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PubMed1993

Enhancement of cathepsin G-induced platelet activation by leukocyte elastase: consequence for the neutrophil-mediated platelet activation.

We have focused our interest on the platelet-activating properties of two polymorphonuclear neutrophil (PMN)-derived proteinases, namely elastase (HLE) and cathepsin G (Cat.G). First of all, we observed that whereas HLE was unable to trigger platelet activation by itself, it enhanced platelet activation induced by Cat.G when both proteinases were added simultaneously. It has been recently described that, upon stimulation, PMN released Cat.G, which in turn activated surrounding platelets. Thus, we looked for a combined effect of Cat.G and HLE during this cell-to-cell interaction. When PMN (5 x 10(6)/mL) were stimulated by 0.5 mumol/L N-formyl-Met-Leu-Phe, they released 237.9 +/- 49.1 nmol/L Cat.G and 381.7 +/- 28.0 nmol/L HLE. Such a concentration of purified Cat.G (240 nmol/L) induced only a moderate platelet activation when added to a PMN-platelet mixture. However, when Cat.G (240 nmol/L) and HLE (380 nmol/L) were added together, the resulting platelet activation was strictly comparable to that corresponding to the addition of N-formyl-Met-Leu-Phe (P > .05) in terms of aggregation, dense and alpha granule secretion, and thromboxane B2 production. In fact, Elafin, a specific HLE inhibitor, when added to the PMN-platelet cooperation system triggered by N-formyl-Met-Leu-Phe, prevented platelet activation within the same range of concentrations as for inhibition of HLE activity. In conclusion, we now show that not only Cat.G, but also HLE is involved in the PMN-mediated platelet activation.

Amino Acid Sequence↗

PubMed1996

[Improved method of staining RNA in platelets for the evaluation of platelet production in thrombocytopenic patients].

Measurement of RNA stained platelets was proven to be an easy and useful laboratory test to evaluate the state of platelet production in the bone marrow. As the normal value of RNA stained platelet with thiazole orange(TO) in the original method was low, the values of TO-stained platelets in the cases with platelet hypoproduction were within the normal range, but ideally, they should be below the normal range. We modified the original method 1) by using sodium citrate as the anticoagulant instead of EDTA, and 2) by keeping the TO-stained preparation at 4 degrees C until the fluorescence was measured. The normal value of TO-stained platelets was elevated to 22.5 +/- 3.3% (n = 40, M +/- 1SD) or 54 +/- 10 x 10(9)/1. Twenty-seven out of 40 thrombocytopenic case with ITP showed an elevated percentage of TO-stained platelets, 11 cases showed a normal and only 2 cases showed a percentage lower than normal. By contrast, 9 out of 12 cases with platelet hypoproduction showed a lower percentage of TO-stained platelets and no cases showed a value higher than normal. The sensitivity and specificity of this modified RNA staining method for distinguishing thrombocytopenic cases with platelet hyperdestruction from that with hypoproduction were 96% and 75%, respectively.

Adult↗

PubMed1998

Vesiculation and changes in fluidity and lipid composition of platelet membranes after storage of sheep platelets in plasma or Seto solution.

To relate the improvement of platelet storage in synthetic media with possible structural changes, we conducted serial studies on the membranes of platelets and microparticles shed during platelet storage for up to 5 days at 4 degrees C either in plasma or in Seto solution. Spontaneous microparticle formation proceeded linearly for up to 2 days in both storage media, although the processes seemed to be different because microparticles from Seto solution had a higher lipid/protein ratio than those released in plasma. Microparticles were heterogeneous structures showing beta-N-acetylhexosaminidase, glucose-6-phosphatase and succinate dehydrogenase activities. After 2-5 days of storage, microparticles contained 60% of total cellular acetylcholinesterase (AChE), were doubly enriched in cholesterol. and showed identical phospholipid profiles but with a decrease in the lipid unsaturation index with respect to fresh platelets. Fluorescence anisotropy studies pointed to a remarkable increase in the deep lipid core fluidity of microparticles during storage of platelets in plasma. With respect to platelets, only those stored in plasma showed significant changes in lipid contents, with a 3-fold decrease in the phospholipid to protein ratio, a decrease in phosphatidylethanolamine (PE) levels and a parallel increase in phosphatidylcholine (PC) percentages in their phospholipid profile, together with a significant reduction in the lipid unsaturation index after 1 day of storage. The fluidity of the negatively charged surface of the platelet membranes decreased in platelets stored for 5 days in both media, whereas the fluidity of the membrane deep core was only increased in platelets stored in plasma. These findings suggest that Seto solution permits better storage of platelets for 5 days than plasma and support the notion that lipid peroxidation could play an important role in the structural changes observed.

