Download PDF
Thromb Haemost 1994; 71(05): 581-586
DOI: 10.1055/s-0038-1642486
Review Article
Schattauer GmbH Stuttgart

Fibrinogen, D-Dimer and Thrombin-Antithrombin Complexes in a Random Population Sample: Relationships with Other Cardiovascular Risk Factors

Carlo Giansante
The Institute of Clinical Medicine, University of Trieste, Italy
,
Nicola Fiotti
The Institute of Clinical Medicine, University of Trieste, Italy
,
Luigi Cattin
The Institute of Clinical Medicine, University of Trieste, Italy
,
Paolo Giovanni Da Col
The Institute of Clinical Medicine, University of Trieste, Italy
,
Salvatore Calabrese
The Institute of Clinical Medicine, University of Trieste, Italy
› Author Affiliations
Further Information

Publication History

Received 28 April 1993

Accepted after revision 10 January 1994

Publication Date:
26 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Fibrinogen is an independent risk factor for cardiovascular disease and both D-Dimer and Thrombin-Antithrombin complexes may be suitable as laboratory markers of deep venous thrombosis and are becoming more widespread in clinical practice. The aim of our study was to evaluate their normal range and to examine their correlation with various cardiovascular risk factors. Fibrinogen, D-Dimer and Thrombin-Antithrombin complexes were assessed in 516 normal subjects randomly selected from the National Health Service register of Trieste (Italy). In our community the mean value of fibrinogen was 283 ± 71 mg/dl. Fibrinogen increases with age in males and was significantly higher in male smokers. In non-smokers, females had significantly higher fibrinogen values than males. The mean value of D-Dimer was 306 ± 130 ng/ml. In females it is significantly higher. The fibrinogen and D-Dimer correlation coefficient was 0.20 (p < 0.001). The mean level of Thrombin-Antithrombin complexes was 6.25 ±6.8 ng/ml with a distribution markedly skewed towards the left; males had lower concentration than females (p = 0.047). Multiple regression analysis for fibrinogen as a dependent variable showed that D-Dimer, LDL- eholesterol, Body-Mass Index and Thrombin-Antithrombin complexes were poor predictors for fibrinogen plasma levels (R2 = 0.23) and that fibrinogen, ApoAl and age can explain only about 10% of the observed variability in D-Dimer.

 

