Evaluation of pre-analytical, demographic, behavioural and metabolic variables on fibrinolysis and haemostasis activation markers utilised to assess hypercoagulability
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Mojca Stegnar
Abstract
Background: Measurement of some haemostatic factors and products formed during activation of haemostasis seems to be promising in the determination of hypercoagulability.
Methods: The fibrinolytic variables euglobulin clot lysis time, tissue-type plasminogen activator, plasminogen activator inhibitor-1 and the haemostasis activation markers prothrombin fragment 1+2, thrombin-antithrombin complex and D-dimer were determined in 101 apparently healthy men and women aged 20–92 years (58±18 years, mean±SD) to establish variability due to several demographic, behavioural and metabolic factors.
Results: None of the fibrinolytic variables were affected by smoking, while tissue-type plasminogen activator antigen was significantly lower in women compared to men. Multiple regression analysis revealed several independent associations between tissue-type plasminogen activator, plasminogen activator inhibitor, body mass index and lipid levels, describing up to 40% of the variance in fibrinolytic variables. For haemostasis activation markers, no gender difference or effect of smoking was observed. Only D-dimer was independently associated with age. The haemostasis activation markers determined proved to be extremely sensitive to blood sampling procedure and were significantly higher in samples obtained by an untrained nurse compared to a trained nurse.
Conclusions: Fibrinolytic variables are predominantly modulated by age, body mass index and blood lipids, while haemostasis activation markers are mainly un-influenced by these factors.
Clin Chem Lab Med 2007;45:40–6.
References
1. Bauer KA. Laboratory markers of coagulation activation. Arch Pathol Lab Med1993;117:71–7.Suche in Google Scholar
2. Haeberli A. Prothrombin fragment F1+2. In: Jespersen J, Bertina RM, Haverkate F. Laboratory techniques in thrombosis – a manual. Dordrecht: Kluwer, 1999:217–22.Suche in Google Scholar
3. Lau HK, Rosenberg RD. The isolation and characterization of a specific antibody population directed against the thrombin antithrombin complex. J Biol Chem1980;255:5885–93.10.1016/S0021-9258(19)70713-3Suche in Google Scholar
4. Hoffmeister HM, Heller W, Seipel L. Activation markers of coagulation and fibrinolysis: alterations and predictive value in acute coronary syndromes. Thromb Haemost1999;82(Suppl 1):76–9.10.1055/s-0037-1615559Suche in Google Scholar
5. Meade TW, Cooper JA, Chakrabarti R, Miller GJ, Stirling Y, Howarth DJ. Fibrinolytic activity and clotting factors in ischaemic heart disease in women. Br Med J1996;312:1581.10.1136/bmj.312.7046.1581aSuche in Google Scholar
6. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study. Lancet1993;342:1076–9.10.1016/0140-6736(93)92062-XSuche in Google Scholar
7. Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Hennekens CH. Endogenous tissue-type plasminogen activator and risk of myocardial infarction. Lancet1993;341:1165–8.10.1016/0140-6736(93)90998-VSuche in Google Scholar
8. Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, et al. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet1987;2:3–9.10.1016/S0140-6736(87)93050-9Suche in Google Scholar
9. Wiman B. Plasminogen activator inhibitor 1 (PAI-1) in plasma: its role in thrombotic disease. Thromb Haemost1995;74:71–6.10.1055/s-0038-1642655Suche in Google Scholar
10. Grimaudo V, Bachmann F, Hauert J, Christe MA, Kruithof EK. Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. Thromb Haemost1992;67:397–401.10.1055/s-0038-1648459Suche in Google Scholar
11. Crowther MA, Roberts J, Roberts R, Johnston M, Stevens P, Skingley P, et al. Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study. Thromb Haemost2001;85:390–4.10.1055/s-0037-1615594Suche in Google Scholar
12. Schulman S, Wiman B. The significance of hypofibrinolysis for the risk of recurrence of venous thromboembolism. Duration of Anticoagulation (DURAC) Trial Study Group. Thromb Haemost1996;75:607–11.10.1055/s-0038-1650330Suche in Google Scholar
