scholarly journals Experimental Study of a platelet Antiaggregating Agent - Application to Ticlopidine

1977 ◽  
Author(s):  
J.F. Stoltz ◽  
M. Verry ◽  
B. Farge
Keyword(s):  
Arterial Disease ◽  
Biochemical Properties ◽  
Control Group ◽  
Group Index ◽  
Aggregation Index ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Definition Of ◽  
Induced Aggregation

The authors consider the various methods suitable for in vivo study of the anti-aggregating properties of a new drug - Ticlopidine :- study of photometric ADP-induced aggregation and screen filtration pressure in vivo in the rabbit treated per os for 5 days with doses of 25 and 50 mg/kg/d. This gave average inhibitions of 30% and 45% respectively.- study of circulating platelet aggregates using the method of Wu and Hoak after continuous infusion of ADP or of thrombin. The principle of the method involves definition of an aggregation index : the ratio between the platelet counts in the two specimens (EDTA + formol 1 % + EDTA alone).The average results showed : control group index 0.9 -after infusion of ADP 0.57- after infusion of ADP under the influence of Ticlopidine (50 and 100 mg/kg/d) 0.66 to 0.78.- the mechanism of action of the drug was studied using crossed aggregation experiments and by the study of interference with ionised or ionisable groups of the platelet membrane (isotope method, electrophoresis in liquid phase).In parallel with these experiments, studies in vivo in the rabbit and in patients (obliterative arterial disease, Raynaud’s syndrome) are in progress : interference with membrane groups, rheological properties (viscosity, rouleau formation, erythrocyte deformability) and biochemical properties (erythrocyte glycolysis enzymes).

Prevention of in vivo Platelet Aggregation by Indobufen in Angina Patients during Exercise

1981 ◽  
Vol 9 (2) ◽  
pp. 113-119 ◽  
Author(s):  
E M Pogliani ◽  
R Fantasia ◽  
C Perini ◽  
G Corvi
Keyword(s):  
Platelet Aggregation ◽  
Bicycle Ergometer ◽  
Crossover Design ◽  
Double Blind ◽  
Before And After ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions

Platelet aggregation induced by 3 concentrations of ADP and collagen was assessed in thirty patients with stable angina, before and after exercise with a bicycle ergometer. The patients received a single oral 200 mg dose of indobufen and placebo according to a crossover design in double-blind conditions. Platelet sensitivity to both aggregating agents increased when exercise was carried out after placebo, whereas indobufen markedly inhibited ADP- and collagen-induced aggregation. Circulating platelet aggregates increased in some patients during exercise after placebo but not after indobufen. These results suggest that effort may be an important factor in activation of platelet functions and that the use of drugs blocking the arachidonate pathway and the release reaction may be appropriate in patients with angina.

Detection of Circulating Platelet Aggregates in Thrombo-Embolic Disease

1979 ◽  
Author(s):  
Marie Scrobohaci ◽  
Teodora Petrilă ◽  
M. Constantinescu ◽  
Magdolnra Stadler ◽  
Doina Mihšilă ◽  
...  
Keyword(s):  
Body Weight ◽  
Normal Subjects ◽  
Experimental Conditions ◽  
Aggregation Index ◽  
Leriche Syndrome ◽  
Circulating Platelet Aggregates ◽  
Valvular Diseases ◽  
Platelet Aggregates ◽  
Iliac Occlusion

SummaryThe method of Wu and Hoak in determining circulating platelet aggregates in vivo was used.In different cardiac and vascular states, a low aggregation index is found: aorto-iliac occlusion(Leriche syndrome)- 38 cases(index X ± SD 0.52 ±0.05 in comparison with normal subjects 0.91± 0.05):valvular diseases - 24 cases (0.40±0.006); during extracorporeeal circulation- 14 cases(0. 5±0.021) ; thrombophlebitis-25 cases(0.84±0.065).After an antiaggregation treatment(Dipiridamol) in 12 cases of aorto - iliac ocdusion the value of the aggregation index normalised(0.84±0.065) Experimentally, lo rabbits were perfused with thrombin so ution(2 u./body weight k.);the lower values of the aggregation index(0.91±0.085 before and 0.43±0.035 after the thrombin perfusion) prove the fidelity of the method.The simplicity of the technique, the reproductibility in experimental conditions and the normalisation of the values after treatment prove the practical value in determining the circulating platelet aggregates.

