Reversible Activation Defect of the Platelet Glycoprotein IIb-IIIa Complex in Patients With Uremia

Benigni, Ariela; Boccardo, Paola; Galbusera, Miriam; Monteagudo, J M; Marco, Luigi De; Remuzzi, Giuseppe; Ruggeri, Zaverio M.

doi:10.1016/s0272-6386(12)80429-x

Cited by 94 publications

(49 citation statements)

References 35 publications

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“…Although it can be argued that the concentration of FF recovered from uremic plasma was significantly higher than FF isolated from an equal volume of normal plasma, the fact that FF from identical volumes of plasma were added and that FF from uremic plasma caused inhibition is noteworthy and it further supports the hypothesis that elevated levels of FF may be partly responsible for platelet dysfunction in uremic patients. Moreover, our findings also suggest that the improvement of hemostatic function observed following HD [14,18,19,27,[35][36][37] might be due, in part, to a reduction in the circulating FF levels as a result of dialysis.…”

Section: Discussionmentioning

confidence: 89%

“…1, lanes 2 and 3). This is interesting considering the fact that an improvement in hemostatic function has been reported following HD by many investigators [14,18,19,27,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…The protamine-Sepharose beads with bound FF were then rinsed thoroughly with a washing buffer (50 mM Tris/HCl, 5 mM Na 2 EDTA, 5 mM e-amino caproic acid; pH 7.3) until no protein was detectable in the wash at 280 nm wavelength (Ultrospec III spectrophotometer, Pharmacia, Cambridge, UK). The FF adsorbed on the protamine-Sepharose were eluted with a buffer consisting of 0.2 M sodium citrate/citric acid, pH 5.3 [18,19]. The eluate was then dialyzed thrice against PBS in dialysis cassettes with molecular weight cut-off at 10,000 Da (Pierce, Rockford, IL) for 90 min to remove the citrate.…”

Section: Isolation Of Ff From Plasmamentioning

confidence: 99%

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Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb‐IIIa

et al. 2006

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Hemostatic dysfunction is frequently noted in uremia, but the mechanisms responsible for it are poorly understood and are assumed to be multifactorial. Preliminary findings from our laboratory suggest that elevated levels of circulating fibrinogen fragments (FF) might contribute to the hemostatic defect in uremic patients. Defibrinated plasma obtained from chronic hemodialysis (HD) patients as well as normal subjects were examined by SDS-PAGE and immunoblotting and quantified by an immunoassay. In addition, endogenous FF isolated from normal and uremic plasma using affinity chromatography were examined by flow cytometry for their effect on glycoprotein (GP) IIb-IIIa receptor expression and tested for their ability to inhibit platelet aggregation. The mean FF concentration in uremic plasma (1.14 ± 0.85 mg/ml) was noted to be eight times greater than in normal plasma (0.15 ± 0.01 mg/ml) (P < 0.05). Moreover, the mean FF level decreased by 48.25% following HD (from 1.14 ± 0.85 mg/ml to 0.59 ± 0.33 mg/ml; P < 0.05). SDS-PAGE and immunoblotting experiments showed that the decrease was observed in both medium-sized (20-60 kDa) as well as large (>100 kDa) FF. Further, FF isolated from uremic plasma inhibited platelet aggregation by (46.8 ± 18.1)% (P < 0.05) and the GP IIb-IIIa receptor expression by (28.0 ± 7.6)% (P < 0.05 vs. control). The results show that (1) FF levels are elevated in uremic plasma, (2) HD results in significant decrease in FF and (3) endogenous FF inhibit platelet function, presumably via competitive binding to the fibrinogen receptor GP IIb-IIIa. The decrease in plasma levels of FF > 100 kDa following HD suggests that adsorption to the dialysis membrane contributes to their removal. Am. J. Hematol. 81:915-926, 2006. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 89%

“…1, lanes 2 and 3). This is interesting considering the fact that an improvement in hemostatic function has been reported following HD by many investigators [14,18,19,27,[35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Ff From Plasmamentioning

confidence: 99%

See 1 more Smart Citation

Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb‐IIIa

et al. 2006

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“…3 In studies conducted with uremic patients, platelet dysfunction,as well as intrinsic platelet defects and abnormal platelet endothelial interactions have been shown. 4,5 Mild thrombocytopenia may be seen in some uremic patients. 6 Patients with CKD have also been shown to have reduced leukocyte activity.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13][14][15][16][17][18][19] The results of these studies suggest that metabolic acidosis in chronic kidney disorease may be associated with hematological changes in these patients either by contributing to the progression of the disease or by its pathophysiological effects. Treating metabolic acidosis with oral sodium bicarbonate was predicted to prevent these hematological 1 Internal Medicine Clinic, 2 Internal Medicine Clinic, 3 Internal Medicine Clinic, 4 Nephrology Clinic, Adana Numune Health Training and Research Center, University of Health Sciences, Adana, 5 Internal Medicine Clinic, 6 Internal Medicine Clinic, Istanbul Haseki Health Training and Research Center, University of Health Sciences, Istanbul, Turkey abnormalities. 20 Studies that examine the relationship between metabolic acidosis and hematologic changes in CKD are limited in the literature.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Oral Sodium Bicarbonate Treatment on Hematological Parameters in Patients with Chronic Kidney Disease During the Predialysis Period

Saler¹,

Bankır²,

Duman³

et al. 2018

IJCMR

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Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment

et al. 2002

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Relatively little is known concerning the magnitude of alterations of platelet activation and secretion markers of patients with major depression when compared to patients at increased risk for, or with current, clinically significant atherosclerosis. Markers of in vivo platelet stimulation and secretion were measured under basal conditions in normal comparison subjects (n = 12) and three patient groups: patients diagnosed with DSM-IV major depression (n = 15), dialysis-dependent patients (n = 12), and patients with severe thoracic aortic atherosclerosis (n = 10). In comparison to normal comparison subjects, depressed patients and patients with thoracic aortic atherosclerosis exhibited the greatest platelet stimulation as detected by increased anti-LIBS platelet binding. Dialysis-dependent patients exhibited the highest plasma concentrations of the renally-excreted platelet-specific secretion protein, beta-thromboglobulin. This study extends previous observations of increased platelet activation in patients with major depression and documents similar alterations in patients with transesophageal echocardiography (TEE)-documented thoracic aortic atherosclerosis. Future studies will determine whether the magnitude of platelet stimulation and secretion in patients with comorbid depression and atherosclerotic aortic disease is greater than that observed in nondepressed patients with atherosclerotic aortic disease or major depression alone. These findings provide further evidence for either increased platelet activation and/or intrinsic heightened platelet reactivity as one of the biological substrates underlying the increased risk of depressed patients for cardiovascular disease.

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Reversible Activation Defect of the Platelet Glycoprotein IIb-IIIa Complex in Patients With Uremia

Cited by 94 publications

References 35 publications

Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb‐IIIa

Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb‐IIIa

The Effects of Oral Sodium Bicarbonate Treatment on Hematological Parameters in Patients with Chronic Kidney Disease During the Predialysis Period

Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment

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