Accumulation of Macromolecular Particles in the Reticuloendothelial System (RES) Mediated by Platelet Aggregation and Disaggregation

1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Reticuloendothelial System ◽  
Caproic Acid ◽  
Carbon Particles ◽  
Carbon Clearance ◽  
Aggregation And Disaggregation ◽  
Platelet Aggregates

SummaryCarbon particles cause platelet aggregation in vitro and in vivo. Prior studies established that substances which modify thrombocyte aggregation also influence the rate at which carbon is cleared from the blood.This study was performed in order to elucidate the mechanism by which the carbon-platelet aggregates specifically accumulate in the RES.Activation of fibrinolysis by urokinase or streptokinase reduced the carbon clearance rate, probably due to generated fibrinogen degradation products (FDP). Isolated FDP decreased the carbon clearance and caused disaggregation of platelets and particles in vitro. Inhibition of fibrinolysis by epsilon-amino-caproic acid (EACA), initially accelerated the disappearance of carbon and caused particle accumulation outside the RES, predominantly in the lungs. It is supposed that platelet aggregation and locally activated fibrinolysis act together in the clearance of particles. In the normal situation the RES with its well known low fibrinolytic activity, becomes the receptor of the particles.

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

The Filtragometer: A New Device for Measuring Platelet Aggregation in Venous Blood of Man

1975 ◽  
Vol 34 (02) ◽  
pp. 531-544 ◽  
Author(s):  
G Hornstra ◽  
F ten Hoor
Keyword(s):  
Platelet Aggregation ◽  
Pressure Difference ◽  
Venous Blood ◽  
New Device ◽  
Platelet Aggregates ◽  
Spontaneous Platelet Aggregation ◽  
Short Time ◽  
Forearm Vein

SummaryA new device for the direct assessment of spontaneous platelet aggregation in human venous blood is described: the Filtragometer. The principle of the method is based on measurement of the pressure difference across a filter with pores of 20 μπι diameter through which blood from a forearm vein is drawn. Platelet aggregates, obstructing the filter, cause a change in the pressure difference which is proportional to the degree of platelet aggregation. The measurement takes only a short time and a small amount (5-10 ml) of blood.Platelet aggregation as measured with the Filtragometer depends on the type of anticoagulant used. The Filtragometer response decreases on inhibition of platelet stickiness in vitro by prostaglandin E1 and in vivo by aspirin ingestion. Moreover it appeared to be higher in a group with a high thrombosis tendency than in a group less susceptible to fatal arterial thrombosis.The Filtragometer seems especially useful in monitoring the results of diet and/or drug therapy.

Influence of Fibrinogen Split Products on Platelets

1967 ◽  
Vol 17 (01/02) ◽  
pp. 078-098 ◽  
Author(s):  
M. I Barnhart ◽  
D. C Cress ◽  
R. L Henry ◽  
J. M Riddle
Keyword(s):  
Platelet Aggregation ◽  
Plasma Concentration ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Platelet Response ◽  
Transient Nature ◽  
Platelet Morphology ◽  
Platelet Aggregates

SummaryBreakdown products of fibrinogen and fibrin can play a role in hemostasis and also may be of consequence in thrombosis. β2 fibrinogen derivative D is an electropositive terminal proteolysis product of fibrinolysis which has the ability to aggregate platelets. The normal plasma concentration of such nonclottable fibrinogen relatives is 0.2 mg/ml. During fibrinolysis this concentration may reach 5 mg/ml plasma. Addition of β 2 fibrinogen D (raising the plasma concentration 0.1 to 5 mg/ml) either in vivo or in vitro induced platelet aggregations. Moreover, alterations in platelet morphology occurred which were obvious by electron microscopy.Platelet depletion was a consistent response to the infusion of purified β2 fibrinogen D (8 to 55 mg/kg body weight) into dogs. Circulating platelets decreased as much as 85% but were only temporarily aggregated and reappeared in the circulation within 1 to 5 hrs. Small platelet aggregates circulated while large aggregates were trapped in the microcirculation. Thrombin was not responsible for the platelet aggregations as neither prothrombin nor clottable fibrinogen were changed significantly. The transient nature and morphological features of the platelet response according to microscopic criteria were prominent during and after infusion of β2 fibrinogen D.In vitro studies included 3 systems; washed platelets, platelet rich plasma and whole blood. Positive results were obtained with all, but platelets in whole blood were most responsive. The magnitude of platelet aggregation and morphology correlated with the concentration of β2 fibrinogen D. Platelet aggregation induced by ADP (10~5 mg/ml) was compared with that induced by β2 fibrinogen D (0.09 to 0.72 mg/ml). With either reagent aggregates were of dendritic forms. Combination of the 2 reagents was additive but did not further change the morphology. Additional factors seem necessary for development of viscous metamorphosis.

scholarly journals Intratumoral platelet aggregate formation in a murine preclinical glioma model depends on podoplanin expression on tumor cells

