Stefania Favilla

Increased fibrinopeptide A formation and thromboxane A2 production in patients with ischemic heart disease: Relationships to coronary pathoanatomy, risk factors, and clinical manifestations

In 98 patients with ischemic heart disease (IHD), independent of their clinical status (previous myocardial infarction, spontaneous angina or effort angina), a hypercoagulable state (indicated by significant elevation of fibrinopeptide A plasma level) and an increased platelet biologic activity were observed. Moreover, plasma fibrinopeptide A concentration and platelet aggregation were remarkably higher in patients with frequently occurring spontaneous clinical manifestations (active disease) than in IHD patients with relatively quiescent symptoms. Abnormalities of blood clotting and platelet changes were not significantly altered by the presence of severity of coronary angiographic fixed obstruction in IHD. Multiple regression analysis indicated that hypercoagulability and increased platelet biologic activity were not a consequence of differences in risk factor patterns in IHD patients compared to control subjects.

Platelet synthesis of cyclooxygenase and lipoxygenase products in type I and type II diabetes

In 24 type I and 22 type II diabetic patients without vascular complications and in 25 controls platelet thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) production (by radioimmunoassay-RIA) and 1-14C arachidonic acid (AA) metabolism (by high pressure liquid chromatography-HPLC) after thrombin stimulation were studied. Platelets both from type I and type II diabetics generated larger amounts of TxB2 (p less than 0.001) and PGE2 (p less than 0.005) than controls, independently of the presence of retinopathy. No significant differences in platelet AA uptake or metabolism via the cyclooxygenase (CO) route, after thrombin stimulation (5 NIH U/ml), were observed in diabetic patients: lipoxygenase metabolites were found to be slightly, but significantly decreased. A positive linear relationship (r = 0.64, p less than 0.001) was found between HbA-1c and TxB2 production, but not with fasting plasma glucose. These results indicate that metabolic alterations can affect platelet function independently of vascular complications. The absence of alterations in intraplatelet 1-14C AA metabolism via CO, in the presence of increased TxB2 and PGE2 production from endogenous AA, suggests that the activation of CO is not the only possible mechanism of platelet activation and that probably an increased availability of platelet AA plays an important role in the enhanced platelet aggregation commonly found in diabetics.

Increased protein c and fibrinopeptide a concentration in patients with angina

Abstract Protein C and fibrinopeptide A (FpA) levels in plasma were measured in 30 controls and in two groups of patients with angina. The first group was formed by 27 patients suffering from spontaneous ischemic attacks (active angina).The second one was formed by patients who had previously suffered from angina, but were free from myocardial ischemic attacks for at least one month (inactive angina). Protein C (measured by electroimmunoassay ) and FpA (radioimmunoassay) were higher than controls in both groups but were significantly higher in patients with active angina than in patients with inactive angina. A clear trend toward a linear correlation existed between protein C and FpA levels , though it did not reach the statistical significance. These results confirm a significant involvement of blood clotting system in ischemic heart disease and specially in active angina.

Altered intraplatelet arachidonic acid metabolism during the acute state of unstable angina

Thromboxane A2 (TxA2) generation and 1-14C arachidonic acid (AA) metabolism by platelets (stimulated with thrombin) were studied in vitro in 16 patients with unstable angina both during the acute and chronic inactive phase of the angina. Eight patients with stable effort angina and 21 controls were also investigated. In acute unstable angina 1-14C AA metabolism was significantly increased through cyclooxygenase pathway resulting in a higher selective TxA2 generation than in stable effort angina and in controls (p less than 0.01). No differences were found between patients with stable effort angina and controls. The alterations in AA metabolism were no longer found when patients reverted to the inactive phase of angina. TxA2 generation by platelets was independent of the number of the daily ischemic attacks (r = 0.17, ns) in patients with unstable angina. Present results indicate that an altered intraplatelet AA metabolism leading to the increased TxA2 synthesis occurs simultaneously with the conversion of angina from the chronic to the acute phase.

Ticlopidine Activity on Platelet Function in Patients with Enhanced Platelet Aggregation

In a single-blind crossover study, the effect of ticlopidine (250 mg t.i.d.) on platelet function was investigated in 16 patients, with enhanced platelet aggregation, before treatment, on the third and seventh day of treatment with the drug or the placebo. Bleeding time was significantly lengthened by ticlopidine administration. Platelet aggregation, both in vivo and in vitro, was significantly inhibited during the week on ticlopidine. Beta-thromboglobulin concentration was on an average significantly decreased. The inhibition by PGI2 of platelet aggregation by PGD2 was slightly but not significantly increased. Platelet TxB2 production after stimulation with thrombin was unchanged during ticlopidine administration, whereas conversion of exogenous arachidonic acid into TxB2 was slightly but significantly reduced. The present results confirm that ticlopidine acts in vivo as a powerful antiaggregating agent. The antiaggregating activity seems to be due to an interference of ticlopidine with platelet membrane and, as a consequence, with various platelet membrane receptors and activities.