Loss of engagement in controlling chronic anticoagulation therapy during Covid-19 stringency measures. A single center experience of disproportioned increase of stuck mechanical valves

Stuck valve is a very rare and severe complication that occurs in mechanical valve replacement patients with ineffective anticoagulation. However, with COVID-19 restriction measures, it became challenging to regularly assess INR to make sure it falls within the target therapeutic range to prevent this complication. We present a series of 10 patients who either underwent transthoracic echocardiography for a suspected stuck valve or were seen at the outpatient valve clinic with the residual consequences of a stuck valve during the COVID-19 restriction measures in our institute. Stuck prosthetic valves incident has increased significantly during this period, particularly those in the mitral position for which urgent replacement and prolonged hospitalization were necessary. Particularly with the COVID-19 restrictions in place, these cases highlight the need for physicians to be aware of the dramatic increase in the incidence of stuck prosthetic valves in patients on chronic warfarin therapy.

Population Pharmacokinetic Modeling and Dose Optimization of Vancomycin in Chinese Patients with Augmented Renal Clearance

Patients with augmented renal clearance (ARC) have been described as having low vancomycin concentration. However, the pharmacokinetic model that best describes vancomycin in patients with ARC has not been clarified. The purpose of this study is to determine the pharmacokinetic of vancomycin in Chinese adults and the recommend dosage for patients with different renal function, including patients with ARC. We retrospectively collected 424 vancomycin serum concentrations from 209 Chinese patients and performed a population pharmacokinetic model using NONMEM 7.4.4. The final model indicated that the clearance rate of vancomycin increased together with the creatinine clearance, and exhibited a nearly saturated curve at higher creatinine clearance. The estimated clearance of vancomycin was between 3.46 and 5.58 L/h in patients with ARC, with 5.58 being the maximum theoretical value. The central volume of distribution increased by more than three times in patients admitted to Intensive Care Unit. Monte Carlo simulations were conducted to explore the probability of reaching the target therapeutic range (24-h area under the curve: 400–650 mg·h/L, trough concentration: 10–20 mg/L) when various dose regimens were administered. The simulations indicated that dose should increase together with the creatinine clearance until 180 mL/min. These findings may contribute to improving the efficacy and safety of vancomycin in patients with ARC.

Prescribing Pattern and Pharmacist Intervention in Anticoagulation at A Tertiary Care Teaching Hospital, Coimbatore, India

Objective: To assess the prescribing pattern and pharmacist intervention in anti-coagulation at a tertiary care teaching hospital, Coimbatore, India Methodology: Data was gathered utilizing a well-structured data collection structure which includes patient's demographics, clinical data which includes (indication for anticoagulation therapy, wanted INR range, anticipated length of therapy, anticoagulation therapy got), social propensities, past medical history, current prescriptions and the prescribed oral anticoagulant (Warfarin/Acitrom). INR values were observed for the patients remembered for the investigation and dosage adjustment was finished by standard convention dependent on the INR value. The patients were also provided with effective counseling regarding the therapy and dietary modifications. All the patients were monitored for any adverse drug events/effects or any possible drug and food interactions during the study period. In case of any reported adverse events/drug associations in the anticoagulation facility, the legitimate intervention was finished by the clinical pharmacist in relationship with a physician to accomplish objective drug therapy. Result: During our study period, 86 patients were forwarded by the physicians to the clinical pharmacist managing the oral anticoagulation clinic. Only 70 patients could complete the study, where 4 patients did not visit the clinic, other 12 patients did not meet the inclusion criteria and hence they are excluded. The data were collected using data collection form for the study sample. After the interventional study, there was a significant improvement in patients maintaining % of INRs which were in target therapeutic range, % of TTR along with decreased adverse effects. It was also found that the patient’s awareness of the target INR values is correlated with the improved accuracy of anticoagulation control. Hence, our study results reflect the need for a clinical pharmacist in oral anticoagulation management and the necessity of implementing anticoagulation services in various hospital settings. Conclusion: the clinical pharmacist managing anticoagulation service was able to achieve the INRs of the patient in to target therapeutic range by proper and timely dose adjustments based on the INR value, to identify adverse drug reactions/ adverse events, drug-drug interactions, and drug-food interactions and bring about proper interventions by working in association with physicians. Keywords: anticoagulant, Clinical pharmacist intervention, INR results, Physician intervention,

