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Biomedical subjects

A D Michelson

Publications and source records attributed to A D Michelson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Evaluation of platelet function by flow cytometry.

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.

Antibodies, Monoclonal↗
PubMed2000

Antithrombotic therapy in the cardiac catheterization laboratory: focus on antiplatelet agents.

Pharmacologic advances in the use of antithrombotic agents have paralleled the technologic innovations used in patients undergoing coronary interventions. The recognition of the central role of platelets in the development of complications related to coronary interventions led to the investigation and subsequent routine use of several antiplatelet agents as adjuvants to coronary intervention. Thus, the oral agents aspirin and either ticlopidine or clopidogrel are routinely administered after coronary stenting. Intravenous glycoprotein (GP) IIb/IIIa antagonists have been extensively studied and reduce adverse cardiac events in patients undergoing coronary interventions, especially those receiving intracoronary stents. Despite the growing use of GP IIb/IIIa antagonists, much information remains unknown as to the proper dosing and the effects these agents have on other elements of the hemostatic and vascular systems.

Abciximab↗
PubMed2000

Flow cytometric analysis of platelets.

BACKGROUND AND OBJECTIVES: Despite recent progress in our understanding of platelet function in vitro, there remains a remarkable paucity of methods to study platelet function in vivo. MATERIALS AND METHODS: We have developed novel three color whole blood flow cytometric methods for tracking of infused platelets and measurement of their function in vivo. RESULTS: These methods were used to demonstrate that circulating P-selectin-positive (degranulated) platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function. CONCLUSIONS: 1) These studies strongly suggest that the measurement of platelet surface P-selectin in platelet concentrates stored in the blood bank should not be used as a predictor of platelet survival or function in vivo. 2) The described methods provide the means to answer many previously difficult to address questions about in vivo platelet function in transfusion medicine.

Animals↗
PubMed2000

GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood.

In addition to inhibition of platelet aggregation, GPIIb-IIIa antagonists may reduce thrombotic events via other mechanisms. In a novel whole blood flow cytometric system, we investigated the effects of GPIIb-IIIa antagonists, in the presence or absence of thrombin inhibitors, on platelet surface-bound factor V/Va and platelet surface phospholipids. Diluted venous blood was incubated with either buffer or a GPIIb-IIIa antagonist (abciximab, tirofiban, or eptifibatide). Some samples were pre-incubated with clinically relevant concentrations of unfractionated heparin (UFH), a low molecular weight heparin, a direct thrombin inhibitor, or buffer only. Platelets were then activated and labeled with mAb V237 (factor V/Va-specific) or annexin V (binds phosphatidylserine), fixed, and analyzed by flow cytometry. In the absence of thrombin inhibitors, GPIIb-IIIa antagonists (especially abciximab) significantly reduced agonist-induced platelet procoagulant activity, as determined by reduced binding of V237 and annexin V. At high pharmacologic concentrations, unfractionated heparin and enoxaparin, but not hirudin, further reduced factor V/Va binding to the surface of activated platelets in the presence of GPIIb-IIa antagonists. Agonist-induced platelet procoagulant activity was reduced in a patient with Glanzmann's thrombasthenia. We conclude that GPIIb-IIIa antagonists reduce platelet procoagulant activity in whole blood and heparin and enoxaparin augment this reduction. Fibrinogen binding to GPIIb-IIIa is important in the generation of platelet procoagulant activity.

Abciximab↗
PubMed2000

Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.