Detection of Circulating Platelet Aggregates in Thromboembolic Disease

1979 ◽  
Author(s):  
Lorène Scrobohaci Marie ◽  
Teodora Petrilǎ ◽  
M. Constantinescu ◽  
Magdolna Stadler ◽  
Doina Mihǎilǎ ◽  
...  
Keyword(s):  
Normal Subjects ◽  
Thromboembolic Disease ◽  
Experimental Conditions ◽  
Aggregation Index ◽  
Leriche Syndrome ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Aortoiliac Occlusion ◽  
Iliac Occlusion

Summary: The method of Wu and Hoak in det rmining circulating platelet aggregates in vivo was used.In different cardiac and vascular states, a low aggregation index is found: aorto-iliac occlusion (Leriche syndrome)- 38 csses(index X ± SD 0.52 ± 0.05 in comparison with normal subjects 0.91 ± 0.05); valvular diseasses (0.40±0.006); during extracorporeeal circulation - 14 cases (0.5±0.02l); thrombophlebitia-25 casea(0.84±0.065).After an antiaggaagation treatment (Dipiridamol) in 12 cases of aortoiliac occlusion the value of the aggregation index normalised(0.84±0.065) Experimenntlllly, 10 rabbits were perfused wi th thrombin soution (2 u./body woight k.); the lower values of the aggreeation index (0.91±0.085 brfore Emd 0.43±0.035 after the thromhin perfuaion) prove the fidelity of the method.The simplicity of the technique, the reproducti bili ty in experimental conditions and the normalisation of the valuwa after treatment prove the practical value in determining the circulating platelet aggregates.

In Vivo Platelet Activation Following Myocardial Infarction and Acute Coronary Ischaemia

1982 ◽  
Vol 48 (02) ◽  
pp. 133-135 ◽  
Author(s):  
A Hughes ◽  
S Daunt ◽  
G Vass ◽  
J Wickes
Keyword(s):  
Myocardial Infarction ◽  
Chest Pain ◽  
Acute Chest Pain ◽  
Normal Subjects ◽  
Specific Protein ◽  
Control Group ◽  
Platelet Activity ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates

SummaryForty-seven patients presenting with acute chest pain had in vivo platelet activity assessed by measuring plasma levels of the platelet-specific protein beta thromboglobulin (BTG), and by screening for the presence of circulating platelet aggregates. Nineteen patients with transmural myocardial infarction (MI), 21 patients with acute coronary ischaemia (CI), and 7 patients with non-cardiac chest pain (NCCP) were investigated in a serial study and compared with a normal control group. The means of all BTG determinations in the MI (34, ± SD = 21-57) and CI (33, ± SD = 19-57) groups were significantly higher than those in the NCCP group (24, ± SD = 17-34; p Ã0.01) and normal subjects (22,5, ± SD = 14-37; p Ã0.001). There was no difference in BTG between those with MI or CI, nor between the NCCP group and normal subjects. Raised numbers of circulating platelet aggregates could not be detected in either MI or CI. The mean BTG levels in both MI and CI patients were significantly raised, compared to normal subjects, on the first day of admission to hospital and remained so on each of the subsequent nine days. Neither heparin plus warfarin nor sulphinpyrazone had any significant effect in lowering BTG levels. 15/40 patients (37.5%) following MI and CI had repeatedly raised BTG levels throughout the study period, and it is suggested that these patients represent an “at risk” group that may benefit from anti-platelet therapy in secondary prevention studies.

scholarly journals Comparative studies of the anti-thrombotic effects of saffron and HongHua based on network pharmacology

2020 ◽  
Vol 19 (7) ◽  
pp. 1441-1448
Author(s):  
Jinyan Jiang ◽  
Susu Lin ◽  
Qiaoqiao Li ◽  
Shanshan Jiang ◽  
Yingjie Hu ◽  
...  
Keyword(s):  
Animal Experiments ◽  
Blood Stasis ◽  
Erythrocyte Aggregation ◽  
Network Pharmacology ◽  
Control Group ◽  
Clotting Time ◽  
Aggregation Index ◽  
Model Control

