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.

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.

Coagulation And Hem0Rhe0L0Gy In Cerebrovascular Disease. Differences Reated To Angiographic Findings And Sex

1981 ◽  
Author(s):  
S Coccheri ◽  
G Palareti ◽  
A Andreoli ◽  
M Poggi
Keyword(s):  
Cerebrovascular Disease ◽  
Erythrocyte Deformability ◽  
Cat Scan ◽  
Lysis Time ◽  
Arterial Lesions ◽  
Euglobulin Lysis Time ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Aortic Arch Angiography ◽  
Angiographic Findings

A series of 102 cerebrovascular patients (CVP) investigated with aortic arch angiography, carotidography and CAT scan, were classified clinically in STROKE (55) and TIA (47) and pathologically as having (IAL, 51) or having no (NIAL, 51) identifiable arterial lesions. Coagulation and hemorheologic tests were performed at least 3 months after STROKE or 1 month after a TIA episode. All CVP as compared to controls (84) had significantly higher fibrinogen (Fg), F VIII AHF and RAg, blood (BV) and plasma (PV) viscosity, and poorer erythrocyte deformability (ED, as filtered erythrocyte volume, FEV), but no differences in euglobulin lysis time (ELT) even after venostasis (ELTV) and in circulating platelet aggregates (CPA, as 1/PAR). IAL vs NIAL CVP had higher Fg (mg% 285±74 vs 241±64; p<0.005); a trend to higher BV (cp 4.64±0.5 vs 4.53±0.6) and PV (cp 1.63±0.15 vs 1.58±0.15), but no differences in other parameters. In the subgroup IAL-STROKE more CPA (1/PAR 121±18) were found vs IAL-TIA (1/PAR 104±13; p<0.05). When compared to sex-matched controls CV males had more Fg (269±36 vs 220±38; p<0.01), higher BV (p<0.05) and PV (1.61±0.16 vs 1.45±0.13; p<0.001), and poorer ED (FEV ml/min 7.41±2.8 vs 10.6±3.2; p<0.005). CPA were higher in CV males than in CV females (1/PAR 122±31 vs 96±36, p<0.05). Conversely, CV females differed from their controls only for a higher PV (p<0.05). This study points out that most of the parameters considered, are especially altered in CV males rather than in CV females, thus suggesting sex-related differences in response to drugs acting on haemostasis and rheology in CV diseases.

Effect of Indobufen on Platelet Functions in Angina Patitents at Rest and During Exercise

1979 ◽  
Author(s):  
E. Pogliani ◽  
R. Fantasia ◽  
E. Polli
Keyword(s):  
Platelet Aggregation ◽  
Stable Angina ◽  
Serotonin Release ◽  
Double Blind ◽  
Before And After ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions ◽  
Stimulation Of

Platelet aggregation induced by 3 concentrations of ADP and collagen was assessed in 30 patients with stable angina before and after exercise with bicyle ergometer. The patients received a single Oral 200 mg dose of indobufen and placebo according to a cross-over design in double-blind conditions. An increase in platelet sensitivity to both aggregating agents occurred 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. In 20 patients 14C-serotonin release induced by collagen in PRP was investigated. The release was increased when placebo was administered before exercise but it was inhibited when indobufen was given before exercise. In the same patients MDA levels after thrombin-induced stimulation of platelets in PRP increased during exercise after placebo but decreased during exercise 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.

Ticlopidine Facilitates the Deaggregation of Human Platelets Aggregated by Thrombin

1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Platelet Aggregation ◽  
Prostaglandin E1 ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Before And After ◽  
Normal Human ◽  
Platelet Aggregates ◽  
Induced Aggregation

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.