Platelet-derived microparticles (PDMP) appear to play a major role in the generation of procoagulant activity. In this study, we describe a novel flow cytometric method that allows direct evaluation of the procoagulant activity of PDMP and platelets in the physiological milieu of whole blood. The percent PDMP generated in response to calcium ionophore A23187 and calcium was increased in preterm neonates (67.5+/-3.4%, mean +/- S.E.M., n = 8, p <0.05) and term neonates (67.2+/-2.7%, n = 7, p<0.05) compared with adults (49.5+/-3.4%, n = 13). However, in preterm neonates A23187/calcium-induced binding of factor V/Va to PDMP and platelets (22.8+/-5.6 fluorescence units) was markedly reduced (p <0.05) compared to term neonates (58.2+/-7.2) and adults (50.6+/-6.3). In preterm blood, A23187/calcium-induced binding of factor V/Va to PDMP and platelets returned to adult levels when: a) adult plasma, rather than autologous preterm neonatal plasma, was added; or b) factor V, but not factor VIII, was added to autologous preterm neonatal plasma. In summary: 1) We have developed a flow cytometric method for the direct detection of procoagulant PDMP and platelets in whole blood. 2) Compared to adults and term neonates, PDMP and platelets of preterm neonates bound markedly less factor V/Va (reflecting reduced procoagulant activity), because of a relative lack of factor V in preterm neonates. 3) This procoagulant defect in PDMP and platelets may contribute to the propensity of preterm neonates, but not term neonates, to intraventricular hemorrhage. 4) The percent PDMP does not necessarily reflect the degree of procoagulant activity of PDMP or platelets.

Adult↗
PubMed2000

The cleaved peptide of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the surface-connected canalicular system.

The only known function of the 41 amino acid cleaved peptide (TR1-41) of the seven transmembrane domain thrombin receptor (PARI) is to activate platelets (as determined by aggregation, surface P-selectin, and fibrinogen binding to activated GPIIb-IIIa). We now demonstrate that TR1-41 results in a concentration-dependent decrease in the platelet surface expression of each component of the GPIb-IX-V complex, as determined by flow cytometry with a panel of monoclonal antibodies (including 6D1, directed against the von Willebrand factor binding site on GPIbalpha, and TM60, directed against the thrombin binding site on GPIbalpha). TR1-41 also decreased ristocetin-induced platelet agglutination. Immunoblotting after incubation of platelets with TR1-41 revealed neither a loss of platelet GPIb nor increase in supernatant GPIb fragments. As demonstrated by immunoelectron microscopy, TR1-41 resulted in a redistribution of GPIb, GPIX, and GPV from the platelet surface to the surface-connected canalicular system (SCCS). In summary, the cleaved peptide (TR1-41) of PAR1 results in a redistribution of the platelet surface GPIb-IX-V complex to the SCCS, thereby negatively regulating the GPIbalpha binding sites for von Willebrand factor and thrombin.

Animals↗
PubMed1999

Comparison of the effects of transfusions of cryopreserved and liquid-preserved platelets on hemostasis and blood loss after cardiopulmonary bypass.

OBJECTIVE: The aim of the study was to compare the clinical effects and hemostatic efficiency of transfusions of platelets preserved in the frozen state for as long as 2 years with transfusions of platelets preserved in the conventional manner for as long as 5 days in patients undergoing cardiopulmonary bypass. METHODS: Seventy-three patients were prospectively randomly assigned to receive transfusions of cryopreserved or liquid-preserved platelets. Nonsurgical blood loss was measured during and after the operation. Bleeding time, hematologic variables, and the bleeding time site shed blood were assayed before cardiopulmonary bypass and at 30 minutes and 2, 4, and 24 hours after transfusion. In vitro platelet function tests were conducted on platelets obtained from healthy volunteers. RESULTS: No adverse sequelae of the transfusions were observed. Blood loss and the need for postoperative blood product transfusions were lower in the group receiving cryopreserved platelets. Lower posttransfusion platelet increments and a tendency toward decreased platelet survival were observed in patients receiving cryopreserved platelets. Hematocrit and plasma fibrinogen were significantly higher in this group, and the duration of intubation was shorter. In vitro, cryopreserved platelets demonstrated less aggregation, lower pH, and decreased response to hypotonic stress but generated more procoagulant activity and thromboxane. CONCLUSIONS: (1) Cryopreserved platelet transfusions are superior to liquid-preserved platelets in reducing blood loss and the need for blood product transfusions after cardiopulmonary bypass. (2) The reduction in blood loss in the patients receiving cryopreserved platelet transfusions after cardiopulmonary bypass probably reflects improved in vivo hemostatic function of cryopreserved platelets. (3) Some in vitro measures of platelet quality (aggregation, pH, hypotonic stress) may not reflect in vivo quality of platelet transfusions after cardiopulmonary bypass, whereas other in vitro measures (platelet procoagulant activity and thromboxane) do.

