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Journal ArticleDOI

Uremic Toxins and Platelet Function

01 Nov 1970-JAMA Internal Medicine (American Medical Association)-Vol. 126, Iss: 5, pp 823-826
TL;DR: A toxin which competitively limits internal platelet transformation in response to exogenous adenosine diphosphate could account for the hemostatic abnormalities found in renal failure.
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.
Citations
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Journal ArticleDOI
TL;DR: A 40-year-old man has undergone chronic hemodialysis for 7 years and had nephrotic syndrome from age 2 to 5 years but was apparently well until age 18, when proteinuria was detected again.

371 citations

Journal Article
TL;DR: A 40-year-old man has undergone chronic hemodialysis for 7 years as discussed by the authors, and he had nephrotic syndrome from age 2 to 5 years but was apparently well until age 18, when proteinuria was detected again.
Abstract: A 40-year-old man has undergone chronic hemodialysis for 7 years. He had nephrotic syndrome from age 2 to 5 years but was apparently well until age 18, when proteinuria was detected again. At age 28, hypertension was noted. Hematocrit was 36%; white blood cell count, 6700/mm3; and creatinine clearance, 69 mI/mm. Chest x-ray and intravenous pyelogram were normal. A renal biopsy disclosed chronic glomerulonephritis. At age 31, a grade lI/VI holosystolic cardiac murmur was noted. Hematocrit was 29%; serum creatinine, 9.8 mg/dl; BUN, 83 mg/dl; phosphate, 5.6 mg/dl; and calcium, 7.2 mg/dl. Calcium carbonate, aluminum hydroxide, dihydrotachysterol, and folic acid were prescribed. At age 32, his blood pressure was 145/90 mm Hg. The hematocrit was 20.5%; serum creatinine, 12.1 mg/dl; and BUN, 87 mg/dl. Fluoxymesterone, 40 mg daily, was prescribed. At age 33, uremic symptoms were evident. The hematocrit was 14%; white blood cell count, 7000/mm3; serum creatinine, 22 mg/dl; BUN, 140 mg/dl; serum bicarbonate, 14 mEq/liter; and serum potassium, 4.3 mEq/Iiter. Serum ferritin was 218 ng/ml. Hepatitis B surface antibody was positive and hepatitis B antigen negative. A plain chest film showed generalized cardiomegaly, and an electrocardiogram revealed anterolateral ischemia. Two units of red blood cells were transfused and hemodialysis was begun. He improved and returned to his home in Alaska to continue chronic hemodialysis. Because his hematocrit fell repeatedly to levels of

318 citations

Journal ArticleDOI
TL;DR: Evidence is provided that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects, which may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes.
Abstract: The coagulation system has gained much interest again as new anticoagulatory substances have been introduced into clinical practice. Especially patients with renal failure are likely candidates for such a therapy as they often experience significant comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal failure on new anticoagulants have experienced excessive bleeding which can be related to a changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even without any interference with coagulation modifying drugs, is already profoundly changed during renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent an important cause for the morbidity and mortality of such patients. The underlying reasons for these coagulation disorders involve the changed interaction of different components of the coagulation system such as the coagulation cascade, the platelets and the vessel wall in the metabolic conditions of renal failure. Recent work provides evidence that new factors such as microparticles (MPs) can influence the coagulation system in patients with renal insufficiency through their potent procoagulatory effects. Interestingly, MPs may also contain microRNAs thus inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the findings on the complex pathophysiology of coagulation disorders including new factors such as MPs and microRNAs in patients with renal insufficiency.

310 citations

Book ChapterDOI
01 Jan 1983
TL;DR: This chapter is organized as shown in Figure 1 and consists of two basic lines of development: consideration of the dialyzer and its operating principles and application of mass balance principles to various solute systems and the effect of Dialyzer use on solute control during intermittent dialysis therapy.
Abstract: Intermittent dialysis therapy is used in chronic uremia to re-establish body water solute concentrations that cannot be achieved by the natural organ. In this sense, the dialyzer becomes an artificial kidney and it is through the transport of substances by this device that chemical and biophysical control consistent with continued survival is achieved. This chapter is organized as shown in Figure 1 and consists of two basic lines of development: 1. Consideration of the dialyzer and its operating principles, 2. Application of mass balance principles to various solute systems and the effect of dialyzer use on solute control during intermittent dialysis therapy.

281 citations

Journal ArticleDOI
15 Oct 1999-Blood
TL;DR: M ORGAGNI in his “Opera Omnia”-Epistola Anatomico-Medica XLI-1764, Sermo est de Urinae Suppressione was the first to recognize the remarkable association between bleeding and renal dysfunction, which became a clinical problem in the early days of dialysis, when patients sometimes died.

185 citations

References
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Journal ArticleDOI
TL;DR: Observations suggest a direct effect of urea or one of its metabolites on platelet function and help define the bleeding defect of uremia.
Abstract: Study of the bleeding tendency in uremia in 26 subjects, 10 of whom were bleeding, showed platelet counts and plasma coagulation factors to be normal. There was a significant inverse correlation between the level of serum urea nitrogen and creatinine, and the adhesiveness of the platelets. Platelet adhesiveness was significantly lower in bleeding subjects than in those without bleeding. A prolonged bleeding time was more frequent in the group with bleeding. Abnormal prothrombin consumption was found only in bleeding subjects despite normal numbers of platelets and plasma coagulation factors. The ingestion of urea in 10 normal volunteers prolonged the bleeding time in five and decreased the platelet adhesiveness, which fell to pathologic levels, in eight. These observations suggest a direct effect of urea or one of its metabolites on platelet function and help define the bleeding defect of uremia.

188 citations

Journal ArticleDOI
TL;DR: GSA levels and the degree of inhibitio of ADP-induced PF-3 activation decreased in parallel in the serum and plasma of uremic patients undergoing peritoneal dialysis, and can account for a number of the in vitro abnormalities of Uremic platelet function and may be partly responsible for the bleeding syndrome of u Remia.

184 citations

Journal ArticleDOI
01 Sep 1967-Blood
TL;DR: A test for platelet thromboplastic function measuring the activation of platelet factor 3 on incubation of ADP with citrated platelet-rich plasma has been standardized in terms ofADP and platelet concentrations, and amount of agitation, to give sensitive and reproducible results.

119 citations