PDF herunterladen
Semin Thromb Hemost 2010; 36(1): 034-040
DOI: 10.1055/s-0030-1248722
© Thieme Medical Publishers

Disorders of Hemostasis Associated with Chronic Kidney Disease

Diana I. Jalal1 , Michel Chonchol1 , Giovanni Targher2
  • 1Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado
  • 2Section of Endocrinology, Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
13. April 2010 (online)

    Lizenzen und Reprints

ABSTRACT

Chronic kidney disease (CKD) is a growing global health problem. CKD is typically associated with a prothrombotic tendency in the early stages of the disease, whereas in its more advanced stage, that is, end-stage renal disease, patients suffer from a prothrombotic tendency and, in many cases, a bleeding diathesis. The exact etiology behind the coexistence of these conflicting hemostatic disorders is poorly understood. This review critically appraises studies examining the abnormalities in the hemostasis pathway in patients with CKD, as well as the therapeutic options that are currently available to treat these individuals.

KEYWORDS

Chronic kidney disease - thrombosis - bleeding - hemostatic disorders

REFERENCES

  • 1 Furie B, Furie B C. Mechanisms of thrombus formation.  N Engl J Med. 2008;  359(9) 938-949
    CrossrefPubMedSuche in Google Scholar
  • 2 Lane D A, Philippou H, Huntington J A. Directing thrombin.  Blood. 2005;  106(8) 2605-2612
    CrossrefPubMedSuche in Google Scholar
  • 3 Boccardo P, Remuzzi G, Galbusera M. Platelet dysfunction in renal failure.  Semin Thromb Hemost. 2004;  30(5) 579-589
    Thieme ConnectPubMedSuche in Google Scholar
  • 4 Watson S, Berlanga O, Best D, Frampton J. Update on collagen receptor interactions in platelets: is the two-state model still valid?.  Platelets. 2000;  11(5) 252-258
    CrossrefPubMedSuche in Google Scholar
  • 5 Holtkötter O, Nieswandt B, Smyth N et al.. Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen.  J Biol Chem. 2002;  277(13) 10789-10794
    CrossrefPubMedSuche in Google Scholar
  • 6 Bhagwat S S, Hamann P R, Still W C, Bunting S, Fitzpatrick F A. Synthesis and structure of the platelet aggregation factor thromboxane A2.  Nature. 1985;  315(6019) 511-513
    CrossrefPubMedSuche in Google Scholar
  • 7 Savage B, Shattil S J, Ruggeri Z M. Modulation of platelet function through adhesion receptors. A dual role for glycoprotein IIb-IIIa (integrin alpha IIb beta 3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor.  J Biol Chem. 1992;  267(16) 11300-11306
    PubMedSuche in Google Scholar
  • 8 Raines E W. PDGF and cardiovascular disease.  Cytokine Growth Factor Rev. 2004;  15(4) 237-254
    CrossrefPubMedSuche in Google Scholar
  • 9 Perry D J. Antithrombin and its inherited deficiencies.  Blood Rev. 1994;  8(1) 37-55
    CrossrefPubMedSuche in Google Scholar
  • 10 Fulcher C A, Gardiner J E, Griffin J H, Zimmerman T S. Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V.  Blood. 1984;  63(2) 486-489
    PubMedSuche in Google Scholar
  • 11 Grosser T, Fries S, FitzGerald G A. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities.  J Clin Invest. 2006;  116(1) 4-15
    CrossrefPubMedSuche in Google Scholar
  • 12 Moncada S, Higgs A. The L-arginine-nitric oxide pathway.  N Engl J Med. 1993;  329(27) 2002-2012
    CrossrefPubMedSuche in Google Scholar
  • 13 Kolev K, Machovich R. Molecular and cellular modulation of fibrinolysis.  Thromb Haemost. 2003;  89(4) 610-621
    PubMedSuche in Google Scholar
  • 14 Levey A S, Atkins R, Coresh J et al.. Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from Kidney Disease Improving Global Outcomes.  Kidney Int. 2007;  72(3) 247-259
    CrossrefPubMedSuche in Google Scholar
  • 15 Whaley-Connell A T, Sowers J R, Stevens L A Kidney Early Evaluation Program Investigators et al. CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004.  Am J Kidney Dis. 2008;  51(4, suppl 2) S13-S20
    CrossrefPubMedSuche in Google Scholar
  • 16 Thijs A, Nanayakkara P W, Ter Wee P M, Huijgens P C, van Guldener C, Stehouwer C D. Mild-to-moderate renal impairment is associated with platelet activation: a cross-sectional study.  Clin Nephrol. 2008;  70(4) 325-331
    PubMedSuche in Google Scholar