2019 ◽  
Vol 3 (7) ◽  
pp. 1092-1102 ◽  
Author(s):  
Barbara Costa ◽  
Tanja Eisemann ◽  
Jens Strelau ◽  
Ingrid Spaan ◽  
Andrey Korshunov ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Tumor Cells ◽  
Cell Types ◽  
Platelet Receptor ◽  
Increased Risk ◽  
Platelet Aggregates ◽  
Glioma Model ◽  
Novel Strategy

Abstract Binding of the sialomucin-like transmembrane glycoprotein podoplanin (PDPN) to the platelet receptor C-type lectin-like receptor 2 induces platelet activation and aggregation. In human high-grade gliomas, PDPN is highly expressed both in tumor cells and in tumor-associated astrocytes. In glioma patients, high expression of PDPN is associated with worse prognosis and has been shown to correlate with intratumoral platelet aggregation and an increased risk of venous thromboembolism (VTE). To functionally assess the role of PDPN in platelet aggregation in vivo, we established a syngeneic orthotopic murine glioma model in C57/Bl6 mice, based on transplantation of p53- and Pten-deficient neural stem cells. This model is characterized by the presence of intratumoral platelet aggregates and by the upregulation of PDPN both in glioma cells and in astrocytes, reflecting the characteristics of human gliomas. Deletion of PDPN either in tumor cells or in astrocytes resulted in glioma formation with similar penetrance and grade compared with control mice. Importantly, only the lack of PDPN in tumor cells, but not in astrocytes, caused a significant reduction in intratumoral platelet aggregates, whereas in vitro, both cell types have similar platelet aggregation-inducing capacities. Our results demonstrate a causative link between PDPN and platelet aggregation in gliomas and pinpoint the tumor cells as the major players in PDPN-induced platelet aggregation. Our data indicate that blocking PDPN specifically on tumor cells could represent a novel strategy to prevent platelet aggregation and thereby reduce the risk of VTE in glioma patients.

Platelet Aggregation Induced In Vivo By Heparin And Heparin Fractions

1981 ◽  
Author(s):  
M Silane ◽  
J N Lindon ◽  
B J Ransil ◽  
R D Rosenberg ◽  
E W Salzman
Keyword(s):  
Molecular Weight ◽  
Platelet Aggregation ◽  
Reciprocal Relationship ◽  
Low Molecular Weight ◽  
Arterial Blood ◽  
Platelet Aggregate ◽  
Heparin Fractions ◽  
Platelet Aggregates

As we have reported, heparin-induced platelet aggregation in vitro varies among heparin subfractions, being generally less with lower molecular weights and having a reciprocal relationship with antithrombin affinity.We now have studied heparin-induced platelet aggregates in vivo by the technique of Wu and Hoak using arterial blood from unanesthetized rabbits. Porcine mucosal heparin was fractionated by gel filtration into high molecular weight (ave. 15,000 Daltons) or low molecular weight (ave. 6,000 Daltons) preparations. IV administration of commercial porcine mucosal heparin (spec. act. 150 u/mg) or high (spec. act. 183 u/mg) or low (spec. act. 208 u/mg) molecular weight fractions was followed by an increase in the platelet aggregate ratio compared with preinjection control values. The rise in platelet aggregate ratio with heparin was significantly different from the effect of a saline placebo (n=8) but was not significantly different among rabbits receiving the commercial heparin (n=9) or the high (n=8) or low (n=8) molecular weight preparations. Peak rise in circulating aggregate ratio occurred 2 minutes after the injection, and values returned to control levels within 15 to 30 minutes. There was no change in platelet count in blood collected in EDTA, suggesting that the aggregates were not removed from the circulation in vivo.Heparin fractions of low molecular weight were further separated according to antithrombin affinity by an antithrombin binding technique. In 8 rabbits low molecular weight/high antithrombin affinity heparin (spec. act. 480 u/mg) did not cause formation of platelet aggregates. The results were significantly different from those with commercial heparin (p=0.05) or with the other heparin fractions (p=0.06).Clinical use of low molecular weight heparin of high antithrombin affinity may lead to fewer heparin-induced platelet effects and to an improvement in anticoagulant therapy.

Platelet Function in Childhood Migraine

Cephalalgia ◽  
1985 ◽  
Vol 5 (2_suppl) ◽  
pp. 99-101 ◽  
Author(s):  
Pietro Carrieri ◽  
Fulvio Sorge ◽  
Giuseppe Orefice ◽  
Salvatore De Feo
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Plasma Levels ◽  
Childhood Migraine ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates

Platelet function in vitro and in vivo (ADP-induced platelet aggregation, circulating platelet aggregates, β-thromboglobulin plasma levels) has been studied in children with common migraine, in headache-free intervals. Migraine patients demonstrated increased circulating platelet aggregates when compared with controls. Moreover, two of ten patients had pathological β-thromboglobulin levels. These data indicate that in some children with migraine there is an abnormality of platelet function during headache-free periods.

scholarly journals Inhibition of Platelet Aggregation by Brinolase Degradation Products of Fibrinogen and Serum Albumin