13. Ridker PM, Vaughan DE, Stampfer MJ, Manson JE, Shen C, Newcomer LM, et al. Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor. Circulation1992;85:1822–7.10.1161/01.CIR.85.5.1822Suche in Google Scholar
14. Lisman T, de Groot PG, Meijers JC, Rosendaal FR. Reduced plasma fibrinolytic potential is a risk factor for venous thrombosis. Blood2005;105:1102–5.10.1182/blood-2004-08-3253Suche in Google Scholar
15. van der Bom JG, Bots ML, Haverkate F, Meijer P, Hofman A, Kluft C, et al. Activation products of the haemostatic system in coronary, cerebrovascular and peripheral arterial disease. Thromb Haemost2001;85:234–9.10.1055/s-0037-1615700Suche in Google Scholar
16. Ridker PM, Hennekens CH, Cerskus A, Stampfer MJ. Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. Circulation1994;90:2236–40.10.1161/01.CIR.90.5.2236Suche in Google Scholar
17. Fowkes FG, Lowe GD, Housley E, Rattray A, Rumley A, Elton RA, et al. Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease. Lancet1993;342:84–6.10.1016/0140-6736(93)91288-WSuche in Google Scholar
18. Koenig W, Rothenbacher D, Hoffmeister A, Griesshammer M, Brenner H. Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results of a large case-control study. Arterioscler Thromb Vasc Biol2001;21:1701–5.10.1161/hq1001.097020Suche in Google Scholar PubMed
19. Lowe GD, Rumley A, Sweetnam PM, Yarnell JW, Rumley J. Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic heart disease in the caerphilly study. Thromb Haemost2001;86:822–7.10.1055/s-0037-1616138Suche in Google Scholar
20. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, et al. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation2001;103:2323–7.10.1161/01.CIR.103.19.2323Suche in Google Scholar
21. Gaffney PJ, Creighton LJ, Perry MJ, Callus M, Thorpe R, Spitz M. Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). I. Characterization and preliminary evaluation in plasma. Br J Haematol1988;68:83–90.10.1111/j.1365-2141.1988.tb04183.xSuche in Google Scholar PubMed
22. Reber G, de Moerloose P. D-dimer assays for the exclusion of venous thromboembolism. Semin Thromb Hemost2000;26:619–24.10.1055/s-2000-13217Suche in Google Scholar PubMed
23. Heinrich J, Schulte H, Schonfeld R, Kohler E, Assmann G. Association of variables of coagulation, fibrinolysis and acute-phase with atherosclerosis in coronary and peripheral arteries and those arteries supplying the brain. Thromb Haemost1995;73:374–9.10.1055/s-0038-1653783Suche in Google Scholar
24. Folsom AR, Aleksic N, Park E, Salomaa V, Juneja H, Wu KK. Prospective study of fibrinolytic factors and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb Vasc Biol2001;21:611–7.10.1161/01.ATV.21.4.611Suche in Google Scholar
25. Stegnar M, Peternel P, Keber D, Vene N. Poor fibrinolytic response to venous occlusion by different criteria in patients with deep vein thrombosis. Thromb Res1991;64:445–53.10.1016/0049-3848(91)90345-WSuche in Google Scholar
26. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem1972;18:499–502.10.1093/clinchem/18.6.499Suche in Google Scholar
27. MacCallum PK, Cooper JA, Howarth DJ, Meade TW, Miller GJ. Sex differences in the determinants of fibrinolytic activity. Thromb Haemost1998;79:587–90.10.1055/s-0037-1614950Suche in Google Scholar
28. Stegnar M, Pentek M. Fibrinolytic response to venous occlusion in healthy subjects: relationship to age, gender, body weight, blood lipids and insulin. Thromb Res1993;69:81–92.10.1016/0049-3848(93)90005-9Suche in Google Scholar
29. Aillaud MF, Pignol F, Alessi MC, Harle JR, Escande M, Mongin M, et al. Increase in plasma concentration of plasminogen activator inhibitor, fibrinogen, von Willebrand factor, factor VIII:C and in erythrocyte sedimentation rate with age. Thromb Haemost1986;55:330–2.10.1055/s-0038-1661557Suche in Google Scholar
30. Ranby M, Bergsdorf N, Nilsson T, Mellbring G, Winblad B, Bucht G. Age dependence of tissue plasminogen activator concentrations in plasma, as studied by an improved enzyme-linked immunosorbent assay. Clin Chem1986;32:2160–5.10.1093/clinchem/32.12.2160Suche in Google Scholar