Effects of Bupranolol, a New β-Blocker, on Platelet Functions of Rabbit and Human in Vitro

1976 ◽  
Vol 36 (02) ◽  
pp. 376-387 ◽  
Author(s):  
Teruhiko Umetsu ◽  
Kazuko Sanai ◽  
Tadakatsu Kato
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Human Platelets ◽  
Rabbit Platelet ◽  
Rabbit Platelets ◽  
Β Blocker ◽  
Platelet Aggregates ◽  
Induced Aggregation ◽  
Platelet Functions

SummaryThe effects of bupranolol, a new β-blocker, on platelet functions were investigated in vitro in rabbits and humans as compared with propranolol, a well-known β-blocker. At first, the effect of adrenaline on ADP-induced rabbit platelet aggregation was studied because adrenaline alone induces little or no aggregation of rabbit platelets. Enhancement of ADP-induced rabbit platelet aggregation by adrenaline was confirmed, as previously reported by Sinakos and Caen (1967). In addition the degree of the enhancement was proved to be markedly affected by the concentration of ADP and to increase with decreasing concentration of ADP, although the maximum aggregation (percent) was decreased.Bupranolol and propranolol inhibited the (adrenaline-ADP-)induced aggregation of rabbit platelets, bupranolol being approximately 2.4–3.2 times as effective as propranolol. Bupranolol stimulated the disaggregation of platelet aggregates induced by a combination of adrenaline and ADP, but propranolol did not. Platelet adhesion in rabbit was also inhibited by the β-blockers and bupranolol was more active than propranolol. With human platelets, aggregation induced by adrenaline was inhibited by bupranolol about 2.8–3.3 times as effectively as propranolol.From these findings. We would suggest that bupranolol might be useful for prevention or treatment of thrombosis.

Prevention of Platelet Hyperaggregation during Coronary Angiography

1986 ◽  
Vol 14 (4) ◽  
pp. 185-187
Author(s):  
V Ammaturo ◽  
C Perricone ◽  
B Zuccarelli ◽  
N Mininni ◽  
L Colussi ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ventricular Fibrillation ◽  
Coronary Angiography ◽  
Cardiovascular Disorders ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Platelet Hyperaggregation

The authors previously reported an increase in platelet aggregation in the days after coronary angiography, accompanied at times by worrying cardiovascular disorders (ventricular fibrillation in one case, death in two others). In the present study, ten patients received a platelet antiaggregating drug (ticlopidin) 5 days before their coronary angiography. No significant changes were detected in the test for circulating platelet aggregates (CPA test) in these patients.

scholarly journals Circulating Platelet Aggregates During Emotional Stress and Cigarette Smoking

1977 ◽  
Author(s):  
G.F. Gensini ◽  
R. Abbate ◽  
D. Prisco ◽  
G.G. Neri Serneri
Keyword(s):  
Platelet Aggregation ◽  
Medical Students ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Emotional Stress ◽  
Predictive Value ◽  
Normal Values ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Clinically Significant

Increased platelet aggregation has been observed in various hypercoagulable states, but its predictive value for thrombosis is so far uncertain. We studied the effect of emotional stress and of cigarette smoking on circulating platelets by platelet aggregates ratio (PAR) according to Wu and Hoak (1974.) in medical students aged 20-22 years. The emotional stress was undergoing a University examination.PAR was measured immediately before the examination, at the end and 15 and 30 min after the examination.PAR was significantly lowered in all the subjects at the end (P<0.0l) and after 15 min (P<0.0l) but returned toward normal values after 30 min. The decrease of PAR suggests the production of reversible circulating platelet aggregates. The effect of smo=king a cigarette has been investigated in 8 students. PAR has been determined before smoking, at the end and after 2,5 and 10 min. Smoking lasted 4 min. In 5 subjects we observed a decrease of PAR at 2 min (P< 0. 01), whereas at 5 and 10 min PAR value became normal. Lettuce cigarette smoke did not affect PAR value. Our results indicate that: 1) – Platelet aggregates are very easily produced in circulating blood; 2)- A low value of PAR does not necessarily indicate a platelet hy=peraggregability clinically significant.

scholarly journals ‘In Vivo’ and ‘In Vitro’ Effects of Some Vasoactive Drugs on Platelet Function and on Coagulation/Fibrinolysis System

