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PubMed1983

A new congenital defect of platelet secretion: impaired responsiveness of the platelets to cytoplasmic free calcium.

A 16-year-old boy with a bleeding disorder since infancy has a long bleeding time, normal platelet count and morphology and normal plasma factor-VIII activities. His platelets undergo normal shape change and primary aggregation in response to ADP but show defective 5-hydroxytryptamine (5-HT) secretion and aggregation in response to adrenaline, sodium arachidonate, U44069, PAF-acether, A23187 and low concentrations of collagen. Thrombin and higher concentrations of collagen produce a normal response. Secretion of beta-thromboglobulin and platelet factor 4 parallels that of 5-HT. Thromboxane B2 is produced normally in response to exogenous arachidonate and to stimulation by thrombin, collagen and A23187 in all concentrations tested. The patient's endoperoxides and thromboxane A2 aggregate aspirin-treated platelets, though his platelets are themselves unresponsive. Cyclic AMP is present at normal concentration in the patient's unstimulated platelet-rich plasma, and PGI2 inhibits platelet aggregation by ADP and thrombin in a normal dose-related plasma, and PGI2 inhibits platelet aggregation by ADP and thrombin in a normal dose-related manner. Platelet ultrastructure, 5-HT uptake and content of adenine nucleotides, platelet factor 4 and beta-thromboglobulin are all within normal limits. When the patient's platelets were loaded with the fluorescent dye quin 2, which serves as an indicator of cytoplasmic free calcium ions, their responses to thrombin, whether in the presence or virtual absence of extracellular Ca2+, were entirely normal in respect of free calcium ions, secretion, shape-change and aggregation. In response to ionomycin, however, a normal increase in free calcium ions was accompanied by normal shape-change but virtually no aggregation or 5-HT secretion. The platelet calmodulin content was normal. These findings show that the defect in this patient's platelets is of utilization of cytoplasmic Ca2+ for secretion and aggregation, rather than of Ca2+ uptake or mobilization of Ca2+ from intracellular storage sites. It is suggested that the most likely site of the defect is the phosphorylation of one of the proteins concerned in the secretory mechanism.

Adolescent↗
PubMed1990

Calpain proteolysis of von Willebrand factor enhances its binding to platelet membrane glycoprotein IIb/IIIa: an explanation for platelet aggregation in thrombotic thrombocytopenic purpura.

We have previously observed calpain activity (calcium-dependent cysteine protease) in sera from patients with acute thrombotic thrombocytopenic purpura (TTP). The calpain activity was not present following recovery and was not detected in other thrombocytopenic disorders. We postulated that this enzyme could participate in the pathogenesis of TTP. Because other investigators have demonstrated abnormalities of von Willebrand factor (vWF) in patients with TTP, we proposed that calpain might interact with vWF in TTP. To challenge this hypothesis, we measured the binding of untreated and calpain-treated vWF to normal and ADP or calpain activated platelets. Untreated vWF bound in a specific and saturable fashion to activated platelets, but only at low (30 microM) calcium concentrations. Von Willebrand factor did not bind to activated platelets at physiological (2 mM) calcium concentrations. Calpain proteolysis of vWF changed the binding characteristics of the vWF so that it had greatly increased binding to both ADP and calpain activated platelets. The calpain-proteolyzed vWF bound to activated platelets at both low and physiological calcium concentrations, and was capable of causing platelet aggregation. The calpain-proteolyzed vWF bound to the activated platelets via glycoproteins IIb/IIIa as demonstrated by inhibition studies using monoclonal antibodies against glycoproteins IIb/IIIa and Ib. It also had a high binding affinity and was capable of inhibiting the binding of radiolabelled fibrinogen to the activated platelets at physiological calcium concentrations. Calpain also proteolyzed fibrinogen, but the calpain altered fibrinogen had normal platelet reactivity. These studies provide further insight into the pathogenesis of the platelet aggregation of thrombotic thrombocytopenic purpura. Calpain proteolyses vWF and can produce the characteristic loss of large multimers seen on sodium dodecyl sulphate (SDS)-agarose gel electrophoresis. The altered vWF is highly reactive with activated platelets and binds to platelet glycoproteins IIb/IIIa and participates in formation of the platelet aggregates that characterize this disease.