  • References

  • 1 Ernst E. Plasma fibrinogen - an independent cardiovascular risk factor. J Int Med 1990; 227: 365-72
    CrossrefPubMedGoogle Scholar
  • 2 Fibrinogen Ernst E. An independent risk factor for cardiovascular disease. Br Med J 1991; 303: 596-7
    CrossrefPubMedGoogle Scholar
  • 3 Banerjee AK, Pearson J, Gilliland EL, Goss D, Lewis JD, Stirling Y, Meade TW. A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants. Thromb Haemost. 1992; 68: 261-3
    PubMedGoogle Scholar
  • 4 Merskey C, Gordon H, Lackner H, Schrire V, Kaplan BJ, Sougin-Mibashan R, Nossel HL, Moodie A. Blood coagulation and fibrinolysis in relation to coronary heart disease. A comparative study of normal white men white men with coronary heart disease and normal bantu men. Br Med J 1960; 1: 219-27
    CrossrefPubMedGoogle Scholar
  • 5 Cortellaro M, Boschetti C, Cofrancesco E, Zanussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E. Della Volpe A and the PLAT Study Group The PLAT study: a multidisciplinary study of haemostatic function and conventional risk factors in vascular disease patients. Atherosclerosis 1991; 90: 109-118
    CrossrefPubMedGoogle Scholar
  • 6 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. The Framingham Study. JAMA 1987; 258: 1183-1186
    CrossrefPubMedGoogle Scholar
  • 7 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-537
    PubMedGoogle Scholar
  • 8 Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, Elwood PC. Firbinogen, viscosity and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies. Circulation 1991; 83: 836-844
    CrossrefPubMedGoogle Scholar
  • 9 Meade TW, North WRS, Chakrabarti R, Stirling Y, Haines AP, Thompson SG, Brozovic M. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; i: 1050-1053
    PubMedGoogle Scholar
  • 10 Wilhelmsen L, Svärdsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505
    CrossrefPubMedGoogle Scholar
  • 11 Qizilbash N, Jones L, Warlow C, Mann J. Fibrinogen and lipid concentration as risk factors for transient ischaemic attacks and minor ischaemic strokes. Br Med J 1991; 303: 605-609
    CrossrefPubMedGoogle Scholar
  • 12 Balleisen L, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: I. Baseline data on the relation to age, gender, body-weight, smoking alcohol, pill using and menopause. Thromb Haemost 1985; 54: 475-479
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Balleisen L, Assmann G, Bailey J, Epping PH, Schulte H, van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population: II. Baseline data on the relation to blood pressure blood glucose uric acid and lipid fraction. Thromb Haemost 1985; 54: 721-3
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. J Clin Epidemiol 1990; 43: 913-919
    CrossrefPubMedGoogle Scholar
  • 15 Iso H, Folsom AR, Kenneth KW, Finch A, Munger RG, Sato S, Shimamoto T, Terao A, Komachi Y. Hemostatic variables in Japanese and Caucasian men Plasma fibrinogen factor VIIc, Factor VIIIc and von Willebrand factor and their relations to cardiovascular disease risk factors. Am J Epidemiol 1989; 130: 925-934
    CrossrefPubMedGoogle Scholar
  • 16 Yarnell JWG, Sweetnam PM, Rogers S, Elwood PC, Bainton D, Baker IA, Eastham R, O’Brien JR, Etherington MD. Some long term effects of smoking on the haemostatic system: a report from the Caerphilly and Speedwell collaborative surveys. J Clin Pathol 1987; 40: 909-913
    CrossrefPubMedGoogle Scholar
  • 17 Folsom AR, Wu KK, Davies CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991; 91: 191-205
    CrossrefPubMedGoogle Scholar
  • 18 Ernst E. Regional variations in plasma fibrinogen levels (letter). Ann Intern Med 1991; 115: 329-330
    PubMedGoogle Scholar
  • 19 Prisco D. Markers of increased thrombin generation. Res Clin Lab 1990; 20: 217-25
    PubMedGoogle Scholar
  • 20 Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin- antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost 1988; 59: 101-106
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Bick RL, Baker WF. Diagnostic efficacy of the D-Dimer assay in disseminated intravascular coagulation (DIC). Thromb Res 1992; 65: 785-90
    CrossrefPubMedGoogle Scholar
  • 22 Jørgensen LN, Lind B, Hauch O, Leffers A, Albrecht-Beste E, Konradsen AG. Thrombin-antithrombin III-complex & fibrin degradation products in plasma: surgery and postoperative deep venous thrombosis. Thromb Res 1990; 59: 69-76
    CrossrefPubMedGoogle Scholar
  • 23 Speiser W, Mallek R, Koppensteiner R, Stümpfien A, Kapiotis S, Minar E, Ehringer H, Lechner K. D-Dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness. Thromb Haemost 1990; 64: 196-201
