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Uremic Toxins and Platelet Function

Uremic Toxins and Platelet Function Abstract The hemostatic abnormalities in patients with uremia are related to acquired functional platelet defects. Evidence derived from dialysis, in vitro studies with cell-free uremic plasma, and the ingestion or infusion of uremic metabolities indicate that one or more dialyzable toxins are responsible for altering the function of intrinsically normal platelets. Urea, creatinine, methylguanidine, phenol and phenolic acids, and guanidinosuccinic acid (GSA) have been proposed for this role. These substances affect platelet aggregation, platelet factor 3 activation induced by adenosine diphosphate (ADP), platelet ultrastructure, and bleeding time. Only guanidinosuccinic acid and perhaps the phenolic compounds thus far meet the most rigid criteria for toxins affecting platelet function. A toxin which competitively limits internal platelet transformation in response to exogenous adenosine diphosphate could account for the hemostatic abnormalities found in renal failure. References 1. Salzman EW, Neri LL: Adhesiveness of blood platelets in uremia. Thromb Diath Haemorrh 15:84-92,1966. 2. Castaldi PA, Rozenberg MC, Stewart JH: The bleeding disorder of uraemia: A qualitative platelet defect. Lancet 2:66-69,1966.Crossref 3. Eknoyan G, Wacksman SJ, Glueck HI, et al: Platelet function in renal failure. New Eng J Med 280:677-681,1969.Crossref 4. Horowitz HI, Stein IM, Cohen BD, et al: Further studies on the platelet inhibitory effect of guanidinosuccinic acid and its role in uremic bleeding. Amer J Med , to be published. 5. Rabiner SF, Molinas F: The role of phenol and phemolic acids on the thrombocytopathy and defective platelet aggregation of patients with renal failure. Amer J Med , to be published. 6. Horowitz HI, Cohen BD, Martinez P, et al: Defective ADP-induced platelet factor 3 activation in uremia. Blood 30:331-340,1967. 7. Rabiner SF, Hrodek 0: Platelet factor 3 in normal subjects and patients with renal failure. J Clin Invest 47:901-912, 1968.Crossref 8. Altschuler G, Marcus AJ, Ullman HL: Platelets and platelet phosphatides in uremia. Blood 16:1439-1446,1960. 9. Pitney WR, Hinterberger H, Potter M: Adenine nucleotides in platelets from normal and uraemic subjects: The effect of passage through glass bead filters. Thromb Diath Haemorrh 19:36-40,1968. 10. Hellem AJ, Odegaard AE, Skalhegg BA: Platelet adhesiveness in chronic renal failure , in International Society of Haematology, Abstracts of the 10th Congress . Stockholm, Ljunglofo Litograftsha, 1964, P.K. p 1. 11. Praga C, Cortellaro M: Diminuzione Delladhesivita Piastrinica al vetro in Soggetti Normali Dopo Corico Orale di Creatinina. Read before the First International Symposium on Tissue Factors in the Homeostasis of the Coagulation-Fibrinolysis System, Florence, Italy, 1967. 12. Stewart JJ, Castaldi PA: Uraemic bleeding: A reversible platelet defect corrected by dialysis. Quart J Med 36:409-423, 1967. 13. Somer JB, Stewart JH, Castaldi PA: The effect of urea on the aggregation of normal human platelets. Thromb Diath Haemorrh 19:64-69,1968. 14. Fantl P: The varying influence of urea on blood platelets. Aust J Exp Biol Med 44:451-454, 1966.Crossref 15. Giovannetti S, Biagini M, Cioni L: Evidence that methylguanidine is retained in chronic renal failure. Experientia 24:341-342, 1968.Crossref 16. Zweifler AJ, Sanbar SS: Inhibition of platelet adhesiveness and aggregation by benzyl alcohol and phenol. Thromb Diath Haemorrh 21:362-366, 1969. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Uremic Toxins and Platelet Function

