Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Platelet dysfunction in uremia

Jeffrey S Berns, MD
Steven Coutre, MD
Section Editor
Thomas A Golper, MD
Deputy Editor
Alice M Sheridan, MD


The association between renal dysfunction and bleeding was recognized more than 200 years ago [1]. However, there remains an incomplete understanding of the underlying pathophysiology. Impaired platelet function is one of the main determinants of uremic bleeding. This impairment is due largely to incompletely defined inhibitors of platelet function in the plasma of patients with markedly reduced kidney function. Abnormal platelet-endothelial interaction and anemia also play a role.

This topic reviews platelet dysfunction in uremia. It should be noted that the term "uremic" is generally not specifically defined in most studies of this topic review, which typically include patients undergoing regular maintenance dialysis treatments and well as those with chronic kidney disease (CKD) who are not on dialysis. Most of these patients are not overtly "uremic." Platelet dysfunction in other settings is discussed elsewhere. (See "Congenital and acquired disorders of platelet function".)


Clinical bleeding in uremia may involve the skin, resulting in easy bruising; the oral and nasal mucosa; gingiva; gastrointestinal and urinary tracts; and respiratory system. Excessive bleeding may also occur in response to injury or invasive procedures [2-4].

Uremic patients may display increased bleeding sensitivity to aspirin as there is a transient, cyclooxygenase-independent prolongation of the bleeding time following the use of aspirin in uremic patients that is greater than that seen in normal subjects taking aspirin [5].