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Heijboer H, Ginsberg JS, Buller HR, Lensing AWA, Colly LP, ten Cate JW. The use of the D-Dimer test in combination with non-invasive testing versus serial non invasive testing alone for the diagnosis of deep-vein thrombosis. Thromb Haemost 1992; 67: 510-3
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Koppensteiner R, Speiser W, Miriar E, Ahmadi R, Ehringer H. D-Dimer in local thrombolytic therapy with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in patients with peripheral arterial occlusive disease. Thromb Haemost 1990; 64: 192-195
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Lawler CM, Bovill EG, Stump DC, Collen DJ, Mann KG, Tracy RP. Fibrin fragment D-Dimer and Bβ peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction. Blood 1990; 75: 1341-8
    PubMedGoogle Scholar
  • 27 Eritsland J, Seljeflot I, Arnesen H, Smith P, Westvik Å. Effects of long treatment with warfarin on fibrinogen, FPA, TAT and D-Dimer in patients with coronary artery disease. Thromb Res 1992; 66: 55-60
    CrossrefPubMedGoogle Scholar
  • 28 Jude B, Amrouni N, Deguine I, Marey A, Asseman P, Watel A, Thery C, Marache P, Cosson A. Coupled D-Dimer and fibrinogen levels during thrombolytic therapy of venous thromboembolism. Thromb Res 1992; 65: 457-462
    CrossrefPubMedGoogle Scholar
  • 29 Estivals M, Pelzer H, Sié P, Pichon J, Boccalon H, Boneu B. Prothrombin fragment 1+2, thrombin-antithrombin III complexes and D-Dimers in acute deep vein thrombosis: effects of heparin treatment. Brit J Haematol 1991; 78: 421-4
    CrossrefPubMedGoogle Scholar
  • 30 Elias A, Bonfils S, Daoud-Elias Gauthier B, Sié P, Boccalon H, Boneu B. Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis. Thromb Haemost 1993; 69: 302-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Tripodi A, Bottasso B, Manucci PM. Elevation of thrombin-antithrombin complexes during thrombolytic therapy in patients with myocardial infarction. Res Clin Lab 1990; 20: 197-202
    PubMedGoogle Scholar
  • 32 Uchiyama T, Matsumoto M, Kobayashi N. Studies on the pathogenesis of coagulopathy with arterial thromboembolism and malignancy. Thromb Res 1990; 59: 955-965
    CrossrefPubMedGoogle Scholar
  • 33 Takahashi H, Tatewaki W, Wada K, Hanano M, Shibata A. Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. Am J Hematol 1990; 33: 90-95
    CrossrefPubMedGoogle Scholar
  • 34 Boneu B, Bes G, Pelzer H, Sié P, Boccalon H. D-Dimers, thrombin antithrombin III complexes and prothrombin fragments 1+2: diagnostic value of clinically suspected deep vein thrombosis. Thromb Haemost 1991; 65: 28-32
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Von Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 17: 237-246
    CrossrefPubMedGoogle Scholar
  • 36 Feruglio GA, Vanuzzo D, Pilotto L, Antonini-Canterin F, Antonini Canterin A, Cigacco GB, Scarpa M, Zerio C, Spanghero M, Marini R, Palmieri M, Moratti P, Cattin L, Da Col PG, Melato M, Valente M. II registro regional delle malattie cardiovascolari del Friuli Venezia Giulia. Lineamenti di uno studio decennale aderente al Progetto Monica dell’ O.M.S. Riv Cardiol Prev e Riab 1988; 6: 55-63
    PubMedGoogle Scholar
  • 37 WHO Monica Project Principal Investigators. The World Health Organization Monica Project (Monitoring trends and determinants in Cardiovascular Disease): a major international collaboration. J Clin Epidemiol 1988; 41: 105-114
    CrossrefPubMedGoogle Scholar
  • 38 Rosengren A, Wilhelmsen L, Welin L, Tsipogianni A, Teger-Nilsson AC, Wedel H. Social influences and cardiovascular risk factors as determinants of plasma fibrinogen concentration in a general population sample of middle aged men. Br Med J 1990; 300: 634-638
    CrossrefPubMedGoogle Scholar
  • 39 Baxter K, Wiseman S, Powell J, Greenhalgh R. Pilot study of a screening test for peripheral arterial disease in middle aged men: fibrinogen as a possible risk factor. Cardiovasc Res 1988; 22: 300-302
    CrossrefPubMedGoogle Scholar
  • 40 Handa K, Kono S, Saku K, Sasaki J, Kawano T, Sasaki Y, Hiroki T, Arakawa K. Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosis. Atherosclerosis 1989; 77: 209-213
    CrossrefPubMedGoogle Scholar
  • 41 Fuller GM, Otto JM, Wolosky BM, McGary GT, Adams MA. The effects of hepatocyte stimulating factor on fibrinogen biosynthesis in hepatocyte monolayers. J Cell Biol 1985; 101: 1481-1486
    CrossrefPubMedGoogle Scholar
  • 42 Gauldie J, Richards C, Harnish D, Landsdorp P, Bowman H. Interferon β/B-Cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Nat Acad Sci USA 1987; 84: 7251-7255
    CrossrefPubMedGoogle Scholar