Animals↗

PubMed1995

Conversion from chronic to acute coronary heart disease syndromes. Role of platelets and platelet products.

Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium.

Animals↗

PubMed1998

Effect of recombinant human erythropoietin treatment on circulating reticulated platelets in uremic patients: association with early improvement in platelet function.

Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg(-1)i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5'-diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin-induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets.

Adenosine Diphosphate↗

PubMed1990

Effects of calcium channel-blocking agents on platelet-osteogenic sarcoma interaction: platelet aggregation and electron microscopic findings.

A variety of tumors stimulate platelet activation. Because platelet activation may, in part, require calcium channel mobilization, we evaluated whether calcium channel blocking agents inhibit osteogenic sarcoma induced platelet aggregation. Platelet rich plasma (PRP) from normal subjects was incubated with one of four calcium channel-blocking agents: nifedipine, diltiazem, verapamil, or amlodopine, all 0-25 micrograms/ml, or diluent. Osteogenic sarcoma cells (2 or 4 x 10(6)/ml) were then added. Platelet aggregation was monitored by light transmission through PRP, and residual PRP was processed for electron microscopy. MG63 cells caused aggregation of PRP in most subjects (mean, 36 +/- 3%). Calcium channel-blocking agents (nifedipine greater than diltiazem greater than amlodopine greater than verapamil) caused partial inhibition of osteogenic sarcoma-induced platelet aggregation, at high concentrations only. Electron microscopy showed platelets aggregating to each other and to tumor cell membranes within 1-5 minutes. Changes in pattern of platelet clumping around tumor cells occurred when PRP was incubated with high concentration of diltiazem (50 micrograms). This study shows that calcium channel-blocking agents inhibit osteogenic sarcoma-induced platelet aggregation when used in high doses.

Blood Platelets↗

PubMed1999

Characterization of liposomes carrying von Willebrand factor-binding domain of platelet glycoprotein Ibalpha: a potential substitute for platelet transfusion.

Platelet glycoprotein (GP) Ib/IX/V complex is a receptor for von Willebrand factor (vWf), which plays a crucial role in primary hemostasis by mediating platelet adhesion to injured blood vessels. We have expressed in CHO cells a fragment of GPIba that retained a vWf-binding function. The recombinant fragment (rGPIba) was incorporated into liposomes and evaluated their functions in vitro. rGPIba on the liposome surface was detectable by flow cytometric analysis. Addition of vWf and ristocetin caused specific agglutination of rGPIbalpha-liposomes, as evaluated by an aggregometer or a fluorescent microscopy. When ristocetin was added to platelet-rich plasma (PRP) pre-mixed with rhodamine-labeled rGPIbalpha-liposomes, platelets aggregated and rhodamine-fluorescence was strongly positive in the platelet thrombi, suggesting that heterologous aggregation (attachment of liposomes to platelets) occurred. Platelet aggregation in PRP at low platelet concentration (20-80 x 10(6)/ml) was enhanced by rGPIbalpha-liposomes in a dose-dependent manner. Thus, rGPIbalpha-liposomes may accumulate on vWf-exposed subendothelial tissues and enhance platelet function in vivo, supporting hemostasis in thrombocytopenic individuals.

Animals↗

PubMed1992

Stabilization of standard platelet concentrates and minimization of the platelet storage lesion by a prostacyclin analogue.

