Thromb Haemost 2012; 108(04): 640-646
DOI: 10.1160/TH12-02-0124
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Biological variation in tPA-induced plasma clot lysis time

Simone Talens
1   Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
,
Joyce J. M. C. Malfliet
1   Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
,
Goran Rudež
1   Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
,
Henri M. H. Spronk
2   Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
,
Nicole A. H. Janssen
3   Center for Environmental Health, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
,
Piet Meijer
4   ECAT Foundation, Leiden, the Netherlands
,
Cornelis Kluft
4   ECAT Foundation, Leiden, the Netherlands
,
Moniek P. M. de Maat
1   Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
,
Dingeman C. Rijken
1   Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 01 March 2012

Accepted after major revision: 03 July 2012

Publication Date:
29 November 2017 (online)

Summary

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.

 
  • References

  • 1 Reiner AP, Siscovick DS, Rosendaal FR. Hemostatic risk factors and arterial thrombotic disease. Thromb Haemost 2001; 85: 584-595.
  • 2 Rosendaal FR. Risk factors for venous thrombotic disease. Thromb Haemost 1999; 82: 610-619.
  • 3 White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107 (Suppl. 01) I4-8.
  • 4 Talens S, Hoekstra J, Dirkx SP. et al. Proteomic analysis reveals that apolipoprotein A1 levels are decreased in patients with Budd-Chiari syndrome. J Hepatol 2011; 54: 908-914.
  • 5 Meltzer ME, Doggen CJ, de Groot PG. et al. Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men. Blood 2010; 116: 529-536.
  • 6 van Zaane B, Squizzato A, Reuwer AQ. et al. Prolactin and venous thrombosis: indications for a novel risk factor?. Arterioscler Thromb Vasc Biol 2011; 31: 672-677.
  • 7 Lisman T, de Groot PG, Meijers JC. et al. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood 2005; 105: 1102-1105.
  • 8 Guimaraes AH, de Bruijne EL, Lisman T. et al. Hypofibrinolysis is a risk factor for arterial thrombosis at young age. Br J Haematol 2009; 145: 115-120.
  • 9 Lisman T, Leebeek FW, Mosnier LO. et al. Thrombin-activatable fibrinolysis inhibitor deficiency in cirrhosis is not associated with increased plasma fibrinolysis. Gastroenterology 2001; 121: 131-139.
  • 10 Kapiotis S, Jilma B, Quehenberger P. et al. Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex. Circulation 1997; 96: 19-21.
  • 11 Kluft C, Jie AF, Rijken DC. et al. Daytime fluctuations in blood of tissue-type plasminogen activator (t-PA) and its fast-acting inhibitor (PAI-1). Thromb Haemost 1988; 59: 329-332.
  • 12 Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation 1989; 79: 101-106.
  • 13 Undar L, Ertugrul C, Altunbas H. et al. Circadian variations in natural coagulation inhibitors protein C, protein S and antithrombin in healthy men: a possible association with interleukin-6. Thromb Haemost 1999; 81: 571-575.
  • 14 Pinotti M, Bertolucci C, Portaluppi F. et al. Daily and circadian rhythms of tissue factor pathway inhibitor and factor VII activity. Arterioscler Thromb Vasc Biol 2005; 25: 646-649.
  • 15 Rudez G, Meijer P, Spronk HM. et al. Biological variation in inflammatory and hemostatic markers. J Thromb Haemost 2009; 07: 1247-1255.
  • 16 Brook RD, Franklin B, Cascio W. et al. Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 2004; 109: 2655-2671.
  • 17 Dielis AW, Castoldi E, Spronk HM. et al. Coagulation factors and the protein C system as determinants of thrombin generation in a normal population. J Thromb Haemost 2008; 06: 125-131.
  • 18 Rudez G, Janssen NA, Kilinc E. et al. Effects of ambient air pollution on hemostasis and inflammation. Environmental health perspectives 2009; 117: 995-1001.
  • 19 Rijken DC, Hoegee-de Nobel E, Jie AF. et al. Development of a new test for the global fibrinolytic capacity in whole blood. J Thromb Haemost 2008; 06: 151-157.
  • 20 Meltzer ME, Lisman T, de Groot PG. et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116: 113-121.
  • 21 Cellai AP, Lami D, Magi A. et al. Assessment of fibrinolytic activity by measuring the lysis time of a tissue-factor-induced clot: a feasibility evaluation. Clin Appl Thromb Hemost 2010; 16: 337-344.
  • 22 Andreotti F, Davies GJ, Hackett DR. et al. Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. Am J Cardiol 1988; 62: 635-637.
  • 23 Abbate R, Prisco D, Rostagno C. et al. Age-related changes in the hemostatic system. Int J Clin Lab Res 1993; 23: 1-3.
  • 24 Tofler GH, Massaro J, Levy D. et al. Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study). Am J Cardiol 2005; 96: 1280-1283.