P27 Impact of new vancomycin dosing and monitoring guideline

The Neonatal and Paediatric Pharmacists Group (NPPG) released a report which carried out a vancomycin in paediatric audit (VIPA). This report reviewed the effectiveness of currently employed intravenous vancomycin dosing regimens. It stated that British National Formulary for Children (BNFC) vancomycin dosing was not sufficient for achieving the target therapeutic range in typical patients and higher, more frequent dosing is required to reach target levels quicker.1,2Based on this report, we amended our dosing guidelines to the following empirical starting doses for children with normal or mildly impaired renal function:Infant 1–6 months: 10 mg/kg 6 hourlyInfant > 6 month: 15 mg/kg 6 hourlyTo evaluate if the new guidelines achieve target therapeutic levels quicker without increasing toxicity or incidence of adverse effects an audit was carried out. The results were then compared to an audit carried out in 2009 using the old vancomycin pathway which based doses on BNFC dosing of 15 mg/kg every eight hours.3The main objectives were to determine the number of patients that achieved target therapeutic range at steady state, and the dose required to achieve this, the time taken to achieve target therapeutic range, the number of patients that achieved levels <10 mg/L (sub-therapeutic) and >20 mg/L (toxic) and the frequency of adverse effects.MethodData was collected for all patients who had been started on vancomycin from 14th September 2016 to 5th December 2016. Using our electronic prescribing system, a daily report identified patients who had vancomycin prescribed. The data collected was compared to the data collected from the 2009 audit.Results23 patients had been commenced on vancomycin during the audit time frame. 20 of these patients (87%) were started on the correct frequency of 6 hourly dosing, and 13 of these patients (65%) were started on the correct frequency and dose of 15 mg/kg/dose.Of the 13 patients started on the correct dose and frequency, only 6 patients (46%) had their first level taken at the correct time. 4 of these patients (67%) achieved the therapeutic target range of 10–15 mg/L. This has improved from 2009, when an audit completed on the old guidelines showed that 1 patient (7%) reached therapeutic levels without having to adjust dose.No patients’ reached a trough level greater than 20 mg/L and additionally no patients’ had a 50% or greater increase of serum creatinine, suggesting the change to guidelines does not negatively impact on toxicity or acute kidney risk.The mean time to achieve therapeutic dose has decreased from 3.6 days in 2009 to 1.4 days in 2016.There was a correlation between age and vancomycin levels-with the average level for patients between 1–6 months being 10.67 mg/L (therapeutic). Whereas the average vancomycin level for patients over 6 months was 8.14 mg/L (sub- therapeutic). This suggests the new guidelines are more effective for the lower age range group.ConclusionThe new guidelines have helped to achieve target levels quicker, with no increase in toxicity. However, there are still areas for improvement for older paediatric patients; reinforcing the idea of aged based dosing.ReferencesCole C, Shepard M. A review of the trust’s paediatric vancomycin guidelines. Neonatal and Paediatric Pharmacists Group2015;1(1):46. http://adc.bmj.com/content/100/6/e1.50 [Accessed: 22nd August 2016].Nash C, Gooding N, Muller H. Intermittent intravenous vancomycin in children aged over 1 month: Empirical dosing for optimum trough levels. Report to the Neonatal and Paediatric Pharmacist Group January 2016 Neonatal and Paediatric Pharmacists Group2016;1–40. [Accessed: 2nd September 2016].British National Formulary. 2014th–5th ed. BMJ group, Pharmaceutical Press 2015. [Accessed: 2nd September 2016].

Profile and anticoagulation outcomes of patients on warfarin therapy in an urban hospital in Cape Town, South Africa

Background: Warfarin is the most frequently used oral anticoagulant worldwide and it is the oral anticoagulant of choice in South Africa for reducing thrombosis-related morbidity and mortality. However, the safety and efficacy of warfarin therapy depends mainly on careful monitoring and maintenance of the international normalised ratio (INR) within an optimal therapeutic range.Aim: The aim of this study was to describe the profile and the anticoagulation outcomes of patients on warfarin therapy in a major warfarin clinic in the Western Cape Province of South Africa. Setting: Victoria Hospital - a district hospital in Cape Town. Methods: A cross sectional review of clinical records of patients on warfarin therapy who attended the INR clinic from 01 January 2014 to 30 June 2014 was done. Data analysis was done with STATA to generate appropriate descriptive data.Results: Our study showed that atrial fibrillation (AF) was the commonest indication for warfarin use in this study and hypertension was the commonest comorbidity among these patients. Only 48.5% achieved target therapeutic range; 51.5% were out-of-range. There was a significant association between alcohol consumption and poor anticoagulation outcomes (p-value < 0.022). Anticoagulation outcomes were better among the older age groups, male patients and in those with AF. The prevalence of thrombotic events while on warfarin treatment was 2.2%, while prevalence of haemorrhagic events was 14%. Most of the patients with bleeding events were on concurrent use of warfarin and other medications with potential drug interactions.Conclusion: In our study, patients who achieved target therapeutic control were less than the acceptable 60%.Keywords: Oral anticoagulant, anticoagulation outcomes, therapeutic control, percentage INR within target therapeutic range (%ITTR),Time in therapeutic range (TIR)

Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation

SummaryWe performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient’s genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management.Clinical Trials Registration identifier: NCT00993200