Effect of Ibuprofen on Platelet Function in Normal Subjects and Hemophiliacs

1977 ◽  
Author(s):  
B.A. McIntyre ◽  
R.B. Philp ◽  
M.J. Inwood
Keyword(s):  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Red Cell ◽  
Platelet Adhesiveness ◽  
Double Blind ◽  
Cell Counts ◽  
Hemostatic System ◽  
Anti Inflammatory

Most anti-inflammatory analgesics are contraindicated in hemophiliacs because of inhibition of platelets, erosion of gastric mucosa, and prolongation of bleeding time. New proprionic acid derivatives are claimed to have a lower incidence of gastrointestinal bleeding and less effect on the hemostatic system. One of these (ibuprofen, Motrin, Upjohn) was given (600 mg per os) to normal subjects and hemophiliacs on a random, double-blind basis (lactose placebo) and platelet adhesiveness and aggregation, platelet and red-cell counts, % packed cells, % hemoglobin and modified Ivy bleeding time were measured before and 2 and 24 hours (hr) after drug. Pre-drug and 24 hr post-drug values were normal but at 2 hr post-drug, ADP, adrenaline and collagen aggregations were inhibited and bleeding times slightly but significantly prolonged in the ibuprofen-treated normal subjects. Similar results were obtained in the ibuprofen-treated hemophiliacs but prolongation of bleeding time was not significant. In vitro studies with citrated platelet-rich plasma showed that ibuprofen inhibits platelet aggregation and synthesis of prostaglandins by platelets. Thus the results suggest that ibuprofen may be given to hemophiliacs rather than some of the older anti-inflammatory agents presently in use.

Effect of Fibrinolysis on Adhesion and Aggregation of Human Platelets

1968 ◽  
Vol 19 (03/04) ◽  
pp. 474-482 ◽  
Author(s):  
S Cronberg
Keyword(s):  
Platelet Aggregation ◽  
Connective Tissue ◽  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Glass Slide ◽  
Platelet Adhesiveness ◽  
Molecular Type ◽  
Photometric Technique

SummaryStreptokinase was infused in 7 patients with venous thrombosis. The bleeding time remained unchanged or slightly prolonged and the number of platelets did not decrease. As studied by photometric technique, platelet aggregation after addition of ADP or connective tissue suspension was not consistently changed. Platelet adhesiveness, as tested with Hellem’s whole blood method, was decreased. The platelets showed decreased adhesion and spreading on a glass slide.Addition of streptokinase in vitro to citrated platelet rich plasma in doses of 1,600–7,000 u/ml caused a release reaction after 2–3 min, and the platelets aggregated. Incubation with urokinase impaired adhesion to glass and spreading and slightly diminished aggregation by ADP or connective tissue suspension.Purified split products of D, E or high molecular type in final concentrations of 0.1–2.0 mg/ml did not aggregate platelets or influence aggregation by ADP or connective tissue suspension. A slightly decreased adhesion to glass and spreading occurred only when the doses used were large.The implications of the multifacetted findings are discussed.

The d-Enantiomer Form of Indobufen Totally Accounts for the Anti-Cyclooxygenase and Antiplatelet Activity Ex Vivo and for the Increase in Bleeding Time by Indobufen in Man

1992 ◽  
Vol 67 (02) ◽  
pp. 258-263 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
An Yan ◽  
Walter Bernini ◽  
Daniela Giannessi ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Random Sequence ◽  
Antiplatelet Agent ◽  
Antiplatelet Drug ◽  
Double Blind

