ADP-induced Platelet Aggregation In Patients Research Articles

Use of increased concentrations of adenosinediphosphate for high residual platelet reactivity in patients with coronary heart disease

Detection of a tendency to increased thrombosis in patients with coronary heart disease (CHD) is of important prognostic value in the selection of drugs aimed at achieving a persistent antithrombotic effect. The aim of the study was to evaluate the use of elevated ADP inducer concentrations to improve the accuracy of ADP-induced platelet aggregation in patients with coronary heart disease. Material and method. Material and method. We studied 48 patients with CHD who were on continuous double antiplatelet therapy for 6 months (aspirin 75mg and clopidogrel 75mg per day). The aggregation activity of the platelet suspension was studied using the Born method G. in the modification of Gabbasov Z. A. Platelet activity was evaluated by the degree of aggregation of platelet-rich plasma along the light transmission curve under the influence of the inducer adenosine diphosphate (ADP) at a concentration of 2 mmol/l and by its own patented method against the background of additional ADP application. Results. In patients, platelet aggregation decreased to 5-35% (p<0.005) compared to the standard values, which are 50-60%. The values of platelet aggregation with the additional introduction of the inducer of aggregation ADP in a ratio of 2:1 to 2 µmol/l for 1, 2, 3, and 4-minute registration of platelet aggregation, resulted in increased aggregation from 55% to 75% (p<0.001), indicating high residual platelet reactivity on the background of double antiplatelet therapy. Correlations of the degree of aggregation for elevated ADP concentrations with multivessel arterial lesion and dyslipidemia were also found, r=0.86 and r=0.92, respectively. Conclusion. The use of elevated concentrations of adenosine diphosphate in platelet aggregation in patients with ischemic heart disease increases the accuracy of assessing ADP-induced platelet aggregation against the background of dual antiplatelet therapy and contributes to the detection of high residual platelet reactivity.

ADP-induced platelet aggregation in patients with acute coronary syndrome treated with prasugrel or ticagrelor. Results of the ISAR REACT 5 platelet aggregation substudy

Abstract Introduction The recently published randomized multicenter open label ISAR REACT 5 trial showed that prasugrel was superior to ticagrelor with respect to the composite primary end point of death, myocardial infarction, or stroke at one year after randomization in patients with acute coronary syndrome with planned invasive evaluation. The reasons for this finding are speculative. Purpose The aim of this prespecified platelet aggregation substudy was to assess platelet aggregation induced by adenosine-diphosphate (ADP) in patients who received prasugrel or ticagrelor treatment and underwent PCI. Methods We assessed all patients who underwent PCI and who had valid ADP-induced platelet aggregation values at hospital admission and at 2–24 hours after administration of prasugrel or ticagrelor loading dose followed by maintenance dose. ADP-induced platelet aggregation values were measured using the Mulitplate Analyzer®. Patients were recruited in the German Heart Center, Munich, Germany or in Klinikum rechts der Isar, Munich, Germany, Technical University of Munich. Results A total of 608 patients were analyzed. Patients in the prasugrel group were slightly but significantly older than patients in the ticagrelor group (66,5 years versus 64,6 years, P=0,048). The remaining baseline characteristics did not significantly differ between the two treatment groups. ADP-induced platelet aggregation (median [IQR]) at baseline did not differ between prasgurel- and ticagrelor treated patients (809 [556; 1057] AU x min versus 797 [534–1095] AU x min. At 2–24 hours after study drug administration ADP-induced platelet aggregation was significantly lower in patients who had received prasugrel in comparison to ticagrelor (105 [57–176] AU x min versus 138 [77–207] AU x min (Figure 1). Conclusion ADP-induced platelet aggregation was significantly lower in patients who received prasugrel in comparison to patients who received ticagrelor, which could have influenced patients' outcome in the ISAR-REACT 5 trial. Figure 1 Funding Acknowledgement Type of funding source: None

256Heart transplant recipients with cardiac allograft vasculopathy have increased platelet aggregation before and after low-dose aspirin therapy