  • 17 Hrafnkelsdóttir T, Ottosson P, Gudnason T, Samuelsson O, Jern S. Impaired endothelial release of tissue-type plasminogen activator in patients with chronic kidney disease and hypertension.  Hypertension. 2004;  44(3) 300-304
    CrossrefPubMedSuche in Google Scholar
  • 18 Cantin B, Després J P, Lamarche B et al.. Association of fibrinogen and lipoprotein(a) as a coronary heart disease risk factor in men (The Quebec Cardiovascular Study).  Am J Cardiol. 2002;  89(6) 662-666
    CrossrefPubMedSuche in Google Scholar
  • 19 Stec J J, Silbershatz H, Tofler G H et al.. Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population.  Circulation. 2000;  102(14) 1634-1638
    CrossrefPubMedSuche in Google Scholar
  • 20 de la Serna G. Fibrinogen: a new major risk factor for cardiovascular disease. A review of the literature.  J Fam Pract. 1994;  39(5) 468-477
    PubMedSuche in Google Scholar
  • 21 Shlipak M G, Fried L F, Crump C et al.. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.  Circulation. 2003;  107(1) 87-92
    CrossrefPubMedSuche in Google Scholar
  • 22 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(1) 133-139
    CrossrefPubMedSuche in Google Scholar
  • 23 Pawlak K, Tankiewicz J, Mysliwiec M, Pawlak D. Tissue factor/its pathway inhibitor system and kynurenines in chronic kidney disease patients on conservative treatment.  Blood Coagul Fibrinolysis. 2009;  , June 1 (Epub ahead of print)
    PubMedSuche in Google Scholar
  • 24 Cetin O, Bekpinar S, Unlucerci Y, Turkmen A, Bayram C, Ulutin T. Hyperhomocysteinemia in chronic renal failure patients: relation to tissue factor and platelet aggregation.  Clin Nephrol. 2006;  65(2) 97-102
    PubMedSuche in Google Scholar
  • 25 Chu A J. Tissue factor mediates inflammation.  Arch Biochem Biophys. 2005;  440(2) 123-132
    CrossrefPubMedSuche in Google Scholar
  • 26 Tay K H, Lip G Y. What “drives” the link between the renin-angiotensin-aldosterone system and the prothrombotic state in hypertension?.  Am J Hypertens. 2008;  21(12) 1278-1279
    CrossrefPubMedSuche in Google Scholar
  • 27 Lindholm L H, Ibsen H, Dahlöf B LIFE Study Group et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.  Lancet. 2002;  359(9311) 1004-1010
    CrossrefPubMedSuche in Google Scholar
  • 28 Lewis E J, Hunsicker L G, Bain R P, Rohde R D. The Collaborative Study Group . The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.  N Engl J Med. 1993;  329(20) 1456-1462
    CrossrefPubMedSuche in Google Scholar
  • 29 Brenner B M, Cooper M E, de Zeeuw D RENAAL Study Investigators et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.  N Engl J Med. 2001;  345(12) 861-869
    CrossrefPubMedSuche in Google Scholar
  • 30 Sechi L A, Novello M, Colussi G et al.. Relationship of plasma renin with a prothrombotic state in hypertension: relevance for organ damage.  Am J Hypertens. 2008;  21(12) 1347-1353
    CrossrefPubMedSuche in Google Scholar
  • 31 Astrup A S, Tarnow L, Pietraszek L et al.. Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate.  Diabetes Care. 2008;  31(6) 1170-1176
    CrossrefPubMedSuche in Google Scholar
  • 32 Huang Y, Noble N A. PAI-1 as a target in kidney disease.  Curr Drug Targets. 2007;  8(9) 1007-1015
    CrossrefPubMedSuche in Google Scholar
  • 33 Segarra A, Chacón P, Martinez-Eyarre C et al.. Circulating levels of plasminogen activator inhibitor type-1, tissue plasminogen activator, and thrombomodulin in hemodialysis patients: biochemical correlations and role as independent predictors of coronary artery stenosis.  J Am Soc Nephrol. 2001;  12(6) 1255-1263
    PubMedSuche in Google Scholar
  • 34 Małyszko J, Małyszko J S, Myśliwiec M. Endothelial cell injury markers in chronic renal failure on conservative treatment and continuous ambulatory peritoneal dialysis.  Kidney Blood Press Res. 2004;  27(2) 71-77
    CrossrefPubMedSuche in Google Scholar
  • 35 Matsuo T, Koide M, Kario K, Suzuki S, Matsuo M. Extrinsic coagulation factors and tissue factor pathway inhibitor in end-stage chronic renal failure.  Haemostasis. 1997;  27(4) 163-167
    PubMedSuche in Google Scholar
  • 36 Takagi M, Wada H, Mukai K et al.. Increased activated protein C: protein C inhibitor complex and decreased protein C inhibitor levels in patients with chronic renal failure on maintenance hemodialysis.  Clin Appl Thromb Hemost. 1999;  5(2) 113-116