SummaryIndobufen is an antiplatelet drug able to inhibit thromboxane production and cyclooxygenase-dependent platelet aggregation by a reversible inhibition of cyclooxygenase. Indobufen exists in two enantiomeric forms, of which only d-indobufen is active in vitro in inhibiting cyclooxygenase. In order to verify that also inhibition of platelet function is totally accounted for by d-indobufen, ten patients with proven coronary artery disease (8 male, 2 female, age, mean ± S.D., 58.7 ± 7.5 years) were given, in random sequence, both 100 mg d-indobufen and 200 mg dl-indobufen as single administrations in a double-blind crossover design study with a washout period between treatments of 72 h. In all patients thromboxane (TX) B2 generation after spontaneous clotting (at 0, 1, 2, 4, 6, 8, 12, 24 h), drug plasma levels (at the same times), platelet aggregation in response to ADP, adrenaline, arachidonic acid, collagen, PAF, and bleeding time (at 0, 2, 12 h) were evaluated after each treatment. Both treatments determined peak inhibition of TXB2 production at 2 h from administration, with no statistical difference between the two treatments (97 ±3% for both treatments). At 12 h inhibition was 87 ± 6% for d-indobufen and 88 ± 6% for dl-indobufen (p = NS). Inhibition of TXB2 production correlated significantly with plasma levels of the drugs. Maximum inhibitory effect on aggregation was seen in response to collagen 1.5 pg/ml (63 ± 44% for d-indobufen and 81 ± 22% for dl-indobufen) and arachidonic acid 0.5-2 mM (78 ± 34% for d-indobufen and 88 ± 24% for dl-indobufen) at 2 h after each administration. An effect of both treatments on platelet aggregation after 12 h was present only for adrenaline 2 μM (55 ± 41% for d-indobufen and 37 ± 54% for dl-indobufen), collagen 1.5 pg/ml (69 ± 30% for d-indobufen and 51 ± 61% for dl-indobufen), arachidonic acid 0.5-2 mM (56 ± 48% for d-indobufen and 35 ± 49% for dl-indobufen). The extent of inhibition of TX production and the extent of residual platelet aggregation were never significantly different between treatments. Bleeding time prolongation was similar in the two treatment groups without showing a pronounced and long lasting effect (from 7.0 ± 2.0 min to 10.0 ± 3.0 min at 2 h and 8.0 ± 2.0 min at 12 h for d-indobufen; from 6.0 ±1.0 min to 8.5 ± 2.0 min at 2 h and 8.0 ± 1.0 min at 12 h for dl-indobufen). These results demonstrate that the biological activity of dl-indobufen as an antiplatelet agent in vivo is totally accounted for by d-indobufen.

The Effect of Warfarin Sodium on the Duration of Platelet Aggregation

1967 ◽  
Vol 18 (03/04) ◽  
pp. 766-778 ◽  
Author(s):  
H. J Knieriem ◽  
A. B Chandler
Keyword(s):  
Platelet Count ◽  
Placebo Group ◽  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Platelet Rich Plasma ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Warfarin Sodium

SummaryThe effect of the administration of warfarin sodium (Coumadin®) on the duration of platelet aggregation in vitro was studied. Coumadin was given for 4 consecutive days to 10 healthy adults who were followed over a period of 9 days. The duration of adenosine diphosphate-induced platelet aggregation in platelet-rich plasma, the prothrombin time, and the platelet count of platelet-rich plasma were measured. Four other healthy adults received placebos and participated in a double-blind study with those receiving Coumadin.Although administration of Coumadin caused a prolongation of the prothrombin time to 2 or 21/2 times the normal value, a decrease in the duration of platelet aggregation was not observed. In most individuals who received Coumadin an increase in the duration of platelet aggregation occurred. The effect of Coumadin on platelet aggregation was not consistently related to the prothrombin time or to the platelet count. In the placebo group there was a distinct relation between the duration of platelet aggregation and the platelet count in platelet-rich plasma.The mean increase in the duration of platelet aggregation when compared to the control value before medication with Coumadin was 37.7%. In the placebo group there was a mean increase of 8.4%. The difference between the two groups is significant (p <0.001). Increased duration of platelet aggregation also occurred in two individuals who received Coumadin over a period of 10 and 16 days respectively.

Anti-Inflammatory Effects of Novel Standardized Platelet Rich Plasma Releasates on Knee Osteoarthritic Chondrocytes and Cartilage in vitro

2019 ◽  
Vol 20 (11) ◽  
pp. 920-933 ◽  
Author(s):  
Lucía Gato-Calvo ◽  
Tamara Hermida-Gómez ◽  
Cristina R. Romero ◽  
Elena F. Burguera ◽  
Francisco J. Blanco
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Cartilage Explants ◽  
Ex Vivo Model ◽  
Chondrocyte Viability ◽  
Platelet Concentration ◽  
The Absolute ◽  
Anti Inflammatory