Binding, Competitive↗
PubMed1991

Platelet-leukocyte interaction in adhesion to endothelial cells induced by platelet-activating factor in vitro.

1. Platelet-activating factor (PAF, 10 nM) did not induce platelet adhesion to endothelial cells cultured in monolayer but it induced their adhesion to protein-coated plastic. However, PAF induced a marked platelet adhesion to endothelial cells when polymorphonuclear leukocytes (PMNs) were present. Lyso-PAF had no effect. 2. Phase-contrast microscopic examination showed that single platelets rather than their aggregates adhered to the endothelial cell surface around aggregating and adhering PMNs. 3. Significant platelet adhesion was induced by PAF at concentrations higher that 0.01 nM with the maximal response at 10 nM. Platelet adhesion occurred within minutes after PAF addition, reaching a maximum approximately after 30 min. Platelet adhesion also occurred significantly at a PMN:platelet ratio of 1:800, and linearly up to 1:50. 4. The PAF-induced platelet adhesion was suppressed by three structurally unrelated PAF antagonists, WEB 2086, ONO 6240 and BN 52021, in a concentration-dependent manner. 5. PAF also increased PMN adhesion to endothelial cell monolayers, which was further augmented by the presence of platelets. 6. The present study demonstrates that PAF induces platelet adhesion to endothelial cells in vitro when PMNs are present and that there is a close interaction between platelets and PMNs in their adhesion to endothelial cells. The present study further suggests that PMNs could play a central role in platelet adhesion to vascular endothlium in certain pathological conditions.

Adenine↗
PubMed1985

Response to platelet-activating factor of platelets from patients with multiple sclerosis.

The response of Multiple Sclerosis (MS) and control platelets to different concentrations of platelet-activating factor was studied. At concentrations in the range 10(-7) to 10(-5)M, it was found that the MS platelets tended to aggregate fully at lower concentrations than was the case with control platelets. At a concentration of 10(-6)M, it was found that in 19 cases the MS platelets gave a full aggregation response whilst 4 cases showed biphasic but full aggregation, whereas at this concentration the control platelets showed full aggregation in only 2 cases, biphasic but less complete aggregation in 5 cases and reversible aggregation in 16 cases. In crossover studies, it could be shown that MS platelets resuspended in control platelet-poor plasma still showed enhanced aggregability and that the response of control platelets was unaffected by resuspension in MS platelet-poor plasma. Differences were also seen in susceptibility of platelets of MS and control subjects to inhibition by indomethacin, bromophenacyl bromide (a phospholipase inhibitor) and verapamil (a Ca2+ antagonist). It is suggested that the hyperaggregability of the MS platelets could reside in the platelets themselves, and may be associated with enhanced phospholipase activity.

Acetophenones↗
PubMed2004

The role of platelets and recombinant factor VIIa on thrombin generation, platelet activation and clot formation.

In the present study we assessed the effect of platelet counts and rFVIIa on thrombin generation, platelet activation and clot formation after tissue factor pathway activation in human plasma aiming to investigate the mechanism by which rFVIIa induces haemostasis in patients with severe thrombocytopenia. Plasma samples with platelet counts from 5 x 10(9)/l to 150 x 10(9)/l were spiked with rFVIIa (1 micro g/ml) or buffer. Clotting was initiated in the presence of diluted thromboplastin. Thrombin generation was assessed using the Thrombogram-Thrombinoscope trade mark assay. The kinetics of platelet activation was assessed using flow cytometry to measure the expression the P-selectin on platelet membrane of washed platelets suspended in defibrinated homologous PPP. Thromboelastography was used to evaluate the effect of platelets and rFVIIa on the kinetics of clot formation and clot's firmness. In the presence of low platelet counts the endogenous thrombin potential (ETP) and the maximum concentration of generated thrombin (Cmax) were reduced by 60%-70%. The lag-time of thrombin generation and the time required to reach the Cmax (Tmax) were prolonged, the velocity of platelet activation was decreased and thrombus formation was delayed. Recombinant FVIIa accelerated thrombin generation and platelet activation but it did not significantly modify ETP or Cmax. Recombinant FVIIa enhanced platelet activation in a TF and thrombin dependent manner since its effect on the studied parameters was abolished when TF was omitted or when hirudin was added into the experimental system respectively. Recombinant FVIIa normalized the velocity of clot formation but it did not modify clot firmness, which depended mainly on platelets' count. In conclusion, in experimental conditions simulating severe thrombocytopenia rFVIIa in the presence of low amounts of TF, accelerates thrombin generation, without increasing the maximum amount of generated thrombin, thus leading in enhanced platelet activation and rapid clot formation.