Abstract Background Following heart transplantation (HTx), long-term survival is reduced mainly due to development of a specific form of coronary artery disease, coronary allograft vasculopathy (CAV). Using optical coherence tomography to visualize the coronary artery wall, we have recently shown that layered fibrotic plaques resembling organized clots are the dominant plaque component in CAV. Thus, thrombosis is suggested as a possible mechanism contributing to development and progression of CAV. Aspirin is widely used after HTx despite limited evidence and lack of specific guidelines. The antiplatelet effect of aspirin has not been thoroughly examined in HTx-patients. Purpose To investigate baseline platelet aggregation and the antiplatelet effect of aspirin in HTx-patients with and without CAV. Methods We included 68 HTx-patients (median 8.6 years from HTx). In 66 patients taking 75 mg aspirin for a minimum of 7 days, platelet aggregation was measured in whole blood using impedance aggregometry with the following agonists: Adenosine diphosphate (ADP) stimulating ADP-receptors and arachidonic acid (AA) for monitoring of aspirin treatment. Aspirin compliance was confirmed by measuring serum-thromboxane B2. Platelet aggregation prior to aspirin therapy was measured in 59 patients as it was not considered clinically safe to interrupt ongoing aspirin treatment for one week prior to blood sampling in 9 patients mainly due to previous coronary stenting. CAV burden was determined by coronary angiography and echocardiography based on international classification. Patients were divided into two groups; no CAV (n=37) and CAV (n=29). Results In HTx-patients not treated with aspirin, we found significantly increased ADP-induced platelet aggregation in patients with CAV vs. patients without CAV (904 (95% CI 813–995) vs. 786 (95% CI 728–843) AU*min, P=0.02). Baseline AA-induced aggregation was also higher in patients with CAV vs. patients without CAV, though non-significant (994 (95% CI 907–1081) vs. 905 (95% CI 839–972) AU*min, P=0.10). Even though aspirin reduced AA-induced platelet aggregation in both groups, patients with CAV had significantly increased AA-induced platelet aggregation compared with patients without CAV on aspirin treatment (380 (95% CI 295–465) vs. 286 (95% CI 239–334) AU*min, P=0.04) (Fig. 1). Conclusions HTx-patients with CAV have increased platelet aggregation before and after aspirin treatment compared with HTx-patients without CAV. Aspirin monotherapy may not provide sufficient platelet inhibition in HTx-patients with CAV. Acknowledgement/Funding Aarhus University (PhD-salary)

The effects of prolactin on ADP-induced platelet aggregation in patients with stable angina of effort and gastroesophageal reflux disease

The combination of stable angina of effort (SEA) and gastroesophageal reflux disease (GERD) is frequently observed in the clinic of internal diseases. Thrombocytic link of homeostasis is one of the main factors in the development and progression of atherosclerosis. The long-term increase of circulation prolactin levels can result in the development of pathological changes caused by hyperprolactinemia.Objective — to investigate the effect of prolactin levels on the ADP-induced platelet aggregation in patients with SEA and GERD.Materials and methods. The study included 148 persons: 30 patients with isolated SEA (1st group), 30 patients with isolated GERD (2nd group), and 88 patients with combination of SEA and GERD (3rd group). A separate group consisted of 20 practically healthy persons (PHPs). The serum levels of prolactin and the degree, rate, and time of ADP-induced platelet aggregation were investigated in all patients, included in the study.Results and discussion. The degree, rate, time of ADP­induced platelet aggregation, as well as prolactin levels, were significantly higher in patients with SEA and comorbidity of GERD than the similar results of the PHPs group, patients with isolated SEA and isolated GERD. A high direct correlation relationship was established between the degree of ADP-induced aggregation of blood platelets in patients with SEA with comorbid GERD and serum prolactin levels (r = 0.710; r = 0.696). Conclusions. It has been established that in patients with SEA with comorbid GERD, the prolactin levels were higher than in groups with isolated SEA, isolated SEA and PHPs group and increaseв proportionally to the degree and rate of ADP-induced platelet aggregation.

