The Combined Effect of Dipyridamole and Acetyl Salicylic Acid on Platelet Function and Bleeding Time : Evaluation of Dose for the Prophylaxis of Thrombosis

1979 ◽  
Author(s):  
A.F. Penny ◽  
M. J. Crow ◽  
S. M. Rajah ◽  
R.C. Kester

The interaction of Dipyridamole (DPM) and Acetyl Salicylic Acid (ASA) on volunteers was investigated. ASA was given in single doses (multiples of 60mg) at 2 week intervals. DPM (multiples of 25 mg) was given tds for 2 days with a single dose of DPM and ASA on the morning of day 3. Bleeding time and platelet functions were performed 2 hours after each dose. ASA 300mg maximally inhibited aggregation, adhesion and PF4 release. Lower doses of ASA gave significant reductions in collagen aggregation at 120 mg, adhesion at 180mg and PF4 at 240mg. DPM 25mg tds produced reductions in collagen aggregation, adhesion and PF4. Maximal inhibition of platelet function without alteration in bleeding time was achieved by 50mg tds DPM + 180mg ASA or 75mg tds DPM + 120mg ASA. Bleeding time was normal with ASA 120mg, 180mg; prolonged at 300mg and 1000mg and tending to be normalised by 2g. Addition of DPM 75mg tds at each dose of ASA made no alteration in bleeding time. There was a cumulative effect of ASA on bleeding time. Combined DPM mg tds and low dose ASA present a balanced anti thrombotic regimen probably both inactivating thromboxane A2 production and enhancing prostacyclin activity. This dose combination is worthy of evaluation as an additional group, in trials.

1979 ◽  
Author(s):  
C.N. McCollum ◽  
S.M. Rajah ◽  
M.J. Crow ◽  
R.C. Kester

The effect of Acetyl Salicylic Acid (ASA), Dipyridamole (DPM) and in combinations on the response of platelets to woven Dacron perfused in an artificial circulation was investigated. Circuits were perfused by heparinised blood donated by 6 volunteers after each had taken: -1) No drugs 2) ASA 300mg tds 3) DPM 100mg qds 4) ASA 300mg + DPM 75mg tds 5) ASA 80mg + DPM 75mg tds 6) ASA 80mg tds, for 1 week. Bleeding times were performed prior to each donation. Platelet functions were estimated during perfusion. Each grafts surface was examined by scanning electron microscopy (SEM) at the end of perfusion.Platelet inhibition by low dose ASA + DPM was accompanied by less extension of bleeding time, and we suggest that such combination may protect patency in Dacron grafts at risk.


1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.


1987 ◽  
Vol 48 (4) ◽  
pp. 501-504 ◽  
Author(s):  
C. Doutremepuich ◽  
D. Pailley ◽  
M.C. Anne ◽  
O. de Séze ◽  
J. Paccalin ◽  
...  

1991 ◽  
Vol 35 (4) ◽  
pp. 311-317 ◽  
Author(s):  
M. Toppozada ◽  
E.A. Darwish ◽  
Y.F. Osman ◽  
M.S. Abd-Rabbo

1979 ◽  
Author(s):  
G. Bremer ◽  
O. Richter ◽  
E. Jacobi

The mean Platelet survival is an in-vivo parameter in the analysis of platelet function. Thromboembolic diseases are associated with shortened platelet survival, because platelets are consumed in the thrombus generanation. Platelet survival therefore is an parameter for controlling the effectiveness of antiplatelet drugs. In order to investigate the effect of several antiplatelet drugs, platelet survival is measured in Patients suffered from long-standing diabetes mellitus with secondary complications with and without the following antiplatelet drugs: 3 times of 500 mg per day SH 1117 (Sulfinylaceticacidemethylester), 3 times of R 149 per day (75 mg Dipyridamole + 330 mg Acetyl-Salicylic-Acid) and a third group treated with 3 times per day 150 mg Anturano + 150 mg Dipyridamole. The shortened platelet survival in Diabetes mellitus can be normalized by R 149, whilest SH 1117 increases the platelet survival only moderately. Under the treatment with Anturano combined with Dipyridamole platelet survival is prolonged, but not normalized.


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