1977 ◽  
Author(s):  
A.G. Dettori ◽  
O. Ponari ◽  
C. Manotti ◽  
A. Megha ◽  
M. Pini
Keyword(s):  
Platelet Function ◽  
Vasoactive Drugs ◽  
Platelet Function Tests ◽  
Lysis Time ◽  
Low Concentrations ◽  
Euglobulin Lysis Time ◽  
In Vitro Effects ◽  
Induced Aggregation

Three substances widely used as vasoactive drugs are known to have an inhibiting effect on platelet aggregation ‘in vitro’. We investigated the changes induced on thrombelastogram, routine clotting tests, euglobulin lysis time (ELT), platelet count, aggregation, and adhesiveness by i, v. administration of these drugs to man. The same indices were also studied ‘in vitro’ by adding comparable concentrations of the substances to human blood or plasma.Aminophilline did not produce any significant variation in ADP-or collagen-induced aggregation either ‘in vitro’ (50 to 200 μg/ml) or ‘in vivo’ (240 mg). A trend to disaggregation was seen only in a few cases. Shorter ELT were found 30 and 120 minutes after injection.A papaverine derivative (Metaverinum, 150 mg) showed a similar ‘in vivo’ pattern: minor changes in platelet function tests and a moderate activation of fibrinolysis were seen. The drug acted ‘in vitro’ as a powerful inhibitor of aggregation (from 30 µg/ml)while fibrinolysis was only activated at the highest concentration (120 µg/ml).Bencyclan, capable of inhibiting platelet function ‘in vitro’ at very low concentrations (0.25µM) did not show similar effects ‘in vivo’ (50 mg) apart from a reduced platelet adhesiveness to glass.

Requirement Of Fibrinogen And Calcium For Inter-Platelet Bridges In Platelet Aggregation: A Hypothesis

1981 ◽  
Author(s):  
Elizabeth Kornecki ◽  
Stefan Niewiarowski
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Proteolytic Enzymes ◽  
Divalent Cations ◽  
Platelet Surface ◽  
Fibrinogen Binding ◽  
Platelet Aggregates ◽  
High Concentrations ◽  
Induced Aggregation ◽  
Aggregation Of Platelets

Fibrinogen and calcium are required for the aggregation of platelets stimulated by ADP or pre-treated with proteolytic enzymes. Specific platelet surface fibrinogen binding sites (receptors) are exposed after platelets are stimulated by ADP or pre-treated with Chymotrypsin or pronase. It has previously been shown in our laboratory that an intact, symmetrical fibrinogen molecule is essential for fibrinogen binding and fibrinogen-induced aggregation of both ADP-stimulated and proteolytically-treated platelets. Here we propose that the mechanism by which fibrinogen and calcium aggregate platelets is by forming inter-platelet bridges linking the fibrinogen receptors of adjacent platelets together. In support of this proposition are the following new lines of evidence: 1) The fibrinogen-induced aggregations of ADP-stfiliulated or proteolytically-treated platelets are inhibited by high concentrations of fibrinogen (Ki=2.6 and 8.5 × 10 5M, respectively). The fibrinogen binding sites on adjacent platelets, at these concentrations, would be saturated by fibrinogen and therefore no inter-platelet fibrinogen bridges could be formed to hold the platelets together. 2) ADP-stimulated or chymotrypsin-treated platelets aggregated by fibrinogen are deaggregated by Chymotrypsin or pronase and this deaggregation coincides with the loss of 125I-fibrinogen from the platelet surface. 3) Preincubation of platelets with EDTA results in inhibition of both platelet aggregation and 125I-fibrinogen binding. Following the aggregations of ADP-stimulated or of chymotrypsin-treated platelets by fibrinogen, the addition of EDTA to the platelet aggregates results in both their deaggregation and their loss of bound 125I-fibrinogen. Thus it appears that divalent cations, especially calcium, are essential for the formation of fibrinogen-linked platelet aggregates.

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