Indicators of ADP-induced platelet aggregation in patients with hypertension complicated by ischemic hemisphere stroke

Arterial hypertension is one of the most significant factor in the development of cardio-vascular complications in patients due to elevated blood pressure, maintenance of disorders of endothelial function and coagulation system, as well as changes in platelets function. The purpose of the work was to determine the characteristics of ADP-induced platelet aggregation in hypertension patients with ischemic hemisphere stroke. Material and methods. The enrolled patients (n =152) were divided into 3 groups. The first one included 38 patients (an average age of 64 [57−72] years, (male 35%)) with arterial hypertension (AH) who reached the target level of blood pressure (according to the «office» measurements and ambulatory blood pressure monitoring). The second group included 96 AH patients aged 60 [64−71] years, (62% men) who did not reach the target level of blood pressure. And the third group involved 18 patients aged 66 [66−72] years (male 56%) with AH complicated by ischemic hemisphere stroke. Platelet aggregation was performed using light transmittance aggregation by optical analyzer (Solar, R.B.) with adenosine 5'-diphosphate (Sigma-Aldrich) at final concentration of 10.0 × 10 6 mol / L. Results . There were significantly higher rates in hypertensive patients with ischemic hemisphere stroke of the maximum degree of platelet aggregation in 10 minutes (T max, 10min ) by 18 % (78 [78−100] % vs. 66 [57−83] %, respectively, U = 554.0; p = 0.015), the maximum aggregation time (t Tmax, 10min ) by 34 % (78 [78−100] s vs. 66 [57−83] s, respectively, U = 554.0, p = 0.015). The degree of platelet aggregation at the end of the recording time (T 10min ) and the area under the curve of the end of the 10 min. (AUC 10min ), respectively, by 19.4 % and 15 % than in AH patients who have not reached the target level of blood pressure. Conclusions . Hypertensive patients who did and did not reach the target level of blood pressure showed no significant difference in analyzed parameters of ADP-induced platelet aggregation. However, there was approximately twofold increase in deaggregation (K desagg, 10min ) among patients who did not reach the target level of blood pressure compared with those who reached it. Meanwhile, hypertensive individuals with ischemic hemisphere stroke had significantly higher ADP−induced aggregation parametrs as percentage of aggregation during 10 min. (T 10min ), the area under the aggregation curve at the end of 5th (AUC 5 min ) and 10th min. (AUC 10min ) in comparison to hypertensives who did not reach the target blood pressure level. The influence of drugs on the studied parameters of ADP-induced platelet aggregation in patients is not established.

Features of ADP-induced platelet aggregation in patients with community-acquired pneumonia 3-d group and its changes during treatment

Introduction. Especially dangerous are forecast of hemorrhagic complications of pneumonia. Therefore, the study of aggregation properties of platelets in patients with community acquired pneumonia third group is the most important task of modern pulmonology.Aim of this work was studying of the features of ADP-induced platelet aggregation in patients with community acquired pneumonia third group.Material and methods. In an open prospective study included 50 patients with community acquired pneumonia the third group and 30 healthy individuals. The functional activity of platelets analyzed by the method of Born on platelet aggregation analyzer AR 2110 «SOLAR» (Belarus). As an inducer of aggregation used bacterial 5'-adenosine disodium salt dyphosphorus acid («Sigma Aldrich», USA) in a final concentration of 5 mM/l.Results. In patients with community acquired pneumonia 3-d group compared to the practically healthy individuals revealed a significant degree of inhibition of ADP-induced platelet aggregation by 37% (p<0.05). Also there was likely reduce the time of ADP-induced platelet aggregation at 46.7% (p<0.05). The rate of ADP-induced platelet aggregation in patients with community acquired pneumonia tended to decrease with 54.01±2.68% / min. to 46.00±3.99% / min. and almost reached the limits of statistical probability (p=0.057). Under the influence of treatment there was a further significant decrease only the degree of ADP-induced platelet aggregation by 12.5% (p<0.05). Indicators of time and rate of aggregation were not significantly changed.Conclusions. In patients with community acquired pneumonia 3-d group observed decrease of degree and time of ADP-induced platelet aggregation. There is a further decrease of the degree of ADP-induced aggregation during treatment, without significant alteration of speed and time aggregation.

