Increased Fibrinogen Levels and Hemostatic Abnormalities in Patients with Arteriolar Nephrosclerosis: Association with Cardiovascular Events

Leonardo A. Sechi; Laura Zingaro; Cristiana Catena; Sergio De Marchi

doi:10.1055/s-0037-1614068

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(04): 565-570
DOI: 10.1055/s-0037-1614068

Review Article

Schattauer GmbH

Increased Fibrinogen Levels and Hemostatic Abnormalities in Patients with Arteriolar Nephrosclerosis: Association with Cardiovascular Events

Leonardo A. Sechi

¹From the Hypertension Unit, Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, Italy

,

Laura Zingaro

¹From the Hypertension Unit, Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, Italy

,

Cristiana Catena

¹From the Hypertension Unit, Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, Italy

,

Sergio De Marchi

¹From the Hypertension Unit, Department of Experimental and Clinical Pathology and Medicine, Chair of Internal Medicine, University of Udine, Udine, Italy

› Author Affiliations

Abstract

Summary

Increased plasma fibrinogen levels and hemostatic abnormalities suggestive of a prothrombotic state are present in patients with endstage renal failure and could contribute to increased cardiovascular morbidity in these patients. We investigated the relationship between abnormalities of the hemostatic system and the degree of renal failure and whether these abnormalities are associated with increased prevalence of cardiovascular events in patients with arteriolar nephrosclerosis. In 425 patients recruited at a hypertension clinic we assessed the renal function by creatinine clearance, urinary protein excretion, and microalbuminuria, the prevalence of atherosclerotic disease, and measured prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, and antithrombin. Early impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m² of body surface area) caused by arteriolar nephrosclerosis was found in 172 patients. Patients with early renal failure were significanly older and had significantly greater values of blood pressure, plasma fibrinogen, F1+2, and D-dimer than patients with normal renal function. Elevated D-dimer and fibrinogen levels were independently associated with the presence of decreased creatinine clearance. Log fibrinogen, log F1+2, and log D-dimer were inversely correlated with creatinine clearance. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was significantly greater in patients with mild renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic disease independent of renal function and other risk factors. In conclusion, changes in hemostatic parameters occur early in the course of renal failure in patients with arteriolar nephrosclerosis, suggesting a prothrombotic state that may contribute to the risk for atherosclerotic disease at all levels of renal function.

Key words

Coagulation - D-dimer - fibrinogen - prothrombin fragment 1+2 - nephrosclerosis - cardiovascular disease

