Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

BACKGROUND: Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. OBJECTIVES: To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. METHODS: A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. RESULTS: Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. CONCLUSION: BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.

Capillary compared to venous blood sampling in clozapine treatment: patients׳ and healthcare practitioners׳ experiences with a point-of-care device.

Underuse of the antipsychotic clozapine for schizophrenia is an impediment to improving outcomes for patients. Because of its possible severe side effects, including granulocytopenia or even agranulocytosis, clozapine treatment entails regular WBC monitoring, which can be a major drawback for patients and practitioners. The HemoCue WBC DIFF system is a point-of-care device using capillary blood sampling which provides WBC counts with differentials, including granulocytes. We investigated if capillary sampling instead of conventional venous sampling might diminish the burden for patients and practitioners and motivate them to continue clozapine treatment. A randomized cross-over trial design was used to compare the two sampling methods. Patients׳ subjective experiences of various aspects of blood sampling were rated on a 10-cm visual analogue scale (VAS). Patients and practitioners were also asked if they had any preference for venous or capillary sampling and patients were asked if the sampling method influenced their motivation to continue clozapine treatment. Seventy-three patients were included in this study. Three dropped out before completion. The VAS ratings on all five aspects and the total burden experienced showed a consistent pattern favouring capillary blood sampling (p<0.001). This pattern was more pronounced for inpatients than for outpatients. Patients strongly preferred capillary testing (p<0.001). The method used moderately influenced their motivation for clozapine therapy. In this study patients tolerated capillary blood testing with a point-of-care device better than traditional venous sampling at a laboratory and practitioners also preferred it. Using this method might therefore boost clozapine prescription rates.

Reference values for interleukin-6 and interleukin-8 in cord blood of healthy term neonates and their association with stress-related perinatal factors.

BACKGROUND: Automated interleukin assays are promising diagnostic aids for early-onset neonatal sepsis, however, reference values for healthy term neonates are incompletely known. The goal of this study is to determine reference values for interleukin-6 (IL-6) and interleukin-8 (IL-8) in cord blood of healthy term neonates. METHODS AND FINDINGS: Women were recruited from April 2012 to August 2012. IL-6 and IL-8 levels were measured using an automated immunometric assay (Immulite) in cord blood of 93 healthy term newborns, 60 of them were born via vaginal delivery and 33 by elective caesarean section (ECS). A mean value for IL-8 of 8.1 ± 3.0 pg/mL was found in cord blood of healthy term neonates, which apply to both vaginal delivery and ECS. Regarding IL-6, two values apply. For vaginal delivery, a median value of 3.3 pg/mL (range, <2 to 9.53 pg/mL) was found, while for ECS, a median value of <2 pg/mL (range, <2 to 48 pg/mL) applies. CONCLUSIONS: We propose a reference value of <14.1 pg/mL for IL-8 (mean + 2SD), applying to vaginally delivered and ECS-delivered healthy term newborns. From a clinical point of view, we also propose one reference value for IL-6 to be applied to vaginally delivered and ECS-delivered healthy term newborns, which is <10.2 pg/mL (97.5th percentile total group). These values have to be validated in larger cohorts of neonates, inclusive of those with and without early-onset neonatal sepsis.

Pharmacokinetics of dalteparin during haemodialysis.

BACKGROUND/AIMS: Usually, the appropriate dosage of low-molecular-weight heparin during haemodialysis is empirically based on the clinical effect. We studied the pharmacokinetics of dalteparin during standard haemodialysis in different groups of patients to assess the added value of measuring the anti-Xa activity for dose monitoring and adjustments. METHODS: The pharmacokinetics of intravenously administered dalteparin during haemodialysis was studied in 9 patients during 27 haemodialysis sessions. Six patients received a single bolus dose of dalteparin (group 1), and 3 patients received a higher initial bolus dose of dalteparin followed by a second bolus dose after 2 h (group 2). The clinical effect was evaluated by visual inspection for clot formation in the extracorporeal circuit. RESULTS: The pharmacokinetic curve suggests a zero-order process of elimination. The mean decrease in anti-Xa activity (slope) was comparable in all patients. The mean anti-Xa activity at the end of haemodialysis (Clast) was 0.15 IU/ml in group 1 and 0.60 IU/ml in group 2. CONCLUSION: We conclude that measuring anti-Xa activity can be used to monitor the elimination of dalteparin during haemodialysis and is highly reproducible.

Evaluation of the Ves-Matic Cube 200 erythrocyte sedimentation method: comparison with Westergren-based methods.

The erythrocyte sedimentation rate (ESR) is still a widely used parameter for acute phase inflammation. Recently, new methods based on direct undiluted measurement of ESR in a standard EDTA tube have been developed. We evaluated the analytic performance of one of these new methods, the Ves-Matic Cube 200 (Diesse Diagnostica Senese, Siena, Italy), and compared it with several established Westergren-based diluted methods. The Ves-Matic Cube 200 showed a poor correlation (r = 0.83) with the International Council for Standardization in Haematology Westergren reference method, mainly caused by a considerable negative bias at low ESR levels. Moreover, a random bias was found at higher ESR levels that correlated with hematocrit levels, suggesting a differential influence of packed cell volume on the Ves-Matic Cube 200 results compared with Westergren results. We conclude that the Ves-Matic Cube 200 method is not interchangeable with Westergren-based diluted methods and generates ESR results that are too deviant to be clinically acceptable.