Thromb Haemost 2005; 93(02): 375-379
DOI: 10.1160/TH04-08-0529
New Technologies and Diagnostic Tools
Schattauer GmbH

The study of anaemia-related haemostasis impairment in haemodialysis patients by in vitro closure time test

Irena Preloznik Zupan
1   Department for Haematology Dialysis, Internal Clinic, University Medical Centre, Ljubljana, Slovenia
,
Miso Sabovic
2   Department for Vascular Diseases, and Dialysis, Internal Clinic, University Medical Centre, Ljubljana, Slovenia
,
Barbara Salobir
2   Department for Vascular Diseases, and Dialysis, Internal Clinic, University Medical Centre, Ljubljana, Slovenia
,
Jadranka Buturovic Ponikvar
3   Nephrology and Dialysis, Internal Clinic, University Medical Centre, Ljubljana, Slovenia
,
Peter Cernelc
1   Department for Haematology Dialysis, Internal Clinic, University Medical Centre, Ljubljana, Slovenia
,
Janez Lavre
4   Department for Nephrology and Dialysis, Slovenj Gradec General Hospital, Slovenia
,
Bojan Vujkovac
4   Department for Nephrology and Dialysis, Slovenj Gradec General Hospital, Slovenia
› Author Affiliations
Further Information

Publication History

Received 20 August 2004

Accepted after resubmission 25 January 2004

Publication Date:
11 December 2017 (online)

Summary

It is known that anaemia in haemodialysis patients could contribute to haemostasis impairment. However, the precise relation between the degree of anaemia and the degree of haemostasis impairment is not known, nor the optimal level of hematocrit above which anaemia no longer disturbs haemostasis. Our study addresses these clinically relevant questions by employing in vitro closure time test, a new method in which the process of platelet adhesion and aggregation following vascular injury is simulated in vitro in samples of whole blood. We studied 63 haemodialysis patients, with 30 age-matched, healthy controls. Results show that patients with hematocrit below 0.32 (N=28) had significantly impaired primary haemostasis, in contrast to patients with hematocrit above 0.32 (N=35), as measured by both types of closure time test. A significant negative association was found between hematocrit values and closure time (CEPI cartridges: rho=–0.41, p <0.001; CADP cartridges: rho =–0.47, p <0.001). A multiple logistic regression model for predicting prolonged closure time confirmed this finding. Nonparametric curve fitting enabled estimation of the level of hematocrit at which the values of in vitro closure time in haemodialysis patients do not differ from those in the controls at approximately 0.35. ROC analysis confirmed this to be the optimal threshold for predicting prolonged closure time for both cartridges. By using in vitro closure time test, we confirmed that anaemia correlates with the severity of haemostasis impairment. We estimated the target level of hematocrit above which anaemia no longer affects haemostasis to be about 0.35.These new results (and new assay) appear to have clinical value for treating haemodialysis patients.

 
  • References

  • 1 Livio M, Marchesi D, Remuzzi G. Coagulation abnormalities in uremia.. Semin Nephrol 1985; 5: 82-90.
  • 2 Remuzzi G. Bleeding in renal failure.. Lancet 1988; 1: 1205-8.
  • 3 Eberst ME, Berkowitz LR. Haemostasis in renal disease: Pathophysiology and management.. Am J Med 1994; 96: 168-79.
  • 4 Rabelink TJ, Zwaginga JJ, Koomans HA. et al Thrombosis and haemostasis in renal disease.. Kidney Int 1994; 46: 287-96.
  • 5 Mezzano D, Tagle R, Panes O. et al Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis.. Thromb Haemost 1996; 76: 312-21.
  • 6 Turrito VT, Baumgartner HR. Platelet interaction with subendothelium in a perfusion system: Physical role of red blood cell.. Microvasc Res 1975; 9: 335-44.
  • 7 Turrito VT, Weiss HJ. Red blood cells: their dual role in thrombus formation.. Science 1980; 207: 541-3.
  • 8 Livio M, Gotti E, Marchesi D. et al Uremic bleeding: role of anaemia and beneficial effect of red cell transfusions.. Lancet 1982; 2: 1013-5.
  • 9 Fernandez F, Goudable C, Sie P. et al Low hematocrit and prolonged bleeding time in uraemic patients: Effect of red cell transfusions.. Br J Haematol 1985; 59: 139-48.
  • 10 Moia M, Mannucci PM, Vizzotto L. et al Improvement in the hemostatic defect of uraemia after treatment with recombinant human erythropoietin.. Lancet 1987; 2: 1227-9.
  • 11 Escolar G, Cases A, Vinas M. et al Evaluation of acquired platelet dysfunctions in uremic and cirrotic patients using the platelet function analyzer (PFA- 100TM): influence of hematocrit elevation.. Haematologica 1999; 84: 614-9.
  • 12 Zupan IP, Åabovic M, Salobir B. et al Utility of in vitro closure time test for evaluating platelet-related primary haemostasis in dialysis patients.. Am J Kidney Dis 2003; 42: 746-51.
  • 13 Drueke TB, Eckardt KU, Frei U. et al Does early anaemia correction prevent complication of chronic renal failure?. Clin Nephrol 1999; 51: 1-11.
  • 14 Favaloro EJ. Clinical application of the PFA-100.. Curr Opin Hematol 2002; 9: 407-15.
  • 15 Ortel TL, James AH, Thames EH. et al Assessment of primary haemostasis by PFA-100 analysis in a tertiary care center.. Thromb Haemost 2000; 84: 93-7.
  • 16 Koscielny J, von Tempelhoff GF, Ziemer S. et al A practical concept for preoperative identification of patients with impaired primary haemostasis.. Clin Appl Thromb Hemost 2004; 10: 195-204.
  • 17 Koscielny J, von Tempelhoff GF, Ziemer S. et al A practical concept for preoperative management of patients with impaired primary haemostasis.. Clin Appl Thromb Hemost 2004; 10: 155-66.
  • 18 Anand A, Feffer SE. Hematocrit and bleeding time: an update.. South Med J 1994; 87: 299-301.
  • 19 Akizawa T, Kinugasa E, Kitaoka T. et al Effects of recombinant human erythropoietin and correction anaemia on platelet function in haemodialysis patients.. Nephron 1991; 58: 400-6.
  • 20 Kundu SK, Heilmann EJ, Sio R. et al Description of an in vitro platelet function analyzer PFA-100.. Semin Thromb Hemost 1995; 21 (Suppl. 02) 106-12.
  • 21 Mammen EF, Comp PC, Gosselin R. et al PFA- 100TM System: a new method for assessment of platelet dysfunction.. Semin Thromb Hemost 1998; 24: 195-202.
  • 22 Favaloro EJ. Utility of the PFA-100 for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations.. Haemophilia 2001; 7: 170-9.
  • 23 Avram MM, Blaustein D, Fein PA. et al Hemoglobin predicts long-term survival in dialysis patients: a 15-year single-center longitudinal study and a correlation trend between prealbumin and hemoglobin.. Kidney Int 2003; (Suppl) 87: S6-S11.