Blood↗
PubMed2004

Comparison of two methods to assess variability of platelet response to anti-platelet therapies in patients with acute coronary syndrome undergoing angioplasty.

The study investigated the clinical usefulness of a new method to evaluate platelet activation and the variability of platelet response to anti-platelet therapy in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Platelet activation was assessed in parallel by a new method for platelet density measurements (MPC, Mean Platelet Component Concentration), on the automated ADVIA 120 Hematology System and by the classic measurement of P-selectin (CD62P) expression, on a fluorescence flow cytometer. Patients received a loading dose of clopidogrel (300 mg; n = 29) or a bolus of abciximab (0.25 mg/kg; n = 15). Blood samples were collected before (baseline) and at different times after PTCA and antiplatelet drugs administration. Our data showed a close inverse correlation between the change in MPC and the CD62P fluorescence surface marker expression (r = -0.776, P<0.0001). Individual platelet activation determinations in patients receiving either clopidogrel or abciximab showed a variation in platelet activation as assayed by MPC and CD62P expression. Patients were characterized as having either high platelet activity upon admission and positive response to treatment or no detectable platelet activation before or after treatment. This study demonstrates the heterogeneity of platelet activation states in ACS patients undergoing coronary angioplasty. The present work also illustrates the potential use of the MPC parameter, generated on an automated hematology system, to define high risk patients and to monitor the variability of platelet response to anti-platelet therapies.

Abciximab↗
PubMed2006

Warm-up exercise suppresses platelet-eosinophil/neutrophil aggregation and platelet-promoted release of eosinophil/neutrophil oxidant products enhanced by severe exercise in men.

Heterotypic platelet-eosinophil/neutrophil aggregation and subsequent release of eosinophil/neutrophil oxidant products contribute to pathogenesis of conditions such as asthma and inflammatory bowel diseases. This study investigates whether warmup exercise (WUE) affects platelet-eosinophil/neutrophil interaction mediated by high-intensity exercise (HIE). Twenty-three healthy sedentary men performed on three occasions light-intensity exercise (LIE, 40%VO(2 max) for 40 min) and HIE (80%VO(2 max) for 40 min) with and without WUE (40%VO(2 max) for 20 min). Before and immediately after exercise, platelet-eosinophil and platelet-neutrophil aggregation (PEA and PNA), reactive oxygen species production of eosinophils and neutrophils (EROS and NROS) enhanced by platelets, and adhesion molecule expression on platelets, eosinophils, and neutrophils were measured. The results of this study demonstrated that HIE enhanced PEA, PNA, and platelet-induced EROS and NROS, was accompanied by increased expressions of Mac-1 on eosinophils and neutrophils and P-selectin on platelets at 5 dyne/cm(2) of shear stress, 100 microg/ml lipopolysaccharide, and 1 microM N-formylmethionyl- leucyl-phenylalanine treatments, whereas the enhancement of HIE on platelet-eosinophil/neutrophil interaction was suppressed by WUE. Conversely, LIE significantly reduced PEA and PNA, suppressed platelet-induced EROS and NROS, and down-regulated eosinophil/neutrophil Mac-1 and platelet P-selectin expressions under various stimuli and shear flow conditions. Moreover, these effects were more pronounced in platelet interaction with eosinophils than with neutrophils. It is concluded that HIE enhances hetero-aggregation, adhesion molecules expressions, and subsequent oxidative bursts mediated by platelets and eosinophils/neutrophils, this effect diminishes after WUE. However, LIE minimizes the risk of thromboinflammation.

Adult↗
PubMed1985

Platelet function in platelet concentrates and in whole blood.

