Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients
Benoit, Stephen E.
Michelson, Alan D.
UMass Chan AffiliationsDepartment of Pediatrics
Platelet Aggregation Inhibitors
Platelet Glycoprotein GPIb-IX Complex
MetadataShow full item record
AbstractA bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P andlt; 0.001) than either healthy controls (120+/-4 fluorescent units; P andlt; 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P andlt; 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P andlt; 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P andlt; 0.05) or peritoneal dialysis patients (62+/-2; P andlt; 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.
SourceAm J Kidney Dis. 1998 Jul;32(1):132-8. doi 10.1053/ajkd.1998.v32.pm9669434
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43382
Related ResourcesLink to article in PubMed
Showing items related by title, author, creator and subject.
Evaluation of platelet function by flow cytometryMichelson, Alan D.; Barnard, Marc R.; Krueger, Lori A.; Frelinger, Andrew L. III; Furman, Mark I. (2000-07-01)Platelet function in whole blood can be comprehensively evaluated by flow cytometry. Flow cytometry can be used to measure platelet reactivity, circulating activated platelets, platelet-platelet aggregates, leukocyte-platelet aggregates, procoagulant platelet-derived microparticles, and calcium flux. Clinical applications of whole blood flow cytometric assays of platelet function in disease states (e.g., acute coronary syndromes, angioplasty, and stroke) may include identification of patients who would benefit from additional antiplatelet therapy and prediction of ischemic events. Circulating monocyte-platelet aggregates appear to be a more sensitive marker of in vivo platelet activation than circulating P-selectin-positive platelets. Flow cytometry can also be used in the following clinical settings: monitoring of GPIIb-IIIa antagonist therapy, diagnosis of inherited deficiencies of platelet surface glycoproteins, diagnosis of storage pool disease, diagnosis of heparin-induced thrombocytopenia, and measurement of the rate of thrombopoiesis.
In vitro testing of fresh and lyophilized reconstituted human and baboon plateletsValeri, C. Robert; Macgregor, Hollace; Barnard, Marc R.; Summaria, L.; Michelson, Alan D.; Ragno, G. (2004-10-01)BACKGROUND: Studies have been performed on human fresh, liquid-preserved, and cryopreserved platelets (PLTs) to assess PLT-adhesive surface receptors, PLT membrane procoagulant activity, PLT aggregation, and thromboxane production. Lyophilization has been developed as a method to preserve PLTs. This study was performed to evaluate these measurements on human and baboon fresh and lyophilized reconstituted PLTs. STUDY DESIGN AND METHODS: In both human and baboon fresh and lyophilized PLTs, aggregation response and PLT production of thromboxane A2 were measured after stimulation, and PLT surface markers P-selectin, glycoprotein (GP) Ib, GPIIb-IIIa, and factor (F) V were measured before and after stimulation. RESULTS: Fresh PLTs responded to the dual agonists arachidonic acid and adenosine diphosphate (ADP) to aggregate and produce thromboxane A2, and in both the PLT surface markers P-selectin and GPIIb-IIIa increased and GPIb decreased after stimulation. Neither human nor baboon lyophilized reconstituted PLTs aggregated to dual agonists, and neither produced thromboxane A2, increased PLT surface markers P-selectin or GPIIb-IIIa, or decreased PLT GPIb after stimulation. Nevertheless, after recalcification the lyophilized reconstituted PLTs accumulated FV to a significantly greater degree than fresh PLTs. CONCLUSIONS: Lyophilized reconstituted PLTs exhibited modification of the PLT membrane that interfered with aggregation and thromboxane production, prevented increases in PLT P-selectin and GPIIb-IIIa and decreases in GPIb after stimulation, and increased FV accumulation after recalcification. The in vitro data suggest that lyophilized PLTs may have reduced in vivo survival. In vivo studies are needed to determine the survival and function of lyophilized PLTs.