Background: Platelet Rich Plasma (PRP) has recently emerged as a potential treatment for osteoarthritis (OA), but composition heterogeneity hampers comparison among studies, with the result that definite conclusions on its efficacy have not been reached. Objective: 1) To develop a novel methodology to prepare a series of standardized PRP releasates (PRP-Rs) with known absolute platelet concentrations, and 2) To evaluate the influence of this standardization parameter on the anti-inflammatory properties of these PRP-Rs in an in vitro and an ex vivo model of OA. Methods: A series of PRPs was prepared using the absolute platelet concentration as the standardization parameter. Doses of platelets ranged from 0% (platelet poor plasma, PPP) to 1.5·105 platelets/µl. PRPs were then activated with CaCl2 to obtain releasates (PRP-R). Chondrocytes were stimulated with 10% of each PRP-R in serum-free culture medium for 72 h to assess proliferation and viability. Cells were co-stimulated with interleukin (IL)-1β (5 ng/ml) and 10% of each PRP-R for 48 h to determine the effects on gene expression, secretion and intra-cellular content of common markers associated with inflammation, catabolism and oxidative stress in OA. OA cartilage explants were co-stimulated with IL-1β (5 ng/ml) and 10% of either PRP-R with 0.75·105 platelets/µl or PRP-R with 1.5·105 platelets/µl for 21 days to assess matrix inflammatory degradation. Results: Chondrocyte viability was not affected, and proliferation was dose-dependently increased. The gene expression of all pro-inflammatory mediators was significantly and dose-independently reduced, except for that of IL-1β and IL-8. Immunoblotting corroborated this effect for inducible NO synthase (NOS2). Secreted matrix metalloproteinase-13 (MMP-13) was reduced to almost basal levels by the PRP-R from PPP. Increasing platelet dosage led to progressive loss to this anti-catabolic ability. Safranin O and toluidine blue stains supported the beneficial effect of low platelet dosage on cartilage matrix preservation. Conclusion: We have developed a methodology to prepare PRP releasates using the absolute platelet concentration as the standardization parameter. Using this approach, the composition of the resulting PRP derived product is independent of the donor initial basal platelet count, thereby allowing the evaluation of its effects objectively and reproducibly. In our OA models, PRP-Rs showed antiinflammatory, anti-oxidant and anti-catabolic properties. Platelet enrichment could favor chondrocyte proliferation but is not necessary for the above effects and could even be counter-productive.

scholarly journals Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

HEM0RRHE0L0GY AND KETANSERIN

1987 ◽  
Author(s):  
J De Crée ◽  
H Geukens ◽  
H Demoen ◽  
H Verhaegen
Keyword(s):  
Platelet Rich Plasma ◽  
White Blood Cells ◽  
Vascular Diseases ◽  
Control Group ◽  
Clinical Value ◽  
Constant Amount ◽  
Double Blind ◽  
Mediated Effects ◽  
Different Levels

Red blood cell (RBC) filtration in platelet rich plasma (PRP) and platelet poor plasma (PPP) was equally decreased (p < 0.0001) in 120 patients with acute myocardial infarction (AMI) as compared to a control group. In a double-blind experiment 2 groups of 30 patients with AMI received an acute oral dose of 60 mg of ketanserin, a serotonin (5-HT) antagonist at 5-HT2-receptors, or placebo. Ketanserin treatment improved RBC filtration in PRP with an average increase of 30%. A similar experiment using PPP showed a significant increase of 10%. Filtration of plasma improved after ketanserin treatment in PRP, but not in PPP. Cross-exchange experiments showed the ketanserin-induced improvement of RBC filtration in PRP and PPP to be also plasmadependent. 5-HT in vitro at 10−9M deteriorated RBC filtration in PPP (p < 0.05), and ketanserin in vitro at 10−7M counteracted this phenomenon (p < 0.001). Finally we found that the effect of a subacute treatment with ketanserin on the filtration of RBC Suspensions, enriched with a constant amount of white blood cells (WBC), was more pronounced than on control RBC suspensions of patients with AMI.These results indicate that the impaired RBC filtration, reported in vascular diseases may be dependent on a subtle interaction between platelets, WBC, RBC and plasma. Treatment with ketanserin is capable to interrupt this vicious circle of rheological disturbances at different levels, first of all, by improving RBC deformability, but also by counteracting the platelet mediated effects on RBC and by favourably influencing the physical properties of WBC and so preventing clogging phenomena. Serotonin probably plays a pivotal role in these cascade of events and therapy with ketanserin might be of clinical value in diseases where microcirculatory flow is compromised.

DIFFERENTIAL EFFECTS OF ORAL ADMINISTRATIONS OF ACETYL SALICYLIC ACID, INDOMETHACIN AND SODIUM SALICYLATE TO HUMAN SUBJECTS ON THE FORMATION OF 12-HYDROXYEICOSATETRAENOIC BY PLATELETS

1987 ◽  
Author(s):  
E Tremoli ◽  
D Caruso ◽  
P Maderna ◽  
G Galli ◽  
R Paoletti
Keyword(s):  
Sodium Salicylate ◽  
Platelet Rich Plasma ◽  
Human Subjects ◽  
Normal Subjects ◽  
Inhibitory Effect ◽  
Washed Platelet ◽  
Single Oral Administration ◽  
Selective Ion Monitoring ◽  
Platelet Formation