Platelet concentrates were pretreated with a stable synthetic prostacyclin analogue (Iloprost) at two different concentrations before the second centrifugation step (pelleting step) of preparation. This resulted in loss of platelet sensitivity to aggregating agents. To mimic the situation after transfusion and to assess the reversibility of platelet inhibition, platelets were washed during and after storage and resuspended in fresh-frozen autologous plasma. The Iloprost-treated and washed platelets exhibited an increased sensitivity to the aggregating agents, compared with the control platelets (p less than 0.01). Post-storage recovery of the synergistic aggregation was more than 80% of prestorage aggregation. Beta-thromboglobulin (beta TG) release and thromboxane B2 (TXB2) formation were significantly inhibited in Iloprost-treated platelets (p less than 0.01). After the second centrifugation step, beta TG release was 0.7% +/- 0.3%, compared with 2.7% +/- 0.9% for the controls. TXB2 was 99 +/- 91 pg/ml, compared with 495 +/- 356 pg/ml for the controls. Platelet morphology and ultrastructure were well preserved during 5-day storage. In addition, Iloprost exerted a cytoprotective effect, as evidenced by the significant reduction in lactate dehydrogenase leakage. Post-storage LDH was 378 +/- 159 and 415 +/- 239 U/l respectively by the two Iloprost concentrations, compared with 1180 +/- 937 U/l for the control platelets. The inhibitory and cytoprotective effects of Iloprost were sustained throughout storage, in contrast to the effect of PGE1 (Prostin) which was limited to the early phase of storage.

Alprostadil↗

PubMed1991

Protein kinase C is not involved in the desensitization of platelet activating factor receptor in rabbit platelets.

Rabbit platelets pretreated with platelet activating factor (PAF) became refractory to further stimulation by PAF. The effect was specific for PAF. In this study, the alteration in the specific agonist binding to PAF receptor in platelets following desensitization was investigated. As revealed by the Scatchard analysis of radioligand binding data, the affinity for specific PAF binding to desensitized platelet membranes was substantially lowered as compared with that to control platelet membranes. Guanine nucleotide triphosphate, which was shown to decrease the affinity of specific PAF binding to platelet membranes, had less effect on the PAF binding affinity to the desensitized preparation. In platelets pretreated with phorbol 12-myristate-13-acetate, the binding affinity of PAF receptor remained unaltered. Pretreatment of platelets with 1-(5-isoquinolinesulphonyl)-2-methylpiperazine, a protein kinase C inhibitor, or neomycin, an inhibitor of the polyphosphoinositide breakdown, failed to prevent the reduction of specific PAF binding affinity following subsequent exposure to PAF. These results suggest that the agonist-induced desensitization of PAF receptor in rabbit platelets is independent of activation of protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1992

Dual effects of oleic acid on Ca2+ mobilization and protein phosphorylation in human platelets in presence or absence of platelet activating factor.

This laboratory demonstrated earlier that oleic acid inhibited platelet activating factor (PAF)-induced aggregation and serotonin release of rabbit platelets (M. Miwa, C. Hill, R. Kumar, J. Sugatani, M. S. Olson, and D. J. Hanahan, 1987, J. Biol. Chem. 262, 527-530). More recently, we reported that oleic acid caused a decrease in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2), but did not affect the level of inositol-1,4,5-trisphosphate (IP3), in rabbit platelets (D. Nunez, J. Randon, C. Gandhi, A. Siafaka-Kapadai, M. S. Olson, and D. J. Hanahan, 1990, J. Biol. Chem. 265, 18330-18838). These results suggested that oleic acid did not stimulate phospholipase C. In contrast, PAF induced a decrease in PIP2 and an increase in PIP level and IP3. These effects were shown to be attenuated by oleic acid. In this current study, our experiments show that (a) oleic acid blocked PAF-induced rise in intracellular [Ca2+] (to provide a mechanism in agreement with our previous experiments which showed that oleic acid inhibited PAF-induced IP3 rise in platelets) and (b) oleic acid itself induced a gradual rise in [Ca2+]i, which would provide a mechanism for oleic acid-induced aggregation despite the fact that oleic acid did not cause the production of IP3 (Nunez et al., 1990). Oleic acid, in a dose-dependent manner, was shown to inhibit PAF-induced Ca2+ mobilization from intra- and extracellular sources. The inhibition was closely related to the suppressive effect of oleic acid on PAF-induced aggregation. Furthermore, oleic acid inhibited the PAF-stimulated phosphorylation of the 20- and 40-kDa proteins. At concentrations above 20 microM, oleic acid itself could induce platelet aggregation and Ca2+ mobilization, but the time sequence of these two responses in human platelets was significantly different from those obtained with PAF. Oleic acid alone, at 20 microM, caused a 1.4-fold increase in the cAMP level in platelets which was followed by a decline to a basal value at higher concentrations of this fatty acid. It seemed clear that elevation of adenylate cyclase activity was not associated with free fatty acid inhibition of platelet activation. Interestingly, both PAF and oleic acid added separately to human platelets induced protein-tyrosine phosphorylation, but oleic acid did not cause any inhibition of PAF-induced protein-tyrosine phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Platelets↗