31. Mussoni L, Baldassarre D, Mannucci L, Sirtori CR, Tremoli E. Relationship between fibrinolytic and metabolic variables: a study in patients attending a lipid clinic. Ann Med2000;32:134–41.10.3109/07853890009011763Suche in Google Scholar PubMed
32. De Pergola G, Pannacciulli N. Coagulation and fibrinolysis abnormalities in obesity. J Endocrinol Invest2002;25:899–904.10.1007/BF03344054Suche in Google Scholar PubMed
33. Wiman B. The role of the fibrinolytic system in thrombotic disease. Acta Med Scand Suppl1987;715:169–71.10.1111/j.0954-6820.1987.tb09918.xSuche in Google Scholar PubMed
34. Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrieres J, et al. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction – the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost1998;80:749–56.10.1055/s-0037-1615353Suche in Google Scholar
35. Declerck PJ, Alessi MC, Verstreken M, Kruithof EK, Juhan-Vague I, Collen D. Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunosorbent assay. Blood1988;71:220–5.10.1182/blood.V71.1.220.220Suche in Google Scholar
36. Booth NA, Simpson AJ, Croll A, Bennett B, MacGregor IR. Plasminogen activator inhibitor (PAI-1) in plasma and platelets. Br J Haematol1988;70:327–33.10.1111/j.1365-2141.1988.tb02490.xSuche in Google Scholar PubMed
37. Kruithof EK, Nicolosa G, Bachmann F. Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation. Blood1987;70:1645–53.10.1182/blood.V70.5.1645.1645Suche in Google Scholar
38. Juhan-Vague I, Alessi MC, Vague P. Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia1991;34:457–62.10.1007/BF00403280Suche in Google Scholar PubMed
39. Juhan-Vague I, Alessi MC, Mavri A, Morange PE. Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost2003;1:1575–9.10.1046/j.1538-7836.2003.00279.xSuche in Google Scholar PubMed
40. Greenberg CS, Hursting MJ, Macik BG, Ortel TL, Kane WH, Moore BM. Evaluation of preanalytical variables associated with measurement of prothrombin fragment 1.2. Clin Chem1994;40:1962–9.10.1093/clinchem/40.10.1962Suche in Google Scholar
41. Becker RC, Bovill EG, Seghatchian MJ, Samama MM. Pathobiology of thrombin in acute coronary syndromes. Am Heart J1998;136:S19–31.10.1053/hj.1998.v136.93435Suche in Google Scholar PubMed
42. Lippi G, Salvagno GL, Montagnana M, Brocco G, Guidi GC. Influence of short-term venous stasis on clinical chemistry testing. Clin Chem Lab Med2005;43:869–75.10.1515/CCLM.2005.146Suche in Google Scholar PubMed
43. Yarnell JW, Sweetnam PM, Rumley A, Lowe GD. Lifestyle factors and coagulation activation markers: the Caerphilly Study. Blood Coagul Fibrinolysis2001;12:721–8.10.1097/00001721-200112000-00015Suche in Google Scholar PubMed
44. Hursting MJ, Stead AG, Crout FV, Horvath BZ, Moore BM. Effects of age, race, sex, and smoking on prothrombin fragment 1.2 in a healthy population. Clin Chem1993;39:683–6.10.1093/clinchem/39.4.683Suche in Google Scholar
45. Lowe GD, Rumley A, Woodward M, Morrison CE, Philippou H, Lane DA, et al. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use. Br J Haematol1997;97:775–84.10.1046/j.1365-2141.1997.1222936.xSuche in Google Scholar PubMed
46. Woodward M, Lowe GD, Rumley A, Tunstall-Pedoe H, Philippou H, Lane DA, et al. Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol1997;97:785–97.10.1046/j.1365-2141.1997.1232935.xSuche in Google Scholar PubMed
47. Lee AJ, Fowkes GR, Lowe GD, Rumley A. Determinants of fibrin D-dimer in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol1995;15:1094–7.10.1161/01.ATV.15.8.1094Suche in Google Scholar PubMed
©2007 by Walter de Gruyter Berlin New York
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- CCLM: Bringing advances in laboratory medicine to the “New World”
- Diagnostic approach to inherited bleeding disorders
- Linking laboratory and medication data: new opportunities for pharmacoepidemiological research
- Association between polymorphisms of ACE, B2AR, ANP and ENOS and cardiovascular diseases: a community-based study in the Matsu area
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