Thromb Haemost 2001; 85(02): 234-239
DOI: 10.1055/s-0037-1615700
Review Article
Schattauer GmbH

Activation Products of the Haemostatic System in Coronary, Cerebrovascular and Peripheral Arterial Disease

J. G. van der Bom
1   Julius Center for Patient Oriented Research, University Medical Center, Utrecht
2   Gaubius Laboratory TNO-PG, Leiden
,
M. L. Bots
1   Julius Center for Patient Oriented Research, University Medical Center, Utrecht
3   Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
,
F. Haverkate
2   Gaubius Laboratory TNO-PG, Leiden
,
P. Meijer
2   Gaubius Laboratory TNO-PG, Leiden
,
A. Hofman
3   Department of Epidemiology & Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands
,
C. Kluft
2   Gaubius Laboratory TNO-PG, Leiden
,
D. E. Grobbee
1   Julius Center for Patient Oriented Research, University Medical Center, Utrecht
› Author Affiliations
The study was supported by grant # 92.398 from the Netherlands Heart Foundation. Kits for laboratory measurements were supplied by Behringwerke AG, Marburg, Germany.
Further Information

Publication History

Received 15 March 2000

Accepted after resubmission 24 July 2000

Publication Date:
08 December 2017 (online)

Summary

To determine the presence of a ‘hypercoagulable state’ as assessed by indices of thrombin and plasmin generation and of the amount of fibrin that is lysed, in patients with stable coronary, cerebral and peripheral arterial disease a population-based cross-sectional study was performed. From a population-based cohort comprising 7983 men and women aged 55 years and over, we randomly selected 127 subjects with a history of myocardial infarction, 124 with a history of stroke and/or transient ischemic attack, 131 patients with peripheral arterial disease and 263 control subjects in the same age group without arterial disease. Subjects using anticoagulant drugs were not selected. F1+2, TAT, and PAP were not associated with a history of cardiovascular events, nor with peripheral arterial disease. In contrast, positive associations were found for D-Dimer. Mean D-Dimer level was 40 μg/l (95% CI 35,44) in control subjects; 53 μg/l (47, 61) in those with a history of myocar-dial infarction and 51 μg/l (45, 58) in those with a history of stroke and or transient ischemic attack. D-Dimer increased gradually with increasing severity of peripheral atherosclerosis; a decrease in ankle/arm systolic blood pressure ratio of 0.1 was associated with an increase in D-Dimer of 3.9 μg/l (p<0.01). This was more pronounced in subjects with higher F1+2, TAT and PAP concentration. In conclusion, the markers of onset of coagulation F1+2, TAT and PAP are not associated with the presence of arterial disease, but increased levels of these markers are necessary for the positive association between D-Dimer and arterial disease.

