Effects “in Vitro” of Some Cardiovascular Drugs and Other Agents on Human Platelet Aggregation

SummaryThe in vitro effect of the following substances on human platelet aggregation is studied: K 4423 (a ß-blocking drug), isoproterenol, phentolamine, papaverine, methamidoline (a myolytic agent).None of these substances causes aggregation. All inhibit aggregation induced by ADP or noradrenaline, except for phentolamine, which is active only on noradrenaline- induced aggregation.Hypothesis on the mechanism of action of the compounds tested are proposed.

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Studies on in vitro effect of picotamide on human platelet aggregation in platelet-rich plasma and whole blood

Thrombosis Research ◽

10.1016/0049-3848(95)93876-2 ◽

1995 ◽

Vol 77 (5) ◽

pp. 399-410 ◽

Cited By ~ 2

Author(s):

Giovanni Anfossi ◽

Simona Parisi ◽

Isabella Russo ◽

Elena M. Mularoni ◽

Paola Massucco ◽

...

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Human Platelet ◽

Platelet Rich Plasma ◽

Human Platelet Aggregation ◽

Vitro Effect

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Apixaban, a direct factor Xa inhibitor, inhibits tissue-factor induced human platelet aggregation in vitro: Comparison with direct inhibitors of factor VIIa, XIa and thrombin

Thrombosis and Haemostasis ◽

10.1160/th10-02-0097 ◽

2010 ◽

Vol 104 (08) ◽

pp. 302-310 ◽

Cited By ~ 43

Author(s):

Xiaosui Jiang ◽

Pancras Wong

Keyword(s):

Platelet Aggregation ◽

Tissue Factor ◽

Factor Viia ◽

Human Platelet ◽

Factor Xa ◽

Coagulation Cascade ◽

Human Platelet Aggregation ◽

Direct Inhibitors ◽

Vitro Effect

SummaryApixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development. This study evaluated the in vitro effect of apixaban on human platelet aggregation induced by thrombin derived via the extrinsic pathway. Direct inhibitors of FXa (rivaroxaban), FVIIa (BMS-593214), thrombin (dabigatran, argatroban) and FXIa (BMS-262084) were included for comparison. Citrated human plateletsrich plasma (PRP) was treated with 50 μg/ml corn trypsin inhibitor (to block the contact factor pathway) and 3 mM H-Gly-Pro-Arg- Pro-OH-AcOH (to prevent fibrin polymerisation). Human tissue factor (TF) (Innovin®; dilution 1:1,000 to 1:1,500) plus 7.5 mM CaCl2 was added to PRP pre-incubated with vehicle or increasing concentrations of inhibitors. The TF-induced platelet aggregation was measured by optical aggregometry. TF produced 85 ± 3% aggregation of human platelets in the vehicle-treated group (n=10). Apixaban and other factor inhibitors, except the FXIa inhibitor, inhibited TF-induced platelet aggregation with IC50 (nM) values as follows: 4 ± 1 (apixaban), 8 ± 2 (rivaroxaban), 13 ± 1 (BMS-593214), 46 ± 1 (dabigatran) and 79 ± 1 (argatroban). BMS-262084 (IC50 = 2.8 nM vs. human FXIa) had no effect on TF-induced platelet aggregation at 10 μM. These inhibitors at 10 μM had no effect on platelet aggregation induced by ADP and collagen, as expected from their mechanism of action. This study demonstrates that inhibition of thrombin generation by blocking upstream proteases (FVIIa and FXa) in the blood coagulation cascade is as effective as direct thrombin inhibition in preventing TF-induced platelet aggregation. Under these experimental conditions, a FXIa inhibitor did not prevent TF-induced platelet aggregation.

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Inhibition of Human Platelet Aggregation by a Dibenzazepine Compound (GP 44296) and by N-(2,6-dichlorophenyl)-o-aminophenylacetic acid(GP 45840)

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y71-058 ◽

1971 ◽

Vol 49 (5) ◽

pp. 479-481 ◽

Cited By ~ 12

Author(s):

François Jobin ◽

France T. Gagnon

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Secondary Phase ◽

Human Platelets ◽

Primary Phase ◽

Human Platelet Aggregation ◽

Induced Aggregation

Studies of the aggregation of human platelets indicate that compounds GP 44296 and GP 45840 inhibit the secondary phase of ADP-induced aggregation and collagen-induced aggregation; GP 44296 also inhibits the primary phase of ADP-induced aggregation. Our results suggest that these compounds are more active on platelet behavior in vitro than phenylbutazone, oxyphenbutazone, and sulfinpyrazone.

