Thromb Haemost 2008; 99(01): 169-173
DOI: 10.1160/TH07-08-0484
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Persistent hyperfibrinogenemia in acute ischemic stroke / transient ischemic attack (TIA)

Shani Shenhar-Tsarfaty
1   Department of Neurology
,
Einor Ben Assayag
1   Department of Neurology
,
Irena Bova
1   Department of Neurology
,
Ludmila Shopin
1   Department of Neurology
,
Michael Cohen
2   Department of Medicine 'D', Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Shlomo Berliner
2   Department of Medicine 'D', Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Itzhak Shapira
2   Department of Medicine 'D', Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Natan M Bornstein
1   Department of Neurology
› Author Affiliations
Further Information

Publication History

Received: 02 August 2007

Accepted after major revision: 12 November 2007

Publication Date:
24 November 2017 (online)

Summary

Increased fibrinogen concentration is a well known phenomenon following acute ischemic stroke. However, the natural course of this hyperfibrinogenemia is uncertain. We aimed to clarify whether it is of a transient or more persistent nature in patients who harbor an underlying morbid biology of atherothrombo-inflammation. Venous blood for fibrinogen measurements was obtained from the control group participants and from stroke patients within 24 hours of admission, as well as 12 months following the acute event. In order to perform a time course analysis, we divided our cohort into tiles of time from symptoms' onset and compared the fibrinogen concentrations usingANOVA. Elevated fibrinogen concentrations were found in stroke patients on admission compared with matched controls (p<0.001).Analysis of variance in the different tertiles of time from symptoms' onset identified that fibrinogen concentrations were already relatively high during the initial phase of the event and did not differ significantly between the tiles (p=0.268). Moreover, when we calculated the absolute differences between the patients' fibrinogen concentrations and that of the matched controls there was clearly a minor increment during the time course from symptoms' onset in the stroke patients group. In conclusion, persistent hyperfibrinogenemia is present in patients with acute ischemic cerebral events and it might be present during the earlier stages of the disease as presently shown. Prompt and longterm, rather than short term, interventions to reduce the concentrations of this protein might therefore be of relevance.

 
  • References

  • 1 Blankenberg S, McQueen MJ, Smieja M. et al. Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 2006; 114: 201-208.
  • 2 Danesh J, Lewington S, Thompson SG. et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. J Am Med Assoc 2005; 294: 1799-1809.
  • 3 Smith A, Patterson C, Yarnell J. et al. Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study. Circulation 2005; 112: 3080-3087.
  • 4 Tzoulaki I, Murray GD, Lee AJ. et al. Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study. Eur Heart J 2007; 28: 354-362.
  • 5 Aono Y, Ohkubo T, Kikuya M. et al. Plasma Fibrinogen, Ambulatory Blood Pressure, and Silent Cerebrovascular Lesions. The Ohasama Study. Arterioscler Thromb Vasc Biol 2007; 1: 1.
  • 6 Corrado E, Rizzo M, Tantillo R. et al. Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study. Stroke 2006; 37: 482-486.
  • 7 Rothwell PM, Howard SC, Power DA. et al. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke. Stroke 2004; 35: 2300-2305.
  • 8 Di Napoli M, Papa F. Should neurologists measure fibrinogen concentrations?. J Neurol Sci 2006; 246: 5-9.
  • 9 Vibo R, Kõrv J, Roose M. et al. Acute phase proteins and oxidised low-density lipoprotein in association with ischemic stroke subtype, severity and outcome. Free Radic Res 2007; 41: 282-287.
  • 10 Woodward M, Lowe GD, Campbell DJ. et al. Associations of inflammatory and hemostatic variables with the risk of recurrent stroke. Stroke 2005; 36: 2143-2147.
  • 11 Turaj W, Slowik A, Dziedzic T. et al. Increased plasma fibrinogen predicts one–year mortality in patients with acute ischemic stroke. J Neurol Sci 2006; 246: 13-19.
  • 12 Hennerici MG, Kay R, Bogousslavsky J. et al. Intravenous ancrod for acute ischaemic stroke in the European Stroke Treatment with Ancrod Trial: a randomised controlled trial. Lancet 2006; 368: 1871-1878.
  • 13 Sherman DG, Atkinson RP, Chippendale T. et al. Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. Jama 2000; 283: 2395-2403.
  • 14 Tanne D, Macko RF, Lin Y. et al. Hemostatic activation and outcome after recombinant tissue plasminogen activator therapy for acute ischemic stroke. Stroke 2006; 37: 1798-1804.
  • 15 Gonzalez-Conejero R, Fernandez-Cadenas I, Iniesta JA. et al. Role of fibrinogen levels and factor XIII V34L polymorphism in thrombolytic therapy in stroke patients. Stroke 2006; 37: 2288-2293.
  • 16 Brott T, Adams HP Jr., Olinger CP. et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989; 20: 864-870.
  • 17 van Swieten JC, Koudstaal PJ, Visser MC. et al. Interobserver agreement for the assessment of handicap in stroke patients. Stroke 1988; 19: 604-607.
  • 18 Ben Assayag E, Bova I, Berliner S. et al. Gender differences in the expression of erythrocyte aggregation in relation to B beta-fibrinogen gene polymorphisms in apparently healthy individuals. Thromb Haemost 2006; 95: 428-433.
  • 19 Anonymous.. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 2001; 285: 2486-2497.
  • 20 Clauss A. [Rapid physiological coagulation method in determination of fibrinogen]. Acta Haematol 1957; 17: 237-246.
  • 21 International Committee for Standardization in Haematology.. Recommendation of measurement of erythrocyte sedimentation rate of human blood. Am J Clin Pathol 1977; 68: 505-507.
  • 22 Rifai N, Tracy RP, Ridker PM. Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem 1999; 45: 2136-2141.
  • 23 Maresca G, Di Blasio A, Marchioli R. et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999; 19: 1368-1377.
  • 24 Woodward M, Lowe GD, Rumley A. et al. Fibrinogen as a risk factor for coronary heart disease and mortality in middle-aged men and women. The Scottish Heart Health Study. Eur Heart J 1998; 19: 55-62.
  • 25 Danesh J, Collins R, Appleby P. et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. J Am Med Assoc 1998; 279: 1477-1482.
  • 26 Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 448-454.
  • 27 Arntz HR, Perchalla G, Roll D. et al. Blood rheology in acute myocardial infarction: effects of high-dose i.v. streptokinase compared to placebo. Eur Heart J 1992; 13: 275-280.
  • 28 Andrews RK, Berndt MC. Platelet physiology and thrombosis. Thromb Res 2004; 114: 447-453.
  • 29 Schechner V, Shapira I, Berliner S. et al. Significant dominance of fibrinogen over immunoglobulins, C-reactive protein, cholesterol and triglycerides in maintaining increased red blood cell adhesiveness/aggregation in the peripheral venous blood: a model in hypercholesterolaemic patients. Eur J Clin Invest 2003; 33: 955-961.
  • 30 Rugeri L, Levrat A, David JS. et al. Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography. J Thromb Haemost 2007; 5: 289-295.
  • 31 Mahmud E, Cavendish JJ, Tsimikas S. et al. Elevated plasma fibrinogen level predicts suboptimal response to therapy with both single- and double-bolus eptifibatide during percutaneous coronary intervention. J Am Coll Cardiol 2007; 49: 2163-2171.
  • 32 Xu G, Liu X, Zhu W. et al. Feasibility of treating hyperfibrinogenemia with intermittently administered batroxobin in patients with ischemic stroke/transient ischemic attack for secondary prevention. Blood Coagul Fibrinolysis 2007; 18: 193-197.