Aged↗
PubMed1999

Chronic venous insufficiency is associated with increased platelet and monocyte activation and aggregation.

PURPOSE: This study assessed whether the increased numbers of platelet-monocyte aggregates observed in patients with venous stasis ulceration (VSU) represent a response to dermal ulceration or if it is a condition associated with underlying chronic venous insufficiency (CVI). We also analyzed the expression of CD11b in patients with CVI to determine whether leukocyte activation, known to occur in VSU, is a precursor of or a response to ulceration. METHODS: Patients with varying classes of CVI (n = 24) and healthy control subjects (n = 15), whose status was documented by means of duplex scanning, stood upright and stationary for 10 minutes. Two aliquots of blood, drawn from a distal leg vein and an antecubital fossa vein, were incubated with either buffer or one of three platelet agonists. After fixation, these samples were further incubated with fluorescent-labeled monoclonal antibodies (f-MoAb) specific for CD14 (monocytes) and CD61 (platelets). The activated leukocyte assay was performed by incubating another aliquot of the blood samples with f-MoAb specific for CD11b and CD14. All samples were evaluated by means of flow cytometry. RESULTS: We observed significantly more platelet-monocyte aggregates throughout the circulation in patients with CVI than in control subjects (29% vs. 8%; P <.0002). Furthermore, patients with CVI formed significantly more of these aggregates in response to all platelet agonists than did control subjects. There were no significant differences between baseline numbers of aggregates or response to agonists in patients who had CVI with (n = 10) or without (n = 14) ulceration. Patients with CVI had more circulating platelet-neutrophil aggregates than control subjects (7.2% vs. 3.6%; P =.05). The addition of platelet agonists to the blood of patients with CVI resulted in more platelet-neutrophil aggregates than in control subjects. Monocyte CD11b expression was higher in patients with CVI than in control subjects (7.5 vs. 3.7; P <.01), with no differences noted in CD11b expression between patients with or without ulceration. Neutrophil CD11b expression was low and similar in control subjects and patients with CVI. CONCLUSION: All classes of CVI are associated with significantly increased percentages of platelet-monocyte aggregates and increased percentages of platelet-neutrophil aggregates throughout the circulation. The presence of more of these aggregates and the increased propensity to form aggregates in the presence of platelet agonists in all classes of CVI suggests an underlying state of platelet activation and increased reactivity that is independent of the presence of ulceration. The increased expression of monocyte CD11b throughout the circulation in all classes of CVI suggests that although systemic monocyte activation occurs in CVI, its presence is independent of VSU as well.

Adult↗
PubMed1999

The effects of aspirin and hypothermia on platelet function in vivo.