Platelet function was studied in CPD whole blood stored at 4 degrees C for one and three days and in platelet concentrates stored at room temperature for the same periods of time. Comparisons were made of platelet shape, nucleotide content, beta-thromboglobulin (beta TG) liberated during storage, and platelet aggregation in response to ADP, collagen, sodium arachidonate and ristocetin. It was found that in whole blood the shape of the platelets was less discoid than in platelet concentrates. However, platelet aggregation in response to ADP, collagen, and sodium arachidonate was preserved better in whole blood than in platelet concentrates. Platelet nucleotides were the same in whole blood as in platelet concentrates, but the plasma levels of beta TG were less in whole blood. The results show that as judged by aggregation, beta TG release and nucleotide content, platelets from whole blood were at least as functional as those from platelet concentrates. However, platelets from whole blood had lost their discoid shape, which suggests that they would have a short survival in the circulation.

Adenosine Diphosphate↗
PubMedDate not supplied

[Changes in platelet concentrates from dogs due to storage. I. Platelet count in in vitro function].

The possibility of storage of canine platelet concentrates (PC) was investigated using PC from dogs which were obtained with an automatic cell separator in C4-cell separation sets with low gasdiffusionable Polyvinylchlorid (PVC) storage containers or in C4L-sets developed for storage with high gasdiffusionable Polyolefin (PO) containers, respectively. The storage was carried out for a period of 10 days under permanent agitation at 22 degrees C (C4/22 degrees C, n = 10; C4L/22 degrees C, n = 11) or at 4 degrees C (C4L/4 degrees C, n = 6), respectively. Measurements were done directly after production of the PC, after 6 hours and then daily during the 10-day storage period. In the first part of this paper the results of platelet count (determined automatically with a blood cell differentiation automat and visually), the number of platelet aggregates, the mean platelet volume (MPV) as well as the platelet function with regard to the platelet aggregation induced by collagen or ADP and the resonance-thrombogram (RTG) are presented. The platelet count, measured automatically as well as visually, remained preponderantly constant over the complete storage time in all storage conditions. Dependent on the storage conditions--especially under storage at 22 degrees C--an increase of the number of platelet aggregates and a decrease of MPV was determined. In addition, the loss of platelet function measured by aggregation induced by collagen as well as by ADP showed a significant dependency of storage conditions. The stored platelets lost their ability to aggregate under C4/22 degrees C-conditions after a storage period of 2 days, under C4L/22 degrees C-conditions after 4 days and under C4L/4 degrees C-conditions not before 8 days of storage. Previous resuspending of platelets in fresh plasma delayed the loss of platelet function. Because the loss of platelet function described in the RTG became significant at nearly the same point in time, a storage of canine PC under corresponding conditions can be recommended for upto 2 days (C4/22 degrees C), for 4 days (C4L/22 degrees C) or 8-10 days (C4L/4 degrees C), respectively.

Adenosine Diphosphate↗
PubMed1992

Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. An immunoelectron microscopy study.

The authors used an immunogold labeling procedure to investigate the redistribution of platelet receptors and their ligands on the surface of contact-activated adherent platelets before and after thrombin stimulation. During the initial stage of platelet adhesion, a typical segregation of receptors occurred. Gold particles identifying glycoprotein (GP) Ib (CD42b) and GPIIb-IIIa (CD41a) remained distributed over the entire platelet surface, whereas gold particles identifying GPIa-IIa (CDw 49b) and GPIV (CD36) were found essentially overlying the granulomere; p24 (CD9) was present at the peripheral platelet rim and over the cell body. An increased labeling of GPIIb-IIIa, GPIV and p24 was also observed on pseudopods, with GPIIb-IIIa and GPIV concentrated at the enlarged extremities and at sites of contact between two platelets, whereas GPIb was absent from pseudopods. After thrombin stimulation of adherent platelets, GPIb underwent a relocation to the cell center, in contrast to GPIIb-IIIa which still remained randomly distributed over the cell body. To investigate whether ligand distribution paralleled this receptor segregation, platelet released von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP) were visualized. During the early stages of platelet activation, surface labeling for all three adhesive proteins was minimal and almost undetectable. Occasionally, intragranular Fg and vWF was accessible to gold-coupled antibodies, with vWF exhibiting the typical eccentric alpha-granular localization. At later stages of activation and especially after thrombin stimulation, no surface labeling for vWF was observed, whereas immunogold particles identifying vWF were still present inside enlarged clear vacuoles. In contrast, labeling of Fg and TSP was increased over the granulomere and extended to the cell periphery and the pseudopods, but was absent from the hyalomere, despite the presence of GPIIb-IIIa molecules. Double labeling experiments showed colocalization of Fg and TSP, GPIV and TSP, as well as Fg and GPIIb-IIIa, although no typical coclustering of GPIIb-IIIa and GPIV or GPIIb-IIIa and p24 was apparent. Our results further suggest that 1) on surface activated adherent platelets, not all GPIIb-IIIa molecules become competent to bind Fg, 2) GPIa-IIa is not anchored to the platelet membrane skeleton, and 3) during the early stage of platelet activation, a communication exists between the alpha granules and the platelet surface.

