Yoshio Oura

Inhibitory effect of vitamin E (α -tocopherol) on spontaneous platelet aggregation in whole blood

Abstract Vitamin E (D-α-tocopherol) inhibited spontaneous human platelet aggregation in whole blood in the 20–200 μ g/ml range. When α -tocopherol (20 μ g/ml) and aspirin (0.5 mM), or α -tocopherol and the mixture of phosphocreatine (1.5 mM) and creatine phosphokinase (50 U/ml) (CP/CPK) were added to this reaction system, a synergic inhibitory effect on aggregation was observed. On the other hand, when both α -tocopherol and the specific inhibitor of platelet activating factor (CV-3988 : 0.38 mM) were added to this system, the inhibition was the same as that caused by the addition of CV-3988 alone, suggesting there was no synergism, i.e., that the effect of α -tocopherol is related to the inhibition of platelet activating factor (PAF)-induced platelet aggregation in whole blood. However, α -tocopherol (20 or 50 μ g/ml) did not inhibit PAF (10 nM) induced platelet aggregation in platelet rich plasma (PRP). These results suggest that the inhibition of platelet aggregation in whole blood by α -tocopherol is due to the inhibition of PAF synthesis, and is unrelated to adenosine diphosphate (ADP) or thromboxane A2.

Combination effect of eicosapentaenoic acid and platelet suppressive agents on platelets

Abstract The effect of highly purified eicosapentaenoic acid in a soft capsule (EPA-E) combined with acetylsalicylic acid (ASA) or ticlopidine (TIC) on platelets in patients with chronic cerebral ischemia was investigated. Patients in the first group were given EPA-E (1800 mg/d) alone for 4 weeks. In the second and third groups, patients were give ASA (162 mg/d) or TIC (200 mg/d) only for the first 4 weeks, then EPA-E (1800 mg/d) was added to the prescription for the last 4 weeks. Platelet function was tested by examining platelet aggregation, platelet adhesiveness, and the plasma level of beta-thromboglobulin (β-TG). Administration of EPA-E alone did not cause any changes in the platelet function test results. ASA alone significantly inhibited only the platelet aggregation induced by collagen, while the addition of EPA-E led to significant inhibition of aggregation induced by adenosine diphosphate (ADP) and the plasma level of β-TG. TIC alone showed significant inhibition in all tests except for the aggregation induced by 1 μm ADP. No additional effect of EPA-E was observed. These results suggest that the combination of EPA-E and ASA, each of which alone had only a partial effect on platelets, is effective for suppressing platelet functions. However, EPA-E contributed no significant effect to TIC, which by itself effectively inhibited platelet functions.

Effect of Plasminogen Activator on Platelet Aggregation

The clinical efficacy of thrombolytic therapy with plasminogen activator (PA) may be partly influenced by its effect on blood platelets. We investigated the effect of PA on human platelet aggregation using as PAs, staphylokinase (SAK), which has been found to have higher specific thrombolytic properties and less fibrinogenolytic properties than those of streptokinase, and also recombinant tissue-type plasminogen activator (TPA). Platelet aggregation was evaluated using platelet-rich plasma (PRP) or washed platelet suspension (WP). To examine the effects of PA, platelets were preincubated with PA (final concentration range: 0.001–100 μg/ml) at 37°C for 30 minutes. Both TPA and SAK inhibited platelet aggregation induced by collagen and ADP in PRP only at high concentrations (50–100 μg/ml). Both agents did not inhibit PRP aggregation induced by ristocetin. Although TPA and SAK did not inhibit platelet aggregation induced by collagen in WP which contained 0.5 mM calcium and 25 mg/dl fibrinogen, both agents inhibited aggregation under the same conditions in WP when the platelets had been preincubated with these agents and plasminogen (0.5 U/ml). The most effective concentrations were 100 μg/ml for TPA and 1 μg/ml for SAK. These effects were inhibited by adding aprotinin (1000 U/ml). We concluded from these results that, PA can inhibit platelet aggregation in WP by generating of plasmin and/or fibrinogen degradation products, but is only partially effective in PRP, possibly because of the existence of plasmin inhibitor.