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Effects of dalteparin on anti-Xa activities cannot be predicted in critically ill COVID-19 patients.
van der Heijden, Charlotte D C C; Ter Heine, Rob; Kooistra, Emma J; Brüggemann, Roger J; Walburgh Schmidt, Jesper W J; de Grouw, Elke P L M; Frenzel, Tim; Pickkers, Peter; Leentjens, Jenneke.
  • van der Heijden CDCC; Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Ter Heine R; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
  • Kooistra EJ; Department of Intensive Care, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Brüggemann RJ; Department of Intensive Care, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Walburgh Schmidt JWJ; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
  • de Grouw EPLM; Department of Clinical Chemistry, Radboud University Medical Center, the Netherlands.
  • Frenzel T; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
  • Pickkers P; Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands.
  • Leentjens J; Department of Internal Medicine, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Br J Clin Pharmacol ; 88(6): 2982-2987, 2022 06.
Article in English | MEDLINE | ID: covidwho-1583678
ABSTRACT
Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent randomized trials increased-intensity thromboprophylaxis seemed futile and possibly even harmful. In this explorative pharmacokinetic (PK) study we measured anti-Xa activities on frequent timepoints in 15 critically ill COVID-19 patients receiving dalteparin and performed PK analysis by nonlinear mixed-effect modelling. A linear one-compartment model with first-order kinetics provided a good fit. However, wide interindividual variation in dalteparin absorption (variance 78%) and clearance (variance 34%) was observed, unexplained by routine clinical covariates. Using the final PK model for Monte Carlo simulations, we predicted increased-intensity dalteparin to result in anti-Xa activities well over prophylactic targets (0.2-0.4 IU/mL) in the majority of patients. Therapeutic-intensity dalteparin results in supratherapeutic anti-Xa levels (target 0.6-1.0 IU/mL) in 19% of patients and subtherapeutic levels in 22%. Therefore, anti-Xa measurements should guide high-intensity dalteparin in critically ill COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Venous Thromboembolism / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Br J Clin Pharmacol Year: 2022 Document Type: Article Affiliation country: Bcp.15208

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Venous Thromboembolism / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Br J Clin Pharmacol Year: 2022 Document Type: Article Affiliation country: Bcp.15208