Antigens, CD↗
PubMed1993

Membrane glycoproteins and platelet cytoskeleton in immune complex-induced platelet activation.

To clarify the mechanism of platelet activation by immune complexes and the possible involvement of surface glycoproteins (GPs), we studied platelet activation induced by heat-aggregated IgG (HAG). We examined the effects of monoclonal antibodies (MoAbs) against GPIb, GPIIb/IIIa, and the Fc receptor on resting platelets and on platelets stimulated by HAG. HAG increased the cytosolic ionized calcium concentration ([Ca2+]i) and stimulated protein (P47 and P20) phosphorylation, phosphatidic acid (PA) synthesis, serotonin secretion, and platelet aggregation. IV.3, an anti-Fc gamma RII receptor MoAb, inhibited HAG binding to platelets and all subsequent platelet responses. Like IV.3, MoAbs against GPIIb/IIIa (Tab, 10E5, AP-3) or GPIb (AP-1, 6D1) strongly inhibited platelet activation by HAG. However, while anti-GPIIb/IIIa MoAbs inhibited binding of IV.3 and HAG to platelets, anti-GPIb MoAbs had little effect on platelet binding of IV.3 or HAG. These observations suggest a close topographical and functional association of GPIIb/IIIa with Fc gamma RII in the platelet response to HAG. Cytochalasin B, an inhibitor of actin polymerization, also inhibited platelet activation but not HAG or IV.3 binding. Measurement of the fluorescence of 7-nitrobenz-2-oxa-1,3-(NBD)-phallacidin, a specific marker for filamentous actin (F-actin), showed that both cytochalasin B and AP-1 blocked the increase of F-actin induced by HAG. The common effects of anti-GPIb MoAbs and of cytochalasin B suggest that unlike the activity of GPIIb/IIIa, the ability of anti-GPIb to inhibit the activation of platelets by immune complexes is associated with perturbation of the cytoskeleton.

Antibodies, Monoclonal↗
PubMed1976

Effects of C-reactive protein on platelet function. II. Inhibition by CRP of platelet reactivities stimulated by poly-L-lysine, ADP, epinephrine, and collagen.

It was recently demonstrated that C-reactive protein (CRP)4 inhibits the response of human platelets to heataggregated human gamma-globulin and thrombin and that this inhibition is characterized by a dose-dependent reduction in aggregation, activation of platelet factor 3 (PF3), and release of beta-glucuronidase. In the present experiments, CRP was found also to inhibit the ability of washed human platelets to aggregate in response to poly-L-lysine (PLL); in these experiments, the magnitude of the inhibitory effect was dependent upon the m.w. of PLL used as the stimulating agent, and was more effective with low (15,000 daltons) than with high (400,000 daltons) m.w. polymers. CRP similarly inhibited ADP- and epinephrine-stimulated platelet aggregation in platelet-rich plasma (PRP), and this was characterized by relatively minimal suppression of the primary wave of aggregation. CRP also inhibited the platelet aggregation induced by collagen in PRP, although it had no effect upon the adherence of platelets to collagen. Finally, CRP inhibited the activation of PF3 and the release of serotonin during stimulation of platelets with ADP, and this inhibition was temporally related to the onset of the secondary wave of aggregation. These experiments extend the platelet reactivities inhibited by CRP, show that CRP expresses its inhibitory capacity in platelet-rich plasma as well as upon isolated platelets, raise the possibility that CRP exercises its effects by inhibiting or interfering with the release and/or utilization of endogenous platelet ADP, and support the concept that CRP plays an important role in the control of platelet responsiveness to a variety of stimuli during acute inflammatory reactions.

Adenosine Triphosphate↗
PubMedDate not supplied

Platelet membrane glycoprotein changes during the preparation and storage of platelet concentrates.