Intensive atorvastatin improves endothelial function and decreases ADP-induced platelet aggregation in patients with STEMI undergoing primary PCI: A single-center randomized controlled trial

BackgroundIntensive atorvastatin may be beneficial for patients with ST segment elevated myocardial infarction (STEMI). However, its effects on endothelial and residual platelet function remain uninvestigated in these patients. MethodsThis single-center single-blinded prospective randomized controlled trial included STEMI patients undergoing PCI, aiming to investigate the acute effects of intensive atorvastatin (40mg) vs. standard atorvastatin (20mg) on serum endothelin-1 (ET-1) and ADP-induced platelet clot strength (MA-ADP), which were measured before and after 7days of atorvastatin treatment respectively. MA-ADP was measured by thromboelastography. The tolerance and safety of intensive atorvastatin therapy in these patients were also observed. ResultsA total of 120 patients (60 patients in the intensive group and 60 patients in the standard group) with STEMI, who are undergoing primary PCI, were included into this study (mean age, 63.5years). Patients from these two groups were matched for baseline characteristics. Atorvastatin did not significantly affect the serum level of LDL-C or CRP in either the standard or intensive group. Furthermore, ET-1 did not significantly change following treatment with atorvastatin in the standard group. However, intensive treatment with atorvastatin significantly reduced ET-1 serum level (0.65±0.38pmol/L vs. 0.49±0.21pmol/L, P<0.05) and achieved a greater reduction of MA-ADP (49.2±12.1 vs. 38.4±17.4mm, P<0.05). In addition, although not statistically significant, patients assigned to the intensive group appeared to suffer from less major adverse cardiovascular events. ConclusionsPeriprocedural intensive atorvastatin is associated with improved endothelial function and platelet inhibition, and is well-tolerated in STEMI patients undergoing PCI.

Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.

Dabigatran and rivaroxaban are novel, vitamin K-independent oral anticoagulants (NOACs) and act via antagonism of the coagulation factor (F) IIa (dabigatran) or FXa (rivaroxaban), respectively. Compared to vitamin-K-antagonists, NOACs have shown non-inferiority of risk and benefit in patients with non valvular atrial fibrillation (AF). In clinical practice there is increasing use of NOACs combined with platelet inhibitors in patients with AF and coronary artery disease. However, whether NOACs affect the function of platelet inhibitors remains incompletely known. This observational study aimed to assess the platelet function in patients receiving dabigatran or rivaroxaban and concomitant platelet inhibitors. A single centre observational study was performed analysing the platelet aggregation of patients treated with dabigatran or rivaroxaban with or without concomitant platelet inhibitors. Measurements before the initiation of NOAC therapy served as the respective control group. Platelet aggregation was measured by multiple electrode aggregometry and was induced with adenosine diphosphate (ADP, 6.5µM) and arachidonic acid (AA, 0.5mM), respectively. In order to evaluate whether NOACs interact with platelet inhibition by ASA or the P2Y12-antagonist clopidogrel, 87 patients were grouped according to their concomitant antiplatelet medication. Comparing the ADP- and AA-induced platelet aggregation in patients without concomitant platelet inhibitors (n=45) no significant differences under therapy with dabigatran (d) or rivaroxaban (r) compared to the control group (c) were observed. In patients taking clopidogrel as a concomitant platelet inhibitor (n=21), neither dabigatran nor rivaroxaban affected the ADP-induced platelet aggregation (c 20±11, d 21±14, r 18±8 AU*min, p=0.200). Patients receiving dabigatran or rivaroxaban in combination with ASA (n=42; 21 ASA only, 21 ASA+clopidogrel) showed no significant differences of the AA-induced aggregation compared to the control group (c 10±8, d 9±7, r 10±8 AU*min, p=0.810). The antiplatelet effects of ASA and clopidogrel monitored by AA- or ADP-induced platelet aggregation were not affected by NOAC therapy.

Effect of statins on platelet function in patients with hyperlipidemia

IntroductionIt is generally assumed that cholesterol reduction by statins is the predominant therapeutic result underlying their beneficial effects in cardiovascular disease. However, the action of statins may be partially independent of their effects on plasma cholesterol levels, as they combine lipid lowering with positive effects on hemorheological conditions and endothelial function. We evaluated the impact of statin treatment on platelet adhesion to fibrinogen (spontaneous and ADP-activated), along with ADP, collagen or ristocetin-induced aggregation in type II hyperlipidemic patients.Material and methodsThe study group included 70 persons: 50 patients affected by type II hyperlipidemia without concomitant diseases and 20 healthy volunteers. The effects of 8-week statin treatment (atorvastatin 10 mg/day, simvastatin 20 mg/day, or pravastatin 20 mg/day) on platelet activation were evaluated.ResultsRegardless of the type of statin, a significant decrease in ADP-induced platelet aggregation was observed: for atorvastatin 50.6 ±