Purpose: To investigate the comparative anti-thrombotic effects of saffron and Honghua, and also to explore possible mechanisms in thrombosis based on network pharmacology. Methods: A network pharmacology model was used for bioactive components, targets and pathways for saffron and HongHua via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, Genecard, Uniprot and KEGG databases. In animal experiments, 72 rats were randomly divided into 9 groups: normal control group (NC), model control group (MC), crocetin groups (80, 40, 20 mg/kg), hydroxysafflor yellow A(HSYA) groups (80, 40, 20 mg/kg), and aspirin group (40 mg/kg). Using in vitro thrombosis models and an acute blood stasis model in vivo, the anti-thrombotic effects of these treatments on clotting time, hemorheology parameters, Thromboxane B2 (TXB2), plasmin activator inhibitor (PAI), protein C (PC), protein S (PS), and thrombinantithrombin complex (TAT) were determined and comparisons made for saffron and HongHua. Results: Five potential compounds, 16 anti-thrombotic targets and 27 pathways were predicted for saffron, while 22 compounds, 37 disease targets and 35 pathways were found for HongHua (p < 0.05). Pharmacological experiments revealed that crocetin and HSYA had significant effects on thrombus length, thrombus wet/dry mass, whole blood viscosity (WBV), erythrocyte aggregation index (EAI), clotting time and D-dimer for the high and middle groups. Unlike HSYA, crocetin also had significant and dose-dependent effects on PAI, prothrombin fragment 1+2 (F1+2) and PS and had highly significant effects on TXB2 and TAT. Conclusion: This research provides a systematic, comprehensive and comparative analysis of component, target and anti-thrombotic pathways of saffron and HongHua based on network pharmacology, and also shows that saffron has more significant anti-thrombotic effect than HongHua. Keywords: Saffron; HongHua; Network pharmacology; Anti-thrombosis; Network model

scholarly journals The Induction of Platelet Aggregates in Healthy Subjects by Venousocclusion

1977 ◽  
Author(s):  
D.A. F. Chamone ◽  
J. Vermylen
Keyword(s):  
Healthy Subjects ◽  
Light Transmission ◽  
Diastolic Pressure ◽  
Platelet Rich Plasma ◽  
In Vivo Evaluation ◽  
Modified Method ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Set Up

Circulating platelet aggregates have been observed in various clinical conditions (Wu and Hoak, Lancet, 1974, ii, 924). Using a slightly modified method, we have found that platelet aggregates can be induced in vivo in healthy subjects.Nine volunteers (7 males, 2 females, age 23-38 years) were studied. Blood was drawn from an antecubital vein of one arm immediately before and of the other arm after twenty minutes of occlusion midway between systolic and diastolic pressure. The ratio of the platelet count in platelet-rich plasma (PRP) obtained from blood collected on forma lin-EDTA to that from blood collected on EDTA only was 0.934 + 0.028 (mean ± S.E .) before and 0.768 ± 0.033 after occlusion (p < 0.001 ). Spontaneous aggregation in PRP, measured as percent increase in light transmission during 10 minutes of stirring in the a gg re gome ter, was 4 .20 ± 1.17 before and 3 .80 + I .69 after occlusion (p > 0 .1).This system may help elucidate some of the mechanisms involved in the generation of circulating platelet aggregates. It may also constitute a simple set-up for the in vivo evaluation of drugs affecting platelet function.

Increased Plasma Fibrinogen and Platelet-Aggregates in Type II Hyperlipoproteinaemia

1979 ◽  
Author(s):  
J.L.H.C. Third ◽  
G.D.O. Lowe ◽  
M.M. Drummond ◽  
W.F. Bremner ◽  
T.D.V. Lawrie ◽  
...  
Keyword(s):  
Plasma Lipids ◽  
Young Patients ◽  
Adult Life ◽  
Arterial Disease ◽  
Arterial Injury ◽  
Plasma Fibrinogen ◽  
Type Ii ◽  
Platelet Aggregate ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates

Plasma-fibrinogen and circulating platelet-aggregates (method of Wu and Hoak1) were measured in 21 patients with Type II hyperlipoproteinaeima and 21 matched control subjects. Patients with hyperlipoproteinaemia had increased levels of fibrinogen (3.5 g/l ± SEM 0.2 vs. 2.5 g/l±0.1, p(0.01) and platelet-aggregates (platelet aggregate ratio 0.71 vs. 0.65, p(0.01). Young patients with hyperlipoproteinaemia had prematurely high fibrinogen levels, and the normal fibrinogen rise durina adult life was abolished. There were no significant correlations between fibrinogen, platelet-aggregates, and plasma lipids (cholesterol, cholesterol fractions, or triglyceride). High librinogen and platelet-aggregate levels may play a part in the development of the premature arterial disease associated with Type II hyperlipoproteinaemia, or may be markers of arterial injury. 1Wu, K.K., Hoak, J.C.Lancet, 1974, ii, 924.

