). 40% of patients had VKORC1 variants and 35% of patients had CYP2C9 variants. Maximum patients developed toxicity within 15-30 days of initiation of warfarin.Conclusions: Warfarin toxicity has multifactorial cause. Drugs and Genetic variation are most common factors influencing warfarin toxicity. Warfarin toxicity has low mortality rate, although it increases with (International Normalised Ratio) INR>10 and with increasing age

Outcome analysis of patients presenting with neurological manifestations of Plasmodium Vivax malaria in tertiary care hospital of Mumbai.

Objective: Plasmodium vivax (P. vivax) infection has been considered for a long time a benign and self-limited disease. Percentage of complicated cases of vivax malaria is on the increasing trend, cerebral malaria being the most dreaded and a potentially life-threatening complication. Material and Methods: A prospective observational study was done after institutional ethics committee approval from July 2011 to February 2012 at tertiary care hospital in Mumbai. We studied the clinical profile and outcome of all the 48 patients above the age of 12 years diagnosed with Cerebral Malaria. Results: Incidence of neurological manifestations of vivax malaria in our hospital was 14.15%, with 32(66.7%) out of 48 patients being males. The mean age of patients with neurological manifestations of vivax malaria was 29.66 years in discharged patients and 50.88 years in expired patients. Altered sensorium 37(77.1%) followed by convulsion 28(58.3%) were common findings, but focal neurological deficit, Bell’s palsy, ataxia, psychosis were also seen. Mortality was higher (62.5%) in patients with premorbid conditions (p value <0.05) and that of with other system involvements (87.5%) including hepatic, renal, hepatorenal, pulmonary involvement (p value<0.05). Association between outcome with older age & high parasite index patients is significant (p value<0.001), however no such significant association was found in terms of gender distribution. Conclusion: Plasmodium vivax, as has been traditionally believed, is no longer a benign species and is causing presentations akin to P. falciparum. It is imperative that clinicians are aware of and ready to handle the complications caused by Plasmodium vivax