1977 ◽  
Author(s):  
W. H. E. Roschlau
Keyword(s):  
Platelet Aggregation ◽  
Serum Albumin ◽  
Degradation Products ◽  
Platelet Rich Plasma ◽  
Biological Effects ◽  
Response Curves ◽  
Human Fibrinogen ◽  
Inhibition Of Platelet Aggregation

Brinolase (fibrinolytic enzyme from Aspergillus oryzae) was observed to possess significant platelet aggregation inhibitory properties during and after thrombolytic therapeutic use. These platelet effects were found in vitro to be caused in part by intermediate products of fibrinogen digestion, namely low-molecular-weight peptides of approx. MW 2500. Human fibrinogen peptides were isolated, purified, and shown to have high inhibitory activity in platelet-rich plasma. Quantitative comparisons of attainable platelet inhibition in vitro and observed responses in vivo during administration of equivalent enzyme doses, however, suggested that total available fibrinogen, even if it were entirely converted to degradation products (which it is not), would be insufficient to account for observed platelet effects of brinolase therapy.Human serum albumin is also readily degraded by brinolase. Albumin degradation products were prepared in vitro by optimal incubation with the enzyme. Dose-response curves of inhibition of platelet aggregation were obtained with lyophilized peptides in platelet-rich plasma in vitro, and significant inhibition of platelet aggregation was observed in vivo following infusion of albumin degradation products into rabbits. The enzyme doses and amounts of substrates employed in all experiments were equivalent to the conditions of therapeutic fibrinolysis.Thus, albumin degradation products are considered to contribute a significant, if not the major, portion of platelet-active intermediates during clinical brinolase therapy. Albumin cleavage, which is unique to brinolase amongst clinical fibrinolytic enzymes, was shown to have biological effects of its own, but it may also serve to protect coagulation proteins from enzymatic destruction through competition for the enzyme during systemic brinolase therapy.

Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 566-576 ◽  
Author(s):  
Mhairi J. Maxwell ◽  
Erik Westein ◽  
Warwick S. Nesbitt ◽  
Simon Giuliano ◽  
Sacha M. Dopheide ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Imaging Techniques ◽  
Platelet Aggregates ◽  
Adhesive Interactions ◽  
Membrane Tethers ◽  
Atherosclerotic Plaque Rupture

Abstract Disturbances of blood flow at sites of atherosclerotic plaque rupture are one of the key pathogenic events promoting platelet activation and arterial thrombus formation. Shear effects of platelets have been extensively investigated in vitro; however, the mechanisms by which shear promotes platelet aggregation in vivo remain incompletely understood. By employing high-resolution imaging techniques to in vitro and in vivo thrombosis models, we demonstrate a unique mechanism initiating shear-dependent platelet aggregation involving aggregate formation between discoid platelets. These discoid platelet aggregates are initially unstable and result from the development of membrane tethers between coadhering platelets. Tether formation involves the adhesive function of GPIb/V/IX and integrin αIIbβ3, and conversion of discoid platelet aggregates into stable aggregates requires released ADP. The efficiency of this process is regulated by 3 independent variables, including the reactivity of the adhesive substrate, the level of shear flow, and the platelet density at the adhesive surface. These studies identify a new mechanism initiating platelet aggregation that is critically influenced by shear, physical proximity between translocating platelets, and membrane tether formation. Moreover, they provide a model to explain how the discoid morphology of platelets facilitates the maintenance of adhesive interactions with thrombogenic surfaces under high shear stress conditions.

The Determination of Platelet Aggregation by Filtration Pressure in Circulating Dog Blood

1973 ◽  
Vol 29 (01) ◽  
pp. 201-210
Author(s):  
R. J Broersma ◽  
G. D Dickerson ◽  
M. S Sullivan
Keyword(s):  
Blood Pressure ◽  
Platelet Aggregation ◽  
Drug Effects ◽  
Arterial Circulation ◽  
Dog Blood ◽  
Platelet Aggregates ◽  
In Vitro Effects ◽  
Pressure Changes

SummaryA reproducible method is described for quantitating either spontaneous or ADP- induced platelet aggregation in circulating dog blood after heparinization. An extra- corporeal shunt containing screen material with openings 53 microns square was placed in the dog’s arterial circulation. The blood pressure was measured proximal to this filter. The blood pressure decreased upon opening the shunt to the circulation and increased when the filter became occluded. The degree and rate of aggregation was determined by means of measuring these blood pressure changes. Phase and electron microscopy demonstrated platelet aggregates occluding the filters. Platelet aggregation on the filter was experimentally accelerated by infusing ADP before the filter. The administration of ADP in concentrations between 0.625 and 10 μg/ml until occlusion, produced a dose response relationship between log of ADP concentration and rate of filter occlusion. Macrodex, a known inhibitor of platelet aggregation was given intravenously and was found to delay filter occlusion. Similar results were obtained with high intravenous doses of phenylbutazone. The method was used to compare the drug effects with their in vitro effects measured photometrically. It would appear that this technique can be used for demonstrating and quantitating the effects of drugs on the process of platelet adhesion and aggregation in vivo.

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

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