Whole blood thrombin generation in Bmal1-deficient mice

Marisa Ninivaggi, Hilde Kelchtermans, Marijke J. Kuijpers, Bianca Hemmeryckx, Johan W. M. Heemskerk, Theo Lindhout, Marc F. Hoylaerts, Bas de Laat*

*Corresponding author for this work

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The Calibrated Automated Thrombogram (CAT) assay that measures thrombin generation (TG) in platelet-poor and -rich plasma, is increasingly being recognised as a more sensitive tool to determine the overall function of the haemostatic system. We developed a method enabling the measurement of TG in a small aliquot of blood. The objective was to validate this assay in mouse blood and to examine the rate and extent of TG in a mouse model of premature aging. TG was assayed in blood from 20 to 28-week-old brain and muscle ARNT-like protein-1 (Bmal1)-deficient (knockout, KO) mice and wild-type (WT) littermates. Bmal1-KO mice are known to display symptoms of premature aging. TG was initiated by adding calcium, tissue factor and a thrombin specific substrate. After TG, the samples were prepared for scanning electron microscopy (SEM). The intra-assay variations (%) in mouse blood of the endogenous thrombin potential (ETP), peak height, lag time, time-to-peak and velocity index were 10% or less (n=24). We found that Bmal1-KO mice have a significantly (p
Original languageEnglish
Pages (from-to)271-275
JournalThrombosis and Haemostasis
Issue number2
Publication statusPublished - Aug 2014


  • Thrombin generation
  • Bmal1-KO mice
  • aging

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