Chronic Renal Failure - Platelet Function

4/22/02 (Patel)

Question: Why is there decreased platelet function in some chronic renal failure patients?

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Unique Identifier:8873344

Authors: Malyszko J. Malyszko JS. Pawlak D. Pawlak K. Buczko W. Mysliwiec M.

Institution: Department of Nephrology, Bialystok Medical School, Poland.

Title: Hemostasis, platelet function and serotonin in acute and chronic renal failure.

Source: Thrombosis Research. 83(5):351-61, 1996 Sep 1.

Abstract: A pathogenetic role for fibrin deposition and platelet activation in the kidney is thought to play a role in the pathogenesis of acute renal failure (ARF). Thus, some fibrinolytic parameters and platelet function have been studied in 17 patients with ARF and compared to healthy volunteers and subjects with chronic renal failure (CRF). Since serotonin may participate in pathological processes resulting from platelet/vessel wall interactions, its level in the whole blood and plasma was also assayed. In ARF and CRF platelet aggregatory responses in both whole blood and in platelet rich plasma upon stimulation with various agonists (collagen, arachidonic acid, ADP, ristocetin) were lower than those obtained in healthy volunteers. Increased levels of lipoprotein (a), von Willebrand factor (vWF) and fibronectin were found in ARF relative to controls. Protein C activity was significantly lower in patients with ARF. Euglobulin clot lysis time was prolonged in ARF and CRF, reflecting a decreased overall fibrinolytic activity. Activity of tissue plasminogen activator (tPA) inhibitor (PAI) and PAI:Ag were higher in ARF, whereas tPA:Ag, urokinase, tPA/PAI complexes, thrombin-antithrombin complexes (TAT), plasmin-antiplasmin (PAP) complexes, fibrinogen, and F1+2 did not differ between ARF and controls. In CRF elevated levels of TAT, PAP, fibrinogen and prothrombin fragments F1+2 were found, whereas concentration of fibronectin was lowered when compared to controls. In both groups of renal failure patients increased levels of fibrin monomers and d-dimer were found relative to healthy volunteers. Whole blood serotonin was significantly lower, whereas plasma serotonin was significantly higher in patients with ARF and CRF relative to controls. Serotonin uptake and its release from platelets were markedly diminished in patients with ARF and CRF. Chronic renal failure exhibit a slightly different pattern of coagulopathies that acute renal failure. CAS Registry/EC Number 0 (Antiplasmin). 0 (Fibronectins). 0 (Lipoprotein(a)). 0 (Peptide Fragments). 0 (Plasminogen Activator Inhibitor 1). 0 (antithrombin III-protease complex). 0 (prothrombin fragment 1.2). 0 (von Willebrand Factor). 1404-55-3 (Ristocetin). 50-67-9 (Serotonin). 506-32-1 (Arachidonic Acid). 58-64-0 (Adenosine Diphosphate). 9000-94-6 (Antithrombin III). 9001-26-7 (Prothrombin). 9007-34-5 (Collagen). EC 3-4 (Peptide Hydrolases). EC 3-4-21-68 (Tissue Plasminogen Activator). EC 3-4-21-7 (Plasmin).

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Unique Identifier:2024233

Authors: Michalak E. Walkowiak B. Paradowski M. Cierniewski CS.

Institution: Department of Nephrology, Medical School, Lodz, Poland.

Title: The decreased circulating platelet mass and its relation to bleeding time in chronic renal failure. [see comments.].

Source: Thrombosis & Haemostasis. 65(1):11-4, 1991 Jan 23.

Abstract: The mean platelet volume, measured optically and by the electrical impedance method, was analysed in the patients with chronic renal failure. All parameters describing the circulating platelet biomass except the platelet volume heterogeneity were decreased in these patients. There is a strong inverse relation between the Ivy bleeding time and the platelet mass in the patient group. Our results indicate that the smaller platelets circulating in the patients with chronic renal failure may contribute to the uremic bleeding diathesis, and disturbed thrombocytopoiesis occurs in chronic renal failure.

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Unique Identifier:2220759

Authors: Soslau G. Brodsky I. Putatunda B. Parker J. Schwartz AB.