PubMed1983

Studies on the stimulation of human blood platelets by semi-synthetic platelet-activating factor.

"Saturated" and "unsaturated" platelet-activating factor (PAF) obtained from ratfish liver oil were proved to exert potent stimulation on human blood platelets. Using 0.025 to 1.0 mumol/1 PAF a dose-dependent platelet aggregation in platelet-rich plasma was observed. During PAF-induced irreversible aggregation a 9 to 40% release of platelet bound serotonin occurred. The specific effect of PAF, however, seems to be limited to induce reversible aggregation since second wave of aggregation and serotonin release were suppressed by a combination of acetylsalicylic acid and an ADP scavenging system. Incubation of PAF for 30 min in plasma resulted in a 90% loss of its platelet aggregating power. Subthreshold concentrations of PAF enhanced the platelet aggregation triggered by suboptimal concentrations of ADP, epinephrine, or collagen. Vice versa non-aggregating concentrations of ADP, epinephrine, collagen, Ca-ionophore A 23,187, or arachidonic acid amplified PAF-induced platelet aggregation. The synergistic effect of PAF and other stimuli of blood platelet activation can be partly interpreted as a stimulating effect of PAF on the metabolization of arachidonic acid.

Adenosine Diphosphate↗

PubMed1982

Platelet activating factor (PAF) causes human platelet aggregation through the mechanism of membrane modulation.

Recent investigations have shown that human and canine platelets possess a new pathway for securing irreversible platelet aggregation independent of ADP secretion and prostaglandin synthesis. Platelet activating factor (PAF) is a potent aggregating agent for rabbit platelets and is also reputed to stimulate the cells by a completely independent pathway. Since the newly recognized mechanism in human and dog cells, termed membrane modulation, might be mediated by PAF, we evaluated the influence of this agent on human cells. Results of that study demonstrated that PAF did not activate platelets through an independent pathway and was not involved in the mechanism of membrane modulation. In the present investigation we have examined the possibility that PAF might act on human platelets through the mechanism of membrane modulation. Human platelets were made refractory to amounts of PAF routinely causing irreversible aggregation by prolonged incubation of C-PRP at 37 degrees C, by exposure to PGI2 or aspirin, or by aggregation-disaggregation of control or aspirin treated cells. Epinephrine at concentrations which did not cause aggregation turned on the mechanism of membrane modulation in refractory platelets and restored their sensitivity to PAF. Thus, PAF does not appear to activate human platelets through a unique, independent pathway. Rather, it usually causes irreversible aggregation of human cells through the mechanisms of ADP secretion and thromboxane synthesis or, as shown in this study, can be dependent on membrane modulation.

Adenosine Diphosphate↗

PubMed1995

Platelet activation and platelet lipid composition in pulmonary cancer.

In order to investigate the possible mechanisms underlying platelet functional changes in patients affected by neoplasms, platelet lipid composition, plasma beta-thromboglobulin (Beta-TG) and serum thromboxane B2 (TXB2) were investigated in 16 male patients affected by pulmonary carcinoma and in 16 comparable control subjects. In patients high levels of plasma Beta-TG (67 +/- 9 versus controls 14 +/- 4 ng/ml, p < 0.001) and serum TXB2 (434 +/- 56 versus 223 +/- 48 ng/ml, p < 0.001) were observed. Also platelet lipid composition was found altered in patients with respect to controls (lower percent levels in n-3 fatty acids and in linoleic acid esterified in the main platelet phospholipid fractions: at least p < 0.05). These results indicate that in vivo platelet activation is detectable in neoplastic patients and it is associated with alterations in platelet lipid composition. In the light of the important role played by membrane lipids in platelet functions related to thrombosis and haemostasis we conclude that platelet lipid changes could cooperate in platelet activation and increased thrombotic risk so frequently observed in neoplastic disease.