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Sevoflurane Inhibits Human Platelet Aggregation and Thromboxane A2Formation, Possibly by Suppression of Cyclooxygenase Activity

Anesthesiology ◽

10.1097/00000542-199612000-00027 ◽

1996 ◽

Vol 85 (6) ◽

pp. 1447-1453. ◽

Cited By ~ 69

Author(s):

Hideo Hirakata ◽

Fumitaka Ushikubi ◽

Hiroshi Toda ◽

Kumi Nakamura ◽

Satoko Sai ◽

...

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Scatchard Analysis ◽

Cyclooxygenase Activity ◽

Human Platelet Aggregation ◽

Induced Aggregation

Background Halothane increases bleeding time and suppresses platelet aggregation in vivo and in vitro. A previous study by the authors suggests that halothane inhibits platelet aggregation by reducing thromboxane (TX) A2 receptor-binding affinity. However, no studies of the effects of sevoflurane on platelet aggregation have been published. Methods The effects of sevoflurane, halothane, and isoflurane were examined at doses of 0.13-1.4 mM. Human platelet aggregation was induced by adenosine diphosphate, epinephrine, arachidonic acid, prostaglandin G2, and a TXA2 agonist ([+]-9, 11-epithia-11, 12-methano-TXA2, STA2) and measured by aggregometry. Platelet TXB2 levels were measured by radioimmunoassay, and the ligand-binding characteristics of the TXA2 receptors were examined by Scatchard analysis using a [3H]-labeled TXA2 receptor antagonist (5Z-7-(3-endo-([ring-4-[3H] phenyl) sulphonylamino-[2.2.1.] bicyclohept-2-exo-yl) heptenoic acid, [3H]S145). Results Isoflurane (0.28-0.84 mM) did not significantly affect platelet aggregation induced by adenosine diphosphate and epinephrine. Sevoflurane (0.13-0.91 mM) and halothane (0.49-1.25 mM) inhibited secondary platelet aggregation induced by adenosine diphosphate (1-10 microM) and epinephrine (1-10 microM) without altering primary aggregation. Sevoflurane (0.13 mM) also inhibited arachidonic acid-induced aggregation, but not that induced by prostaglandin G2 or STA2, although halothane (0.49 mM) inhibited the latter. Sevoflurane (3 mM) did not affect the binding of [3H]S145 to platelets, whereas halothane (3.3 mM) suppressed it strongly. Sevoflurane (0.26 mM) and halothane (0.98 mM) strongly suppressed TXB2 formation by arachidonic acid-stimulated platelets. Conclusions The findings that sevoflurane suppressed the effects of arachidonic acid, but not those of prostaglandin G2 and STA2, suggest strongly that sevoflurane inhibited TXA2 formation by suppressing cyclooxygenase activity. Halothane appeared to suppress both TXA2 formation and binding to its receptors. Sevoflurane has strong antiaggregatory effects at subanesthetic concentrations (greater than 0.13 mM; i.e., approximately 0.5 vol/%), whereas halothane has similar effects at somewhat greater anesthetic concentrations (0.49 mM; i.e., approximately 0.54 vol/%). Isoflurane at clinical concentration (0.84 mM; i.e., approximately 1.82 vol/%) does not affect platelet aggregation significantly.

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The Effect of Dipyridamole and RA 233 on Human Platelet Function in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648112 ◽

1973 ◽

Vol 29 (03) ◽

pp. 694-700 ◽

Cited By ~ 4

Author(s):

Paul L. Rifkin ◽

Marjorie B. Zucker

Keyword(s):

Mechanism Of Action ◽

Human Blood ◽

Glass Bead ◽

Heart Valves ◽

Human Platelet ◽

Drug Effects ◽

Simple Relation ◽

Prosthetic Heart Valves ◽

Induced Aggregation

SummaryDipyridamole (Persantin) is reported to prolong platelet survival and inhibit embolism in patients with prosthetic heart valves, but its mechanism of action is unknown. Fifty jxM dipyridamole failed to reduce the high percentage of platelets retained when heparinized human blood was passed through a glass bead column, but prolonged the inhibition of retention caused by disturbing blood in vitro. Possibly the prostheses act like disturbance. Although RA 233 was as effective as dipyridamole in inhibiting the return of retention, it was less effective in preventing the uptake of adenosine into erythrocytes, and more active in inhibiting ADP-induced aggregation and release. Thus there is no simple relation between these drug effects.

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