Institution: Department of Biological Science, Hahnemann Medical School and Hospital, Philadelphia.

Title: Selective reduction of serotonin storage and ATP release in chronic renal failure patients platelets.

Source: American Journal of Hematology. 35(3):171-8, 1990 Nov.

Abstract: Hemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly (P less than .001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co-stored with ATP, is unaltered. Analysis of the CRF-derived platelets reflects a selective acquired storage pool defect with significantly (P less than .001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different (P less than .02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times (P less than .001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patients. CAS Registry/EC Number 50-67-9 (Serotonin). 56-65-5 (Adenosine Triphosphate). 58-64-0 (Adenosine Diphosphate).

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Unique Identifier:3187950

Authors: Gordge MP. Faint RW. Rylance PB. Neild GH.

Institution: Dept. of Renal Medicine, St. Philips Hospital, London, UK.

Title: Platelet function and the bleeding time in progressive renal failure.

Source: Thrombosis & Haemostasis. 60(1):83-7, 1988 Aug 30.

Abstract: Bleeding time and platelet function tests were performed on 31 patients with progressive chronic renal failure (CRF) due to non-immunological (urological) causes, and compared with 22 healthy controls. Patients were classified as mild (plasma creatinine less than 300 mumol/l), moderate (300-600 mumol/l) or severe renal failure (greater than 600 mumol/l). Bleeding time was rarely prolonged in mild and moderate CRF and mean bleeding time significantly elevated only in severe CRF (p less than 0.005). Haematocrit was the only index which correlated with bleeding time (r = -0.40). Platelet counts, collagen stimulated thromboxane generation, and platelet aggregation responses to ADP, collagen and ristocetin were all either normal or increased in all three CRF groups, but thromboxane production in clotting blood was reduced. Plasma fibrinogen, C reactive protein and von Willebrand factor (vWF) were elevated in proportion to CRF. We found no evidence that defects in platelet aggregation or platelet interaction with vWF prolong the bleeding time in patients with progressive CRF. CAS Registry/EC Number 54397-85-2 (Thromboxane B2).

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Unique Identifier:6216810

Authors: Eknoyan G. Brown CH 3rd.

Title: Biochemical abnormalities of platelets in renal failure. Evidence for decreased platelet serotonin, adenosine diphosphate and Mg-dependent adenosine triphosphatase.

Source: American Journal of Nephrology. 1(1):17-23, 1981.

Abstract: The platelet content of adenosine triphosphate (ATP), adenosine diphosphate (ADP), serotonin and ouabain-insensitive, magnesium-dependent adenosine triphosphatase (ATPase) was determined in patients with chronic renal failure, patients on chronic hemodialysis, and kidney transplant recipients. Platelet ATP content was normal in all. By contrast, ADP content, expressed in mumol/10(11) platelets, was significantly lower in renal failure: 1.82 +/- 0.96 compared to 2.51 +/- 0.97 in normals (p less than 0.05), but not in dialyzed or transplanted patients; 2.27 +/- 0.96 and 1.87 +/- 0.87, respectively. The mean content of serotonin was also significantly lower in renal failure patients: 0.52 microgram/10(9) platelets as compared to 0.90 microgram/10(9) platelets in normals (p less than 0.05) but was not significantly different in dialyzed and transplanted patients. ATPase was significantly lower in renal failure: 3.13 +/- 1.2 mumol Pi/10(9) platelets in whole suspension and 0.71 +/- 0.22 Pi/mg protein/h in membrane preparation compared to 4.74 +/- 1.1 and 1.18 +/- 0.19, respectively, in normals, and was significantly lower in dialyzed and transplanted patients. Experimental azotemia (BUN 65-86 mg/100 ml), induced by the oral ingestion of urea 2-3 g/kg body weight over 24 h, failed to induce any of these abnormalities. The abnormality in platelet ADP and serotonin content in renal failure paralleled the functional platelet defects which characterize these patients and were reversible following dialysis and transplantation. CAS Registry/EC Number 50-67-9 (Serotonin). 56-65-5 (Adenosine Triphosphate). 58-64-0 (Adenosine Diphosphate). EC 3-6-1-3 (Adenosinetriphosphatase).