Previous studies of platelet membrane glycoproteins during blood bank storage have reported conflicting results. This study assessed two major plasma membrane glycoproteins (GP Ib and GP IIb), an alpha-granule membrane protein (GMP-140), and the concentration of platelet membrane microparticles in cell-free plasma during routine hospital blood bank platelet storage. 125I-monoclonal antibody binding was used to measure membrane glycoproteins on the surface of intact platelets and to measure the concentration of membrane microparticles in cell-free plasma. Platelet concentrates were stored at room temperature in polyolefin bags for 7 days. In this blood bank, two types of rotators are routinely used for platelet concentrate storage: a 2-rpm circular tumbler rotator and a 6-rpm elliptical rotator. Different results were obtained with the rotators. With the tumbler rotator, there was no loss of platelets and antibody binding to GP Ib remained normal. With the elliptical rotator, one third of platelets were lost into clumps during storage, and a 50 percent decrease of antibody binding to GP Ib occurred in the remaining single platelets. There was no loss of antibody binding to GP IIb with either rotator. Antibody binding to GMP-140 increased equally in both rotators indicating that the remaining single platelets had secreted about 16 percent of their alpha-granule contents. The plasma concentration of platelet membrane microparticles was greater in the bags stored in the elliptical rotator. These results indicate that it is possible to maintain the normal concentration of platelet membrane glycoproteins Ib and IIb during 7 days of room-temperature blood bank storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed2002

Platelet adhesion onto a polystyrene surface under static conditions: role of specific platelet receptors and effect of divalent cations.

An experimental model was used to elucidate the basic mechanisms involved in the interaction of platelets with an artificial surface. The role of divalent cations and the involvement of specific platelet membrane receptors were evaluated. Isolated platelets were allowed to interact with a polystyrene surface for 20 min in the presence of divalent cations (Ca2+, Mg2+ or Zn2+), a chelating agent (ethylenediaminetetraacetic, EDTA), and specific antibodies to the main platelet receptors, glycoproteins (GP) Ib and IIb-IIIa. The degree of platelet interaction was evaluated using light and electron microscopy. Morphometric analysis was performed to follow up the progression of platelet shape changes after surface activation. Neither Ca2+ nor Mg2+ influenced the number of adherent platelets or the degree of spreading on the polymer. Only Zn2+ induced a statistically significant increase in the rate of platelet adhesion (P<0.01) with higher proportion of fully spread platelets (P<0.01). Chelation of internal pools of divalent cations did not modify the rates of platelet adhesion but prevented platelet spreading. Presence of monoclonal antibodies to GPIb and GP IIb-IIIa did not result in significant differences in the studied parameters. These results suggest that platelet adhesion onto artificial surfaces, in the absence of flow and plasma proteins, is more dependent on cellular motility, where Zn2+ could play an important role, and less dependent on major receptorial mechanisms.

Antibodies, Monoclonal↗
PubMed1998

Characterization of adhesive and aggregating functions of pig platelets: comparative studies with human platelets and differential effects of calcium chelation.

We have characterized functional responses of pig platelets in citrate-anticoagulated blood and compared results with those of human platelets. Platelet aggregation was induced with known activating agents using citrated platelet-rich plasma. Adhesive and cohesive functions of platelets were evaluated using a perfusion flow system with whole anticoagulated blood (10 min, 800/s). To test the differential sensitivity to free calcium levels, two citrate concentrations (19 mM [standard] vs 13 mM) were used as anticoagulants. The ability of platelets to produce thromboxane A2 was also quantified, using radioimmunoassay. In the presence of 19 mM citrate concentration, pig platelets responded poorly to ADP and collagen, and did not respond to arachidonic acid and U46619. Pig platelets adhered well onto subendothelium, but failed to form aggregates on previously spreaded platelets. At 13 mM citrate concentration, the aggregating responses of pig platelets improved, but some of the aggregation patterns were still reversible. The lower citrate concentration had a dramatic impact on perfusion studies, where the formation of platelet aggregates was restored up to levels found in humans. Thromboxane levels in pig serum were only 20 to 30% of that found in humans. So, pig platelets possess functional properties that clearly differ from human platelets: they are more sensitive to the calcium chelating effects of citrate. Arachidonic acid metabolism and thromboxane amplification of platelet responses seem less preponderant in the pig species.