Effect of Indobufen (K 3920) A New Antiplatelet Agent After Oral Administration in Patients with Vascular Diseases

1979 ◽  
Author(s):  
S. Coccheri ◽  
G.C. Fortunato
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Agent ◽  
Vascular Diseases ◽  
Maximal Amplitude ◽  
Marked Inhibition ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Induced Aggregation

The antiaggregating effect of a new butyric acid derivative, indobufen (K 3920), was investigated in 30 patients with vascular diseases. A between-patient study was performed by administering 50 mg b.i.d. or 100 mg b.i.d. for 14 days to 2 groups of patients. A series of platelet function and clotting parameters were recorded at the end of the treatment period, both 2 and 24 h after the last administration.A marked inhibition of platelet aggregation was observed in both groups, as shown from the significant changes in maximal amplitude, reaction time and slope of ADP- and collagen-induced aggregation wave.Similar results were observed at the Breddin test in both groups of patients and at all experimental times.Platelet adhesiveness was also reduced and circulating platelet aggregates were normalized in all patients who had abnormal basal values.A shortening of euglobulin lysis time was observed 2 h but not 24 h after administration of both doses.Tolerability was excellent.Indobufen appears to be a promising drug for treatment of vascular diseases where platelet aggregation is involved.

Platelet Function Parameters In Diabetic Patients

1981 ◽  
Author(s):  
A I Woods ◽  
S S Meschengieser ◽  
N M Sutton ◽  
M A Lazzari
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Diabetic Patients ◽  
Circulating Platelet Aggregates ◽  
Diabetic Population ◽  
Platelet Aggregates ◽  
Spontaneous Platelet Aggregation ◽  
Age Range ◽  
Induced Aggregation ◽  
Ristocetin Cofactor

Abnormalities in platelet function tests have already been described in diabetic patients reflecting platelet hyperreactivity. An attempt to determine which of the tests seemed to be more affected in the diabetic population was done in a group of 34 diabetic patients (20 men and 14 women, age range 15-76). The tests performed included assay of Ristocetin Cofactor (McFarlane et al.) circulating platelet aggregates (CPA) (Wu-Hoak) and platelet aggregation induced by ADP in low concentration (0.6 x 10-6M) and Bovine Factor VIII (0.001 U/ml). In matched controls only 3.5% had a positive aggregation induced by Bovine F VIII and with ADP (0.6 x 10-6M% ) the extent of maximum aggregation was 30%.In 15 of the 34 patients (44%) aggregation induced by ADP in high dilution was greater than 50% and this was the test more frequently affected. The level of Ristocetin Cofactor was increased (>160%) in 12 of 34 patients (35%) and aggregation induced by BF VIII was positive also in 12 patients (35%). The detection of CPA was positive in 9 patients (26%). Two patients had spontaneous platelet aggregation and in them all the other tests performed were also positive. Three patients had 3 of the tests altered, and 11 patients only had 2 affected tests.The assay more affected was the ADP induced aggregation followed by the Ristocetin Cofactor levels and BF VIII induced aggregation. The test less affected was the CPA. A correlation with clinical data will be mentioned.

scholarly journals PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2241-2246 ◽  
Author(s):  
Michael P. Reilly ◽  
Uma Sinha ◽  
Pierrette André ◽  
Scott M. Taylor ◽  
Yvonne Pak ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Immune Complex ◽  
Transgenic Mouse Model ◽  
Control Group ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Syk Inhibitor ◽  
Induced Aggregation

AbstractHeparin-induced thrombocytopenia (HIT) is a major cause of morbidity and mortality resulting from the associated thrombosis. Extensive studies using our transgenic mouse model of HIT have shown that antibodies reactive with heparin-platelet factor 4 complexes lead to FcγRIIA-mediated platelet activation in vitro as well as thrombocytopenia and thrombosis in vivo. We tested PRT-060318 (PRT318), a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis. The Syk inhibitor PRT318 thus prevented both HIT immune complex-induced thrombocytopenia and thrombosis in vivo, demonstrating its activity in HIT.

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