Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Platelet dysfunction in uremia

INTRODUCTION

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 multifactorial and includes defects intrinsic to the platelet as well as abnormal platelet-endothelial interaction. Uremic toxins and anemia also play a role.

This topic reviews platelet dysfunction in uremia. Platelet dysfunction in the general population is discussed elsewhere. (See "Congenital and acquired disorders of platelet function".)

CLINICAL AND LABORATORY MANIFESTATIONS

Clinical bleeding in uremia may involve the skin, resulting in easy bruising, or 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).

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2014. | This topic last updated: Jun 26, 2013.
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 ©2014 UpToDate, Inc.
References
Top
  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. 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.
  14. Weigert AL, Schafer AI. Uremic bleeding: pathogenesis and therapy. Am J Med Sci 1998; 316:94.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Linthorst GE, Avis HJ, Levi M. Uremic thrombocytopathy is not about urea. J Am Soc Nephrol 2010; 21:753.
  21. Noris M, Remuzzi G. Uremic bleeding: closing the circle after 30 years of controversies? Blood 1999; 94:2569.
  22. 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.
  23. 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.
  24. Stewart JH, Castaldi PA. Uraemic bleeding: a reversible platelet defect corrected by dialysis. Q J Med 1967; 36:409.
  25. 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.
  26. Lindsay RM, Friesen M, Aronstam A, et al. Improvement of platelet function by increased frequency of hemodialysis. Clin Nephrol 1978; 10:67.
  27. 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.
  28. Mannucci PM. Hemostatic drugs. N Engl J Med 1998; 339:245.
  29. 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.
  30. 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.
  31. 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.
  32. Cases A, Escolar G, Reverter JC, et al. Recombinant human erythropoietin treatment improves platelet function in uremic patients. Kidney Int 1992; 42:668.
  33. Livio M, Gotti E, Marchesi D, et al. Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet 1982; 2:1013.
  34. Hedges SJ, Dehoney SB, Hooper JS, et al. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol 2007; 3:138.
  35. 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.
  36. Zhou XJ, Vaziri ND. Defective calcium signalling in uraemic platelets and its amelioration with long-term erythropoietin therapy. Nephrol Dial Transplant 2002; 17:992.
  37. van Geet C, Hauglustaine D, Verresen L, et al. Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients. Thromb Haemost 1989; 61:117.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. Janson PA, Jubelirer SJ, Weinstein MJ, Deykin D. Treatment of the bleeding tendency in uremia with cryoprecipitate. N Engl J Med 1980; 303:1318.