    CrossrefPubMedSuche in Google Scholar
  • 37 Tomura S, Nakamura Y, Deguchi F, Ando R, Chida Y, Marumo F. Coagulation and fibrinolysis in patients with chronic renal failure undergoing conservative treatment.  Thromb Res. 1991;  64(1) 81-90
    CrossrefPubMedSuche in Google Scholar
  • 38 Gawaz M P, Dobos G, Späth M, Schollmeyer P, Gurland H J, Mujais S K. Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.  J Am Soc Nephrol. 1994;  5(1) 36-46
    PubMedSuche in Google Scholar
  • 39 Pawlak D, Malyszko J, Malyszko J S, Pawlak K, Buczko W, Mysliwiec M. Peripheral serotonergic system in uremia.  Thromb Res. 1996;  83(2) 189-194
    CrossrefPubMedSuche in Google Scholar
  • 40 Di Minno G, Cerbone A, Usberti M et al.. Platelet dysfunction in uremia. II. Correction by arachidonic acid of the impaired exposure of fibrinogen receptors by adenosine diphosphate or collagen.  J Lab Clin Med. 1986;  108(3) 246-252
    PubMedSuche in Google Scholar
  • 41 Noris M, Benigni A, Boccardo P et al.. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension.  Kidney Int. 1993;  44(2) 445-450
    CrossrefPubMedSuche in Google Scholar
  • 42 Hedges S J, Dehoney S B, Hooper J S, Amanzadeh J, Busti A J. Evidence-based treatment recommendations for uremic bleeding.  Nat Clin Pract Nephrol. 2007;  3(3) 138-153
    CrossrefPubMedSuche in Google Scholar
  • 43 Sabovic M, Salobir B, Preloznik Zupan I, Bratina P, Bojec V, Buturovic Ponikvar J. The influence of the haemodialysis procedure on platelets, coagulation and fibrinolysis.  Pathophysiol Haemost Thromb. 2005;  34(6) 274-278
    CrossrefPubMedSuche in Google Scholar
  • 44 Wasse H, Gillen D L, Ball A M et al.. Risk factors for upper gastrointestinal bleeding among end-stage renal disease patients.  Kidney Int. 2003;  64(4) 1455-1461
    CrossrefPubMedSuche in Google Scholar
  • 45 Kawamura M, Fijimoto S, Hisanaga S, Yamamoto Y, Eto T. Incidence, outcome, and risk factors of cerebrovascular events in patients undergoing maintenance hemodialysis.  Am J Kidney Dis. 1998;  31(6) 991-996
    CrossrefPubMedSuche in Google Scholar
  • 46 Zupan I P, Sabovic M, Salobir B, Ponikvar J B, Cernelc P. Utility of in vitro closure time test for evaluating platelet-related primary hemostasis in dialysis patients.  Am J Kidney Dis. 2003;  42(4) 746-751
    CrossrefPubMedSuche in Google Scholar
  • 47 Kidney Disease Outcomes Quality Initiative .NKF-KDOQI guidelines. http://Available at: www.kidney.org/professionals/kdoqi/guidelines.cfm Accessed January 18, 2010
    PubMedSuche in Google Scholar
  • 48 Charytan D, Kuntz R E. The exclusion of patients with chronic kidney disease from clinical trials in coronary artery disease.  Kidney Int. 2006;  70(11) 2021-2030
    PubMedSuche in Google Scholar
  • 49 Holden R M, Harman G J, Wang M, Holland D, Day A G. Major bleeding in hemodialysis patients.  Clin J Am Soc Nephrol. 2008;  3(1) 105-110
    CrossrefPubMedSuche in Google Scholar
  • 50 Ludwig S, Dharmalingam S, Erickson-Nesmith S et al.. Impact of simvastatin on hemostatic and fibrinolytic regulators in type 2 diabetes mellitus.  Diabetes Res Clin Pract. 2005;  70(2) 110-118
    CrossrefPubMedSuche in Google Scholar
  • 51 Fellström B C, Jardine A G, Schmieder R E AURORA Study Group et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.  N Engl J Med. 2009;  360(14) 1395-1407
    CrossrefPubMedSuche in Google Scholar
  • 52 Viganò G, Benigni A, Mendogni D, Mingardi G, Mecca G, Remuzzi G. Recombinant human erythropoietin to correct uremic bleeding.  Am J Kidney Dis. 1991;  18(1) 44-49
    CrossrefPubMedSuche in Google Scholar
  • 53 Mannucci P M, Remuzzi G, Pusineri F et al.. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia.  N Engl J Med. 1983;  308(1) 8-12
    CrossrefPubMedSuche in Google Scholar
  • 54 Livio M, Mannucci P M, Viganò G et al.. Conjugated estrogens for the management of bleeding associated with renal failure.  N Engl J Med. 1986;  315(12) 731-735
    CrossrefPubMedSuche in Google Scholar

Michel ChoncholM.D. 

Division of Renal Diseases and Hypertension, University of Colorado Denver Health Science Center

4545 E. 9th Avenue Suite 160, Denver, CO 80262

eMail: Michel.Chonchol@ucdenver.edu