Archives of Internal Medicine , Volume 126 (5) – Nov 1, 1970

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Publisher
American Medical Association
Copyright
Copyright © 1970 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1970.00310110093013
Publisher site
See Article on Publisher Site

Abstract

Abstract The hemostatic abnormalities in patients with uremia are related to acquired functional platelet defects. Evidence derived from dialysis, in vitro studies with cell-free uremic plasma, and the ingestion or infusion of uremic metabolities indicate that one or more dialyzable toxins are responsible for altering the function of intrinsically normal platelets. Urea, creatinine, methylguanidine, phenol and phenolic acids, and guanidinosuccinic acid (GSA) have been proposed for this role. These substances affect platelet aggregation, platelet factor 3 activation induced by adenosine diphosphate (ADP), platelet ultrastructure, and bleeding time. Only guanidinosuccinic acid and perhaps the phenolic compounds thus far meet the most rigid criteria for toxins affecting platelet function. A toxin which competitively limits internal platelet transformation in response to exogenous adenosine diphosphate could account for the hemostatic abnormalities found in renal failure. References 1. Salzman EW, Neri LL: Adhesiveness of blood platelets in uremia. Thromb Diath Haemorrh 15:84-92,1966. 2. Castaldi PA, Rozenberg MC, Stewart JH: The bleeding disorder of uraemia: A qualitative platelet defect. Lancet 2:66-69,1966.Crossref 3. Eknoyan G, Wacksman SJ, Glueck HI, et al: Platelet function in renal failure. New Eng J Med 280:677-681,1969.Crossref 4. Horowitz HI, Stein IM, Cohen BD, et al: Further studies on the platelet inhibitory effect of guanidinosuccinic acid and its role in uremic bleeding. Amer J Med , to be published. 5. Rabiner SF, Molinas F: The role of phenol and phemolic acids on the thrombocytopathy and defective platelet aggregation of patients with renal failure. Amer J Med , to be published. 6. Horowitz HI, Cohen BD, Martinez P, et al: Defective ADP-induced platelet factor 3 activation in uremia. Blood 30:331-340,1967. 7. Rabiner SF, Hrodek 0: Platelet factor 3 in normal subjects and patients with renal failure. J Clin Invest 47:901-912, 1968.Crossref 8. Altschuler G, Marcus AJ, Ullman HL: Platelets and platelet phosphatides in uremia. Blood 16:1439-1446,1960. 9. Pitney WR, Hinterberger H, Potter M: Adenine nucleotides in platelets from normal and uraemic subjects: The effect of passage through glass bead filters. Thromb Diath Haemorrh 19:36-40,1968. 10. Hellem AJ, Odegaard AE, Skalhegg BA: Platelet adhesiveness in chronic renal failure , in International Society of Haematology, Abstracts of the 10th Congress . Stockholm, Ljunglofo Litograftsha, 1964, P.K. p 1. 11. Praga C, Cortellaro M: Diminuzione Delladhesivita Piastrinica al vetro in Soggetti Normali Dopo Corico Orale di Creatinina. Read before the First International Symposium on Tissue Factors in the Homeostasis of the Coagulation-Fibrinolysis System, Florence, Italy, 1967. 12. Stewart JJ, Castaldi PA: Uraemic bleeding: A reversible platelet defect corrected by dialysis. Quart J Med 36:409-423, 1967. 13. Somer JB, Stewart JH, Castaldi PA: The effect of urea on the aggregation of normal human platelets. Thromb Diath Haemorrh 19:64-69,1968. 14. Fantl P: The varying influence of urea on blood platelets. Aust J Exp Biol Med 44:451-454, 1966.Crossref 15. Giovannetti S, Biagini M, Cioni L: Evidence that methylguanidine is retained in chronic renal failure. Experientia 24:341-342, 1968.Crossref 16. Zweifler AJ, Sanbar SS: Inhibition of platelet adhesiveness and aggregation by benzyl alcohol and phenol. Thromb Diath Haemorrh 21:362-366, 1969.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Nov 1, 1970

References

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