Adult↗

PubMed2004

Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome.

OBJECTIVES: We sought to characterize the effects of clopidogrel on the activation of circulating platelets, the activation and aggregation of ex vivo platelets, and the interactions with leukocytes in patients with a non-ST-segment elevation in acute coronary syndromes (ACS). BACKGROUND: The significant benefits of clopidogrel in cardiovascular trials suggest that blockage of the P2Y(12) receptor may be associated with important biologic consequences. METHODS: Blood samples obtained from 23 ACS patients before and 24 h after a loading dose of clopidogrel (300 mg) were analyzed by whole-blood flow cytometry, light transmission aggregometry in platelet-rich plasma, and plasma enzyme-linked immunoassays. A thrombin receptor agonist peptide (TRAP) and adenosine diphosphate (ADP) were used as agonists. Normal individuals pretreated with aspirin served as controls. RESULTS: Clopidogrel attenuated platelet aggregation to both ADP (10 micromol/l) and TRAP (10 micromol/l) by 22% and P-selectin expression by 16% and 25%, respectively. The drug decreased the excess platelet-monocyte and platelet-neutrophil conjugates found in the blood of ACS patients (p < 0.01) and prevented their formation ex vivo with agonist stimulation. Plasma levels of soluble CD40L were reduced by 27% (p < 0.001) and of soluble P-selectin by 15% (p < 0.001). CONCLUSIONS: Clopidogrel attenuates the agonist effects of ADP and TRAP on platelet secretion, aggregation, and formation of platelet-monocyte and platelet-neutrophil conjugates in patients with ACS. These effects may all contribute to the clinical benefits of the drug in these syndromes.

Adenosine Diphosphate↗

PubMed1997

Platelet alpha granule deficiency associated with decreased P-selectin and selective impairment of thrombin-induced activation in a new patient with gray platelet syndrome (alpha-storage pool deficiency).

We report studies on a new patient with gray platelet syndrome (GPS, alpha-storage pool deficiency). Her lifelong bleeding history is associated with platelet abnormalities characteristic of GPS including mild to moderate thrombocytopenia, a population of abnormally large platelets, and specific deficiencies of alpha-granule constituents and morphologically typical alpha-granules. Platelet function studies showed normal aggregation responses to adenosine diphosphate, epinephrine, collagen, arachidonate, and ristocetin but impaired activation responses to thrombin and a thrombin receptor-activating peptide (T1 peptide). These impaired responses included T1 peptide-induced aggregation, thrombin-induced adenine nucleotide secretion, and thrombin-induced (Ca2+)i increases. The impairment of the thrombin-induced (Ca2+)i increase was observed as a substantially slower initial rise in (Ca2+)i levels and a smaller maximum (Ca2+)i increase compared with the responses obtained in normal platelets and are thus similar to those reported previously in another patients with GPS. Flow cytometric measurements of the binding of two distinct monoclonal antibodies against the functional thrombin receptor indicated the presence of a normal number of receptors and normal receptor cleavage by thrombin in the GPS platelets, providing additional support for the hypothesis presented in previous studies that the thrombin activation defect in GPS platelets occurs subsequent to the interaction of thrombin with its receptor. The alpha-granule deficiency in this patient was associated with an approximately 50% decrease in the content and surface expression of the alpha-granule membrane-specific protein P-selectin in contrast to a previous report of normal amounts of P-selectin in the platelets of two related patients with GPS. This finding raises the possibility that the alpha-granule deficiency in GPS may be expressed in different phenotypes characterized by differences in the amount or constitution of residual alpha-granule membranes present in GPS platelets.

Adenosine↗

PubMed2000

Responses to aggregating agents after cleavage of GPIb of human platelets by the O-sialoglycoprotein endoprotease from Pasteurella haemolytica- potential surrogates for Bernard-Soulier platelets?