Although an association between bleeding time prolongation and uremia has long been suggested [6], there are no good studies that unequivocally demonstrate an increased risk of either spontaneous bleeding or bleeding with a procedure that is associated with a prolonged bleeding time among patients with chronic kidney disease (CKD). The bleeding time is rarely done any longer due to poor standardization, accuracy, reproducibility, and ability to predict bleeding risk.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 18, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Morgagni GB. Opera Omnia. Ex Typographia Remondiniana. Venezia, Italy, 1764.
  2. RATH CE, MAILLIARD JA, SCHREINER GE. Bleeding tendency in uremia. N Engl J Med 1957; 257:808.
  3. FERGUSON JH, LEWIS JH, ZUCKER MB. Bleeding tendency in uremia. Blood 1956; 11:1073.
  4. Molino D, De Lucia D, Gaspare De Santo N. Coagulation disorders in uremia. Semin Nephrol 2006; 26:46.
  5. Gaspari F, Viganò G, Orisio S, et al. Aspirin prolongs bleeding time in uremia by a mechanism distinct from platelet cyclooxygenase inhibition. J Clin Invest 1987; 79:1788.
  6. Steiner RW, Coggins C, Carvalho AC. Bleeding time in uremia: a useful test to assess clinical bleeding. Am J Hematol 1979; 7:107.
  7. Galbusera M, Remuzzi G, Boccardo P. Treatment of bleeding in dialysis patients. Semin Dial 2009; 22:279.
  8. Eknoyan G, Wacksman SJ, Glueck HI, Will JJ. Platelet function in renal failure. N Engl J Med 1969; 280:677.
  9. Maejima M, Takahashi S, Hatano M. [Platelet aggregation in chronic renal failure--whole blood aggregation and effect of guanidino compounds]. Nihon Jinzo Gakkai Shi 1991; 33:201.
  10. Escolar G, Díaz-Ricart M, Cases A. Uremic platelet dysfunction: past and present. Curr Hematol Rep 2005; 4:359.
  11. Lee HK, Kim YJ, Jeong JU, et al. Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients. Nephron Clin Pract 2010; 114:c248.
  12. Waki K, Hayashi A, Ikeda S, et al. Measuring platelet aggregation in dialysis patients with a whole blood aggregometer by the screen filtration pressure method. Ther Apher Dial 2011; 15:203.
  13. Zeck J, Schallheim J, Lew SQ, DePalma L. Whole blood platelet aggregation and release reaction testing in uremic patients. Biomed Res Int 2013; 2013:486290.
  14. Marques M, Sacristán D, Mateos-Cáceres PJ, et al. Different protein expression in normal and dysfunctional platelets from uremic patients. J Nephrol 2010; 23:90.
  15. Weigert AL, Schafer AI. Uremic bleeding: pathogenesis and therapy. Am J Med Sci 1998; 316:94.
  16. Koo JY, Kadonaga JN, Wintroub BV, Lozada-Nur FI. The development of B-cell lymphoma in a patient with psoriasis treated with cyclosporine. J Am Acad Dermatol 1992; 26:836.
  17. Escolar G, Cases A, Bastida E, et al. Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. Blood 1990; 76:1336.
  18. Gawaz MP, Dobos G, Späth M, et al. Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease. J Am Soc Nephrol 1994; 5:36.
  19. Benigni A, Boccardo P, Galbusera M, et al. Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients with uremia. Am J Kidney Dis 1993; 22:668.
  20. Warrell RP Jr, Hultin MB, Coller BS. Increased factor VIII/von Willebrand factor antigen and von Willebrand factor activity in renal failure. Am J Med 1979; 66:226.
  21. Di Minno G, Martinez J, McKean ML, et al. Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis. Am J Med 1985; 79:552.
  22. Sreedhara R, Itagaki I, Lynn B, Hakim RM. Defective platelet aggregation in uremia is transiently worsened by hemodialysis. Am J Kidney Dis 1995; 25:555.
  23. Linthorst GE, Avis HJ, Levi M. Uremic thrombocytopathy is not about urea. J Am Soc Nephrol 2010; 21:753.
  24. Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood 1999; 94:2569.
  25. Hedges SJ, Dehoney SB, Hooper JS, et al. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol 2007; 3:138.
  26. Martin W, Villani GM, Jothianandan D, Furchgott RF. Blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation of rabbit aorta by certain ferrous hemoproteins. J Pharmacol Exp Ther 1985; 233:679.
  27. Remuzzi G, Perico N, Zoja C, et al. Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin Invest 1990; 86:1768.
  28. Noris M, Benigni A, Boccardo P, et al. Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and dialysis hypotension. Kidney Int 1993; 44:445.
  29. Stewart JH, Castaldi PA. Uraemic bleeding: a reversible platelet defect corrected by dialysis. Q J Med 1967; 36:409.
  30. Nenci GG, Berrettini M, Agnelli G, et al. Effect of peritoneal dialysis, haemodialysis and kidney transplantation on blood platelet function. I. Platelet aggregation by ADP and epinephrine. Nephron 1979; 23:287.
  31. Lindsay RM, Friesen M, Aronstam A, et al. Improvement of platelet function by increased frequency of hemodialysis. Clin Nephrol 1978; 10:67.
  32. Mannucci PM, Remuzzi G, Pusineri F, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 1983; 308:8.
  33. Mannucci PM. Hemostatic drugs. N Engl J Med 1998; 339:245.
  34. Sidawy AN, Spergel LM, Besarab A, et al. The Society for Vascular Surgery: clinical practice guidelines for the surgical placement and maintenance of arteriovenous hemodialysis access. J Vasc Surg 2008; 48:2S.
  35. Zeigler ZR, Megaludis A, Fraley DS. Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. Am J Hematol 1992; 39:90.
  36. Gordz S, Mrowietz C, Pindur G, et al. Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand's disease. Clin Hemorheol Microcirc 2005; 32:83.
  37. Kim JH, Baek CH, Min JY, et al. Desmopressin improves platelet function in uremic patients taking antiplatelet agents who require emergent invasive procedures. Ann Hematol 2015; 94:1457.
  38. Byrnes JJ, Larcada A, Moake JL. Thrombosis following desmopressin for uremic bleeding. Am J Hematol 1988; 28:63.
  39. Cases A, Escolar G, Reverter JC, et al. Recombinant human erythropoietin treatment improves platelet function in uremic patients. Kidney Int 1992; 42:668.
  40. Livio M, Gotti E, Marchesi D, et al. Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet 1982; 2:1013.
  41. Diaz-Ricart M, Etebanell E, Cases A, et al. Erythropoietin improves signaling through tyrosine phosphorylation in platelets from uremic patients. Thromb Haemost 1999; 82:1312.
  42. Zhou XJ, Vaziri ND. Defective calcium signalling in uraemic platelets and its amelioration with long-term erythropoietin therapy. Nephrol Dial Transplant 2002; 17:992.
  43. van Geet C, Hauglustaine D, Verresen L, et al. Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients. Thromb Haemost 1989; 61:117.
  44. Livio M, Mannucci PM, Viganò G, et al. Conjugated estrogens for the management of bleeding associated with renal failure. N Engl J Med 1986; 315:731.
  45. Bronner MH, Pate MB, Cunningham JT, Marsh WH. Estrogen-progesterone therapy for bleeding gastrointestinal telangiectasias in chronic renal failure. An uncontrolled trial. Ann Intern Med 1986; 105:371.
  46. Heistinger M, Stockenhuber F, Schneider B, et al. Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF. Kidney Int 1990; 38:1181.
  47. Viganò G, Gaspari F, Locatelli M, et al. Dose-effect and pharmacokinetics of estrogens given to correct bleeding time in uremia. Kidney Int 1988; 34:853.
  48. Sloand JA, Schiff MJ. Beneficial effect of low-dose transdermal estrogen on bleeding time and clinical bleeding in uremia. Am J Kidney Dis 1995; 26:22.
  49. Viganò G, Zoja C, Corna D, et al. 17 beta-estradiol is the most active component of the conjugated estrogen mixture active on uremic bleeding by a receptor mechanism. J Pharmacol Exp Ther 1990; 252:344.
  50. Shemin D, Elnour M, Amarantes B, et al. Oral estrogens decrease bleeding time and improve clinical bleeding in patients with renal failure. Am J Med 1990; 89:436.
  51. Zoja C, Noris M, Corna D, et al. L-arginine, the precursor of nitric oxide, abolishes the effect of estrogens on bleeding time in experimental uremia. Lab Invest 1991; 65:479.
  52. Janson PA, Jubelirer SJ, Weinstein MJ, Deykin D. Treatment of the bleeding tendency in uremia with cryoprecipitate. N Engl J Med 1980; 303:1318.