The effects of a single oral administration of acetylsalicylic acid (ASA, 500 mg), indomethacin (Indo, 50 mg) and sodium salicylate (SA, 400 mg) to healthy volunteers on platelet formation of 12-hydroxyeicosatetraenoic acid (12-HETE) were evaluated. Blood was collected before, 2, 6 and 24 hours after drug administrations. Platelet rich plasma (PRP) samples were stimulated with 20 μg/ml collagen and 12-HETE levels were determined by selective ion monitoring. The effects of ASA on the same parameter were also evaluated in vitro in PRP and in washed platelet (WP) samples in the absence and in the presence of platelet poor plasma (PPP, 25-100%) or bovine serum albumin (BSA, 10-40 mg/ml). In subjects who ingested ASA, the formation of 12-HETE in PRP stimulated with collagen was significantly inhibited 2 and 6 hours after the drug administration. At 24 h 12-HETE synthesis tended to return toward basal values. In contrast the administration of a single dose of Indo or of SA did not significantly affect 12-HETE synthesis by stimulated PRP. ASA (3 mM) added in vitro inhibited 12-HETE formation in PRP but not in WP. In addition ASA inhibited 12-HETE synthesis in washed platelets resuspended either in PPP (25-100 %) or in BSA (10-40 mg/ml). It is concluded ASA, but not Indo or SA, orally administered to normal subjects inhibits 12-HETE synthesis in collagen stimulated PRP. The results obtained in vitro suggest that albumin and/or some albumin component may be responsible for the inhibitory effect of ASA on platelet 12-HETE syntesis.

scholarly journals Do patients with thromboembolic disease have circulating platelet aggregates?

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 205-209 ◽  
Author(s):  
FH Kohanna ◽  
MH Smith ◽  
EW Salzman
Keyword(s):  
Platelet Rich Plasma ◽  
Venous Blood ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
Thromboembolic Disease ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Lower Ratio

Reports of circulating platelet aggregates (ie, microemboli) in thromboembolism and other vascular disorders are based on a method (Wu and Hoak , 1974) in which venous blood is collected via scalp vein needle and tubing into either formaldehyde, which fixes aggregates, or EDTA, which disperses them. The ratio of platelet counts in platelet- rich plasma (PRP) from the two blood samples after centrifugation is interpreted as a measure of platelet aggregates in the circulation in vivo. We compared this standard Wu and Hoak technique with a modified one, in which blood was drawn directly into a syringe, and with a third method that avoided centrifugation by counting single platelets in whole blood. Both modified techniques could detect aggregates generated in vitro with adenosine diphosphate (ADP). In 12 normal subjects, the three methods were equivalent, but in 37 patients with thromboembolic disorders, the standard Wu and Hoak method gave a lower ratio than the other methods. Similar results were found in a subset of eight patients with myocardial infarction. Heparin treatment of patients did not influence the results. The data suggest that formation of platelet aggregates occurred during venipuncture. Platelets may be hyperactive in patients with thromboembolic disease and may form aggregates in vitro during collection, but the concept of chronic microembolism in such patients should be reassessed.

Coagulation Studies after Administration of a Fat Emulsion, Intralipid®

1967 ◽  
Vol 18 (03/04) ◽  
pp. 664-669 ◽  
Author(s):  
S Cronberg ◽  
Inga Marie Nilsson
Keyword(s):  
Parenteral Nutrition ◽  
Whole Blood ◽  
Clinical Relevance ◽  
Bleeding Time ◽  
Fibrinolytic System ◽  
Platelet Adhesiveness ◽  
Single Infusion ◽  
Fat Emulsion ◽  
Prolonged Bleeding Time

SummaryA single infusion of a fat emulsion, Intralipid®, used for parenteral nutrition was given to 11 healthy normals, 3 patients with von Willebrand’s disease and 3 with mild or moderately severe thrombasthenia. The infusion had no effect on coagulation or the fibrinolytic system. Platelet adhesiveness, as determined with Hellem’s whole blood method, was markedly increased but not with his plasma-ADP method or with Salzman’s method. No shortening of the bleeding time was observed in the normals or in the patients with prolonged bleeding time. The change observed in platelet adhesiveness is therefore believed to be an in vitro artefact with no clinical relevance.

The Influence of Saturated Fat, Cholesterol, Corn Oil and Linseed Oil on the ADP-Indueed Platelet Adhesiveness in the Rat

1965 ◽  
Vol 13 (02) ◽  
pp. 543-549 ◽  
Author(s):  
Arne Nordöy
Keyword(s):  
Corn Oil ◽  
Platelet Rich Plasma ◽  
Linseed Oil ◽  
Saturated Fat ◽  
Normal Diet ◽  
Cholesterol Diet ◽  
Platelet Adhesiveness

Summary1. The ADP induced platelet adhesiveness was tested in platelet rich plasma from rats on a normal diet, on a saturated fat and cholesterol diet and on this last diet supplemented with corn oil or linseed oil.2. An increased platelet adhesiveness was present in animals given a saturated fat and cholesterol diet. Addition of corn oil to this diet further increased the adhesiveness, whereas addition of linseed oil normalized the platelet adhesiveness.3. The relation between the ADP induced platelet adhesiveness tested in vitro and the tendency to thrombosis is discussed.

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