Journal Article↗
PubMed2000

Two different types of nonthrombogenic surfaces: PEG suppresses platelet adhesion ATP-independently but HEMA-St block copolymer requires ATP consumption of platelets to prevent adhesion.

Poly(ethylene glycol) (PEG) and a hydrophobic-hydrophilic microdomain structured block copolymer comprising poly(2-hydroxyethyl methacrylate) and polystyrene (HEMA-St) have been reported to show good blood compatibility owing to inhibition of platelet activation. By using a computer-assisted novel technique to analyze platelet behavior on the surfaces, we found two different mechanisms to prevent platelet adhesion. Platelets were prevented from adhesion and spreading on the microdomain surface and retained cell movement for a long time. The platelet movement velocity was not significantly different between PEG-grafted surfaces and HEMA-St block copolymer-cast surfaces. However, platelet motion was qualitatively different. Platelets on HEMA-St block copolymer-cast surfaces moved with rolling, spinning, and vibrating, whereas platelet movement was limited to oscillatory vibration on PEG-grafted surfaces. When platelets were treated with NaN(3), an adenosine triphosphate (ATP) synthesis inhibitor, before contacting the surfaces, platelets movement velocity was decreased only on HEMA-St block copolymer-cast surfaces. Such an inhibitory effect was hardly observed with platelets on PEG-grafted surfaces. We propose two different mechanisms to prevent platelet adhesion onto surfaces. One is ATP-independent as observed with PEG, and the other is ATP-dependent for HEMA-St block copolymer, where platelets consume ATP to prevent adhesion.

Adenosine Triphosphate↗
PubMed1994

Changes in platelet membrane glycoproteins and platelet-leukocyte interaction during hemodialysis.

Platelet aggregation and interaction with other vascular cells play a key role in hemostatic events during hemodialysis. We studied seven patients with end-stage renal failure on long-term hemodialysis treatment. Flow-cytometric techniques and platelet-specific monoclonal antibodies were used to measure the platelet surface expression of glycoproteins-fibrinogen receptor on glycoprotein IIb-IIIa (GP IIb-IIIa; CD41) and alpha-granule membrane protein (GMP-140; CD62). In addition, adhesion of platelets or platelet microparticles with leukocytes was evaluated by appearance of the platelet-specific antigen (GP IIb-IIIa) on leukocytes. Blood samples were taken before the start of dialysis and 15, 60, and 240 min thereafter. There was a significant increase in fibrinogen receptor activation on circulating platelets after 15 min of dialysis treatment (P < 0.001) and enhanced degranulation of GMP-140 (P < 0.05). In parallel, the interaction of platelets with neutrophils and monocytes also increased with the duration of dialysis and was maximal after 15 min (P < 0.001). We conclude that the platelet fibrinogen receptor on GP IIb-IIIa in circulating platelets is activated during hemodialysis and is associated with increased adhesion of platelets or platelet microparticles with circulating leukocytes. Thus, the phenomenon described here of platelet-leukocyte interaction could be pathophysiologically important for the development of dialysis-associated leukopenia.

Adult↗
PubMed1986

Primary dysfunction in aggregation and secretion of SHRSP platelets: not secondary to the circulation of "exhausted" platelets.

The thrombin-induced secretion of [14C]-serotonin and adenine nucleotides from stroke-prone spontaneously hypertensive rats (SHRSP) platelets was markedly reduced with the development of hypertension accompanying hypo-aggregability compared with that from age-matched Wistar Kyoto rats (WKY) platelets. Calcium Ionophore A23187-induced secretion and aggregation were also attenuated in SHRSP platelets. Additionally, an enhancement of platelet secretion as well as aggregation by extracellular Ca2+ was less in SHRSP platelets than in WKY platelets. The platelet contents of adenine nucleotides and serotonin were not different between SHRSP and WKY at 5-16 weeks of age whereas they became significantly lower in SHRSP beginning at 22 weeks. The serotonin content in SHRSP platelets at 36 weeks of age was only 55% of that in WKY platelets. It is suggested that the reduced platelet aggregation and secretion observed in SHRSP platelets at ages lower than approximately 20 weeks are not secondary phenomena to the circulation of degranulated platelets, but the primary defect of SHRSP platelets appears to be an impaired function of Ca2+.

Adenine Nucleotides↗