 
  • References

  • 1 Grant PJ, Prentice CRM. Coronary artery disease. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. Haemostasis and Thrombosis. Churchill Livingstone; 1994: 1231-54.
  • 2 Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long-term incidence of ischemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342: 1076-79.
  • 3 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group.. Hemostatic factors and risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332: 635-41.
  • 4 Wilhelmsen L, Svardsudd K, Korsan-Bengsten K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5.
  • 5 Tracy RP, Bovill EG, Yanez D, Psaty BM, Fried LP, Heiss G, Lee M, Polak JF, Savage PJ. Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly. Arterioscler Thromb Vasc Biol 1995; 15: 1269-79.
  • 6 Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: insights gained form studies using markers of hemostatic system activation. Blood 1987; 70: 343-50.
  • 7 Hoek JA, Sturk A, Ten Cate JW, Lamping RJ, Berends F, Borm JJ. Laboratory and clinical evaluation of an assay of thrombin-antithrombin III complexes in plasma. Clin Chim 1988; 34: 2058-62.
  • 8 Levi M, de Boer JP, Roem D, ten Cate JW, Hack CE. Plasminogen activation in vivo upon intravenous infusion of DDAVP: quantitative assessment of plasmin-92-antiplasmin complexes with a novel monoclonal antibody based radioimmunoassay. Thromb Haemost 1992; 67: 111-6.
  • 9 Astrup T, Permin TM. Fibrinolysis in the animal Organism. Nature 1947; 159: 681-2.
  • 10 Kienast J, Thompson SG, Raskino C, Pelzer H, Fechtrup C, Ostermann H, van de Loo J. Prothrombin activation fragment 1+2 and thrombin anti-thrombin complexes in patients with angina pectoris: relation to the presence and severity of coronary atherosclerosis. Thromb Haemost 1993; 70: 550-3.
  • 11 Fowkes FGR, Lowe GDO, Housley E, Rattray A, Rumley A, Elton RA, MacGregor IR, Dawes J. Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease. Lancet 1993; 342: 84-6.
  • 12 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. Circulation 1994; 90: 2236-40.
  • 13 Lassila R, Peltonen S, Lepäntalo M, Saarinen O, Kauhanen P, Manninnen V. Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. Arterioscl Thromb 1993; 13: 1738-42.
  • 14 Lee AJ, Fowkes GR, Lowe GDO, Rumley A. Determinants of fibrin d-dimer in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1995; 15: 1094-7.
  • 15 Heinrich J, Schulte H, Schönfeld R, Köhler 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 Haemost 1995; 73: 374-9.
  • 16 Hofman A, Grobbee DE, de Jong PTVM, van den Ouweland FA. Determinants of disease and disabilities in the elderly: the Rotterdam Study. Eur J. Epidemiol 1991; 7: 403-22.
  • 17 Bemmel JH, van, Kors JA. Herpen van G, Methodology for the Modular ECG. Analysis System MEANS. Meth Inform Med 1990; 29: 346-53.
  • 18 Willems JL, Abreu-Lima C, Arnaud P, van Bemmel JH, Brohet C, Degani R, Denis B, Gehring J, Graham I, van Herpen G, Machado H, Macfarlane P, Michaëlis J, Moulopoulos SD, Rubel P, Zywietz C. The diagnostic performance of computer programs for the interpretation of electrocardiograms. N Engl J Med 1991; 325: 1767-73.
  • 19 Bots ML, van der Wilk E, Koudstaal PJ, Grobbee DE. Transient Neurological Attacks in the general population. Prevalence, risk factors and clinical relevance. Stroke 1997; 28: 768-73.
  • 20 Bots ML, van Swieten JC, Breteler MMB, de Jong PTVM, van Gijn J, Hofman A, Grobbee DE. Cerebral white matter lesions and atherosclerosis in the Rotterdam Study. Lancet 1993; 341: 1232-37.
  • 21 van der Bom JG, Bots ML, de Bruijn AM, Hofman A, Grobbee DE. Measurement of β- thromboglobulin in the elderly. Findings from the Rotterdam Study. Fibrinolysis 1994; 8 (Suppl. 02) 157-9.
  • 22 Pancheko E, Dobrovolsky A, Davletov K, Titaeva E, Kravets A, Podinovskaya J, Karpov Y. D-dimer and fibrinolysis in patients with various degrees of atherosclerosis. Eur Heart J 1995; 16: 38-42.
  • 23 De Buyzere M, Philippé J, Duprez D, Baele G, Clement DL. Coagulation system activation and increase of D-dimer levels in peripheral arterial occlusive disease. Am J Hematol 1993; 43: 91-4.
  • 24 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging associated changes in indices of thrombin generation and protein C activation in humans. Normative aging study. J Clin Invest 1987; 80: 1527-34.
  • 25 Giansante C, Fiotti N, Cattin L, Da Coll PG, Calabrese S. Fibrinogen, D-dimer and thrombin- antithrombin complexes in a random population sample: relationships with other cardiovascular disease risk factors. Thromb Haemost 1994; 71: 581-6.
  • 26 Cushman M, Psaty BM, Bovill EG, Cornell ES, Kuller LH, tracey RP.. Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease. Arterioscler Thromb Vasc Biol 1996; 16: 1163-9.
  • 27 Sakkinen PA, Cushman M, Psaty BM, Rodriguez B, Boineau R, Kuller LH, Tracy RP. Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women. Arterioscler Thromb Vasc Biol 1999; 19: 499-504.
  • 28 Cushman M, Lemaitre RN, Kuller LH, Psaty BM, Macy EM, Sharrett AR, Tracy RP. Fibrinolytic activation markers predict myocardial infarction in the elderly. Arterioscler Thromb Vasc Biol 1999; 19: 493-8.
  • 29 Cortellaro M, Cofrancesco E, Boschetti C, Mussoni L, Donati MB, Cardillo M, Catalano M, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Pozzoli E, Turri M. Increased fibrin turnover and high PAI-1 activity as predictors of ischemic events in atherosclerotic patients. Arterioscler Thromb 1993; 13: 1412-17.