Biological variation in tPA-induced plasma clot lysis time

Thromb Haemost. 2012 Oct;108(4):640-6. doi: 10.1160/TH12-02-0124. Epub 2012 Jul 26.


Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.

MeSH terms

  • Adult
  • Aged
  • Air Pollution / adverse effects
  • Analysis of Variance
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Female
  • Fibrin Clot Lysis Time*
  • Fibrinogen / metabolism
  • Humans
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Prothrombin Time
  • Reference Values
  • Risk Factors
  • Thrombin / metabolism
  • Thrombosis / blood
  • Thrombosis / etiology
  • Tissue Plasminogen Activator / administration & dosage
  • Young Adult


  • Biomarkers
  • Inflammation Mediators
  • Fibrinogen
  • C-Reactive Protein
  • Thrombin
  • Tissue Plasminogen Activator