Most proteolytic enzymes that cleave glycoprotein lb (GPlb) also cleave other glycoproteins or receptors on the surface of platelets. We have used an O-sialoglycoprotein endoprotease from Pasteurella haemolytica that selectively cleaves the heavily O-glycosylated GPlb, but does not cleave N-linked glycoproteins or unglycosylated proteins. Isolated, [14C]serotonin-labeled platelets in Tyrode-albumin solution were incubated with 10 microg/mL endoprotease for 60 minutes at 37 degrees C. These platelets did not release [14C]serotonin, had no detectable GPIb, and were unresponsive to ristocetin/von Willebrand factor. Compared with control platelets, aggregation and release of [14C]serotonin by the endoprotease-pretreated platelets were inhibited in response to low concentrations of thrombin, SFLLRN (the PAR-1-activating peptide), collagen, and U46619 (a thromboxane A(2) mimetic); aggregates were smaller in size. The presence of fibrinogen overcame the inhibition of responses induced by SFLLRN, collagen, and U46619. With fibrinogen, primary ADP-induced aggregation was scarcely affected by pretreatment with the endoprotease. Thus, the PAR-1 receptor for thrombin, and receptors for collagen, thromboxane A(2), fibrinogen (GPIIb/IIIa), and ADP appear to function normally on the endoprotease-pretreated platelets. Since only GPIb is cleaved by the endoprotease, these platelets seem to provide potential surrogates for Bernard-Soulier syndrome platelets for further studies of platelet functions in this condition.

Agglutination↗

PubMed2001

Clinical utility of the platelet function analyzer (PFA-100) for the assessment of the platelet status in patients with congestive heart failure (EPCOT trial).

BACKGROUND: Data from small studies have shown the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of platelet function analyzer (PFA-100) in the CHF population. METHODS: Blood samples were obtained for measurement of adenosine diphosphate (ADP)/collagen and epinephrine/collagen shear-induced closure time (CT), whole blood aggregation, platelet contractile force, activity of glycoprotein (GP) IIb/IIIa, and P-selectin receptors in 100 consecutive outpatients with CHF. RESULTS: Substantial interindividual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were divided by the incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Aspirin use did not affect instrument readings as well. CT correlates well with whole blood aggregometry (r(2)=.587) and less with GP IIb/IIIa activity (r(2)=.326). No correlation has been observed for the CT with the platelet-bound P-selectin (r(2)=.041) and platelet contractile force measures (r(2)=.028). CONCLUSIONS: PFA-100 is indeed capable to serve as a platelet analyzer and may be successfully used as a screening device. However, patients with heart failure enrolled in the EPCOT trial exhibited a marginal, sometimes oppositely directed changes in the platelet function, challenging the diagnostic utility of PFA-100 to serve as a useful tool for the identification of platelet abnormalities, predicting clinical outcomes, or for the monitoring of antiplatelet strategies in this population.

Adenosine Diphosphate↗

PubMed2000

Platelets and the injured vessel wall-- "rolling into action": focus on glycoprotein Ib/V/IX and the platelet cytoskeleton.

Blood platelets play a key role in maintaining the integrity of the vascular system through their ability to arrest bleeding (haemostasis) and promote repair of injured blood vessels. Considerable progress has been made in the last few years in our understanding of the adhesion mechanisms utilized by platelets to adhere to sites of vascular injury. Studies have helped define the precise role of von Willebrand factor (vWf), and its platelet receptor, glycoprotein (GP) Ib/V/IX, in initiating platelet-vessel wall and platelet-platelet adhesion contacts. In addition to its adhesive role, recent studies have highlighted the importance of GPIb/V/IX in regulating the cytoskeleton of platelets. GPIb/V/IX not only maintains the normal cytoskeletal architecture of resting platelets but also induces cytoskeletal reorganization following engagement of vWf. Somewhat surprisingly, the physical link between GPIb/V/IX and the membrane skeleton does not appear necessary for GPIb/V/IX-induced cytoskeletal reorganization. In contrast, this linkage appears critical for GPIb/V/IX to maintain cell adhesion under high shear and also for the ability of the cytoskeleton to exert negative regulatory effects on the GPIb-vWf interaction. Thus a complex functional relationship appears to exist between GPIb/V/IX and the membrane skeleton that goes well beyond preserving the normal cytoskeletal architecture of resting platelets.

Blood Platelets↗