Full Text

References

References
1 Rainer AEG, Margreiter R, Brunner FP, Ehrich JHH, Geelings W, Landais P, Loirat C, Mallik NP, Selwood NH, Tufveson G, Valdebarrano F. Report on the management of renal failure in Europe, XXII, 1991. Nephrol Dial Transplant 1992; 03: 7-35.
2 Lindner A, Charra B, Sherrard DJ, Sribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 1974; 290: 697-701.
3 Jensen T, Stender S, Deckert T. Abnormalities in plasma concentrations of lipoproteins and fibrinogen in type I (insulin-dependent) diabetic patients with increased urinary albumin excretion. Diabetologia 1988; 31: 142-5.
4 Chan MK, Varghese Z, Moorhead JK. Lipid abnormalities in uremia, dialysis and transplantation. Kidney Int 1981; 19: 625-37.
5 Bostom AG, Gohh RY, Beaulieu AJ, Nadeau MR, Hume AL, Jaques PF, Selhub J, Rosenberg IH. Treatment of hyperhomocysteinemia in renal transplant recipients. Ann Intern Med 1997; 127: 1089-92.
6 Parving HH, Smidt UM, Frisberg B, Borrevie-Nielsen V, Andersen AR. A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia 1981; 20: 457-61.
7 London GM, Drueke TB. Atherosclerosis and arteriosclerosis in chronic renal failure. Kidney Int 1997; 51: 1678-95.
8 Tomura S, Nakamura Y, Mayumi D, Ando R, Ida T, Chida Y, Ootsuka S, Shinoda T, Yanagi H, Tsuchia S, Marumo F. Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipids as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 1996; 27: 848-54.
9 Rosenberg RD, Bauer KA. Prothrombin activation fragment assay. Clin Chem 1993; 39: 559-60.
10 Mannucci PM, Giangrande PLF. Detection of prethrombotic state due to procoagulant imbalance. Eur J Haematol 1992; 48: 65-9.
11 Aronson DL, Stevan L, Ball AP, Franza Jr BR, Finlayson JS. Generation of the combined prothrombin activation peptide (F1,2) during the clotting of blood and plasma. J Clin Invest 1977; 60: 1410-8.
12 Graeff H, Hafter R. Detection and relevance of cross linked fibrin derivatives in blood. Semin Thromb Haemost 1982; 08: 57-68.
13 De Marchi S, Cecchin E, Falleti E, Giacomello R, Stel G, Sepiacci G, Bortolotti N, Zanello F, Gonano F, Bartoli E. Long-term effects of erythropoietin therapy on fistula stenosis and plasma concentrations of PDGF and MCP-1 in hemodialysis patients. J Am Soc Nephrol 1997; 08: 1147-56.
14 Malyszko J, Malyszko JS, Pawlak D, Pawlak K, Buczko W, Mysliwiec M. Hemostasis, platelet function and serotonin in acute and chronic renal failure. Thromb Res 1996; 83: 351-61.
15 Irish AB, Thompson CH. The effects of gemfibrozil upon the hypercoagulable state in dyslipidaemic patients with chronic renal failure. Nephrol Dial Transplant 1996; 11: 2223-8.
16 Tomura S, Nakamura Y, Deguchi F, Ando R, Chida Y, Marumao F. Coagulation and fibrinolysis in patients with chronic renal failure undergoing conservative treatment. Thromb Res 1991; 64: 81-90.
17 Vaziri ND, Gonzales EC, Wang J, Said S. Blood coagulation, fibrinolytic, and inhibitory proteins in end-stage renal disease: effect of hemodialysis. Am J Kidney Dis 1994; 23: 828-35.
18 Kannel WB, Wolf PA, Castelli WP, D’Agostino RB. Fibrinogen and risk of cardiovascular disease. JAMA 1987; 258: 1183-6.
19 Irish A. Cardiovascular disease, fibrinogen and the acute phase response: associations with lipids and blood pressure in patients with chronic renal disease. Atherosclerosis 1998; 137: 133-9.
20 Jungers P, Massy ZA, Nguyen TKhoa, Fumeron C, Labrunie M, Lacour B, Descamps-Latscha B, Man NK. Incidence and risk factors of atherosclerotic cardiovascular accidents in predialysis chronic renal failure patients. Nephrol Dial Transplant 1997; 12: 2597-602.
21 Sechi LA, Zingaro L, De Carli S, Sechi G, Catena C, Falleti E, Dell’Anna E, Bartoli E. Increased serum lipoprotein(a) levels in patients with early renal failure. Ann Intern Med 1998; 129: 457-61.
22 Sechi LA, Kronenberg F, De Carli S, Falleti E, Zingaro L, Catena C, Utermann G, Bartoli E. Association of lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension. JAMA 1997; 277: 1689-95.
23 Petrie JC, O’Brien ET, Littler WA, de Swiet M. Recommendations on blood pressure measurement. BMJ 1986; 293: 611-5.
24 The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. 1993 Guidelines for the management of mild hypertension. Memorandum from a World Health Organization/International Society of Hypertension Meeting. Hypertension 1993; 22: 392-403.
25 Sechi LA, Melis A, Tedde R. Insulin hypersecretion: a distinctive feature between essential and secondary hypertension. Metabolism 1992; 11: 1261-6.
26 Rossi E, Lombardi A, Preda L. Method for determination of functional (clottable) fibrinogen by the new family of ACL coagulometers. Thromb Res 1988; 52: 453-68.
27 Pelzer H, Schwarz A, Stuber W. Determination of human prothrombin activation fragment 1+2 in plasma with an antibody against a synthetic peptide. Thromb Haemost 1991; 65: 153-9.
28 Rylatt DB, Blake AS, Cottis LE, Massingham DA, Fletcher WA, Masci PP, Whitaker AN, Elms M, Bunce I, Webber AJ, Wyatt D, Bundesden G. An immunoassay for human D-dimer using monoclonal antibodies. Thromb Res 1983; 31: 767-78.
29 Friedewald WT, Levy RI, Friedrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative centrifuge. Clin Chem 1972; 18: 499-502.
30 Irish GR, Barrantes DM, Ledue TB. Immunoturbidimetry of apolipoprotein B in human serum. Clin Chem 1987; 33: 1267-70.
31 USRDS 1994 Annual Report. Am J Kidney Dis 1994; (24) (Suppl. 02) S88-95.
32 Parfrey PS, Harnett JD. Long-term cardiac morbidity and mortality during dialysis therapy. Adv Nephrol Necker Hosp 1994; 23: 311-30.
33 Meade TW, Mellows S, Brozovic M. Haemostatic function and ischemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-7.
34 Stone MC, Thorp JM. Plasma fibrinogen-a major coronary risk factor. J R Coll Gen Pract 1985; 35: 565-9.
35 Wilhelmsen L, Svardsudd K, Koran-Bengtsen K, Larsson B, Weilin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 11: 501-5.
36 Fowkes FGR, Housley E, Cawood EHH, Macintyre CCA, Ruckley CV, Prescott RJ. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int Epidemiol 1991; 20: 384-92.
37 Dang CV, Bell WR, Shuman M. The normal and morbid biology of fibrinogen. Am J Med 1989; 87: 567-76.
38 Koenig W, Ernst E. Fibrinogen and atherothrombogenesis. Curr Opin Lipidol 1993; 04: 471-6.
39 Folsom AR, Wu KK, Davis CE, Conlan MG, Sorlie PD, Szklo M. Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. Atherosclerosis 1991; 91: 191-205.
40 Krobot K, Heuse HW, Cremer P, Eberle E, Keil U. Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age and sex: results from the second MONICA Augsburg Survey 1989-90. Arterioscler Thromb. 1992; 01 (02) 780-8.
41 Mitropulos KA, Esnouf MP. The prothrombin activation peptide regulates synthesis of the vitamin K-dependent proteins in the rabbit. Thromb Res 1990; 57: 541-59.
42 Franks JJ, Kirsch RE, Frith LOC, Purves LR, Franks WT, Franks SA, Hanson P, Saunders SJ. Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat. J Clin Invest 1981; 67: 575-80.