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.</p

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

<div><p>Background</p><p>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.</p><p>Objectives</p><p>To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

Incidence rates of bleeding events stratified by time since start of VKA treatment.

<p>Incidence rates of bleeding events stratified by time since start of VKA treatment.</p

Time in therapeutic range per day after starting VKA treatment.

<p>Time in therapeutic range per day after starting VKA treatment.</p

Number of bleeding events stratified by area.

<p>Number of bleeding events stratified by area.</p

Association of TTR with bleeding events.

<p>Association of TTR with bleeding events.</p

Incidence rates of bleeding events stratified by age.

<p>Incidence rates of bleeding events stratified by age.</p

Flow chart of number of individuals included.

<p>Flow chart of number of individuals included.</p

Baseline characteristics.

<p>Baseline characteristics.</p