Patients undergoing hypothermic cardiopulmonary bypass are often receiving aspirin therapy. Hypothermia, aspirin and cardiopulmonary bypass can each induce a platelet function defect, but it is not known if the effects of aspirin and hypothermia are additive in this regard. To address this question in humans in vivo, the forearm skin temperature of healthy volunteers was equilibrated and maintained at either normothermia (32 degrees C) or hypothermia (28 degrees C or 22 degrees C) before and 16 h after the ingestion of 650 mg aspirin. A standardized template bleeding time was performed on the forearm and the shed blood emerging from the wound was assayed for platelet surface P-selectin expression by whole blood flow cytometry (reflecting alpha granule secretion) and thromboxane B2 (the stable metabolite of thromboxane A2) by radioimmunoassay. Hypothermia resulted in marked prolongation of the bleeding time. Aspirin resulted in prolongation of the bleeding time under normothermic conditions, but only minimally augmented the hypothermia-induced prolongation of the bleeding time. Platelet surface P-selectin up-regulation in shed blood was abolished by hypothermia. Aspirin had no effect on maximal platelet surface P-selectin expression under normothermic or hypothermic conditions. Both hypothermia and aspirin resulted in markedly reduced shed blood thromboxane B2. Although aspirin slightly augmented the hypothermia-induced reduction in shed blood thromboxane B2, the concentration of thromboxane generated in shed blood under hypothermic conditions in the absence of aspirin had no effect on platelet surface P-selectin or platelet aggregation in whole blood. In conclusion, as determined by three independent parameters of the shed blood emerging from a standardized bleeding time wound (bleeding time, platelet surface P-selectin, and thromboxane B2), aspirin did not significantly augment hypothermia-induced platelet dysfunction in vivo.

Aspirin↗
PubMed1999

Platelet surface p-selectin, platelet-granulocyte heterotypic aggregates, and plasma-soluble p-selectin during plateletpheresis.

BACKGROUND: Plateletpheresis components have been shown to contain p-selectin-positive platelets after collection and storage. P-selectin mediates binding of activated platelets to granulocytes and monocytes. This study was undertaken to assess platelet activation, granulocyte activation, platelet-granulocyte heterotypic aggregate formation, and the plasma-soluble p-selectin level during plateletpheresis performed on a particular instrument (MCS+, Haemonetics). STUDY DESIGN AND METHODS: Flow cytometry was used to assay platelet surface p-selectin, granulocyte iC3b receptor, and platelet-granulocyte aggregates in the platelet component, residual blood in the disposable polycarbonate bowl of the MCS+, and in the donor blood with and without the addition of in vitro agonists before, during, and after plateletpheresis. The plasma-soluble p-selectin levels in the platelet component, disposable bowl, and donor venous blood were measured by an enzyme-linked immunosorbent assay. RESULTS: Levels of p-selectin-positive platelets, activated granulocytes, and platelet-granulocyte aggregates were greater in the disposable bowl than in the preapheresis donor blood. Levels of p-selectin-positive platelets, activated granulocytes, and platelet-granulocyte aggregates in the postapheresis donor blood were similar to those in the preapheresis donor blood. The platelet components contained no activated granulocytes or detectable platelet-granulocyte heterotypic aggregates, and only about 10-percent activated platelets. The plasma-soluble p-selectin level in the platelet component was significantly greater than that in the preapheresis donor blood, the residual blood in the disposable bowl, or the postapheresis donor blood. CONCLUSIONS: Measurements of platelet surface p-selectin, platelet-granulocyte heterotypic aggregates, and plasma-soluble p-selectin can be used to detect platelet activation during plateletpheresis.

Antibodies, Heterophile↗
PubMed1999

Fresh, liquid-preserved, and cryopreserved platelets: adhesive surface receptors and membrane procoagulant activity.

BACKGROUND: A study in humans showed that the transfusion of previously frozen human platelets after cardiopulmonary bypass, despite decreased survival, resulted in better hemostatic function than that of liquid-preserved platelets stored at 22 degrees C for 3 to 4 days. STUDY DESIGN AND METHODS: In this study, fresh, 3- to 4-day-old liquid-preserved, and cryopreserved human platelets were studied by the use of monoclonal antibodies directed against p-selectin, glycoprotein (GP)Ib, activated GPIIb/IIIa, and coagulation factor V in a three-color flow cytometric method. RESULTS: The fresh and liquid-preserved platelets had normal surface levels of GPIb, while the cryopreserved platelets were composed of distinct subpopulations of GPIb-normal and GPIb-reduced platelets. On the basis of the binding of factor V, both subpopulations of cryopreserved platelets exhibited greater surface binding of factor V than did fresh and liquid-preserved platelets. Activated GPIIb/IIIa was elevated on GPIb-normal platelets, but not on GPIb-reduced platelets. Baboon platelets frozen by a procedure identical to that used to freeze human platelets also had GPIb-normal and GPIb-reduced subpopulations after the freezing-thawing-washing procedure. Autologous cryopreserved baboon platelets labeled with biotin-X-N-hydroxysuccinimide showed a rapid removal of GPIb-reduced platelets during the 5-minute postinfusion period, whereas GPIb-normal platelets had an in vivo recovery of 48 percent and a lifespan of slightly less than 6 days. CONCLUSIONS: Improved in vivo function of cryopreserved platelets may be related to the rapid hemostatic effect of the GPIb-reduced subpopulation secondary to increased binding of factor V and expression of p-selectin.

Animals↗
PubMed1999

Laboratory markers of platelet activation and their clinical significance.

Whole blood flow cytometry is a powerful new laboratory technique for assessment of platelet activation and function. Flow cytometry can be used to measure platelet hyperreactivity, circulating activated platelets, leukocyte-platelet aggregates, and procoagulant platelet-derived microparticles in a number of clinical settings, including acute coronary syndromes, angioplasty, cardiopulmonary bypass, acute cerebrovascular ischemia, peripheral vascular disease, diabetes mellitus, preeclampsia, and Alzheimer's disease. Clinical applications of whole blood flow cytometric assays of platelet function in these diseases 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 glycoprotein IIb-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.

Biomarkers↗
PubMed1998

The cleaved peptide of the thrombin receptor is a strong platelet agonist.

Thrombin cleaves its G-protein-linked seven-transmembrane domain receptor, thereby releasing a 41-aa peptide and generating a new amino terminus that acts as a tethered ligand for the receptor. Peptides corresponding to the new amino terminal end of the proteolyzed seven-transmembrane domain thrombin receptor [TR42-55, SFLLRNPNDKYEPF, also known as TRAP (thrombin receptor-activating peptide)], previously have been demonstrated to activate the receptor. In this study, we demonstrate that the 41-aa cleaved peptide, TR1-41 (MGPRRLLLVAACFSLCGPLLSARTRARRPESKATNATLDPR) is a strong platelet agonist. TR1-41 induces platelet aggregation. In whole-blood flow cytometric studies, TR1-41 was shown to be more potent than TR42-55 and almost as potent as thrombin, as determined by the degree of increase in: (i) platelet surface expression of P-selectin (reflecting alpha granule secretion); (ii) exposure of the fibrinogen binding site on the glycoprotein (GP) IIb-IIIa complex; and (iii) fibrinogen binding to the activated GPIIb-IIIa complex. As determined by experiments with inhibitors [prostaglandin I2, staurosporine, wortmannin, the endothelium-derived relaxing factor congener S-nitroso-N-acetylcysteine (SNAC), EDTA, EGTA, and genestein], and with Bernard-Soulier or Glanzmann's platelets, we demonstrated that TR1-41-induced platelet activation is: (i) inhibited by cyclic AMP; (ii) mediated by protein kinase C, phosphatidyl inositol-3-kinase, myosin light chain kinase, and intracellular protein tyrosine kinases; (iii) dependent on extracellular calcium; and (iv) independent of the GPIb-IX and GPIIb-IIIa complexes. TR1-41-induced platelet activation was synergistic with TR42-55. In summary, the cleaved peptide of the seven-transmembrane domain TR (TR1-41) is a strong platelet agonist.

Amino Acid Sequence↗
PubMed1998

Guidelines for antithrombotic therapy in pediatric patients.

Because of the relatively low incidence of TEs in children, the diagnostic and therapeutic approaches used are largely extrapolated from guidelines for adults. Features that differ in children compared with adults include underlying disorders, high incidence of CVL-related DVT in the upper venous system, and response to SH, warfarin, and thrombolytic agents. There is a paucity of information on the risk/benefit ratio of the therapeutic interventions and long-term outcome. Clinical trials are urgently needed to clarify optimal management for pediatric patients with TEs.

Causality↗
PubMed1998

Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease.

OBJECTIVES: We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates. BACKGROUND: Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis. METHODS: Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry. RESULTS: Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p < 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 vs. 16.1 +/- 2.2, p < 0.01), 1 micromol/liter of ADP/epinephrine (51.4 +/- 4.6 vs. 37.5 +/- 3.8, p < 0.05) or 5 micromol/liter of thrombin receptor agonist peptide (TRAP) (65.7 +/- 6.8 vs. 20.2 +/- 5.1, p < 0.01). Patients with stable CAD also had increased circulating monocyte-platelet aggregates compared with control subjects (percent platelet-positive monocytes: 15.3 +/- 3.0 vs. 6.3 +/- 0.9, p < 0.01). Furthermore, patients with stable CAD formed more monocyte-platelet aggregates than did control subjects when their whole blood was stimulated with 1 micromol/liter of ADP (50.4 +/- 4.5 vs. 28.1 +/- 5.3, p < 0.01), 1 micromol/liter of ADP/epinephrine (60.7 +/- 4.3 vs. 48.0 +/- 4.8, p < 0.05) or 5 micromol/liter of TRAP (67.6 +/- 5.7 vs. 34.3 +/- 7.0, p < 0.01). CONCLUSIONS: Patients with stable CAD have circulating activated platelets, circulating monocyte-platelet aggregates, increased platelet reactivity and an increased propensity to form monocyte-platelet aggregates.

Adenosine Diphosphate↗
PubMed1998

Patients with venous stasis ulceration have increased monocyte-platelet aggregation.

PURPOSE: Leukocyte activation has been implicated in the pathogenesis of venous stasis ulceration, but the involvement of activated platelets and leukocyte-platelet aggregates has not been previously investigated. The purpose of this study was to determine whether patients with venous stasis ulceration have increased platelet activation and a propensity toward formation of leukocyte-platelet aggregates. METHODS: Blood was drawn from the superficial veins of the leg just proximal to a venous stasis ulcer and from an antecubital vein in 14 patients with venous stasis ulceration. Blood was also drawn from the antecubital vein of 14 volunteers without evidence of venous disease. Whole-blood flow cytometry was used to analyze the samples before and after activation with a panel of agonists for evidence of platelet activation and the formation of leukocyte-platelet aggregates. RESULTS: Patients with venous stasis ulceration had a greater number of monocyte-platelet aggregates in both the arm and leg samples than did the control subjects (p < 0.01). Furthermore, antecubital blood samples from patients with venous stasis ulceration stimulated with either thrombin-receptor agonist peptide, adenosine diphosphate, or phorbol myristate acetate formed more monocyte-platelet aggregates than did control samples (p < 0.05). No differences in platelet activation or neutrophil-platelet aggregate formation were noted among the three sample groups. CONCLUSIONS: Patients with venous stasis ulceration have an increase in the number of monocyte-platelet aggregates in systemic venous blood as well as in venous blood adjacent to a venous stasis ulcer, implicating the monocyte as the leukocyte involved in the pathogenesis of venous stasis ulceration. No association was identified between the presence of a venous stasis ulcer and either neutrophil-platelet aggregation or the activation of individual platelets. Because platelet activation is necessary for the formation of monocyte-platelet aggregates, these data also suggest that monocyte-platelet aggregation is a more sensitive marker for in vivo platelet activation than is the identification of individual activated platelets.

Adenosine Diphosphate↗
PubMed1998

Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients.

A 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 < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 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 < 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 < 0.05) or peritoneal dialysis patients (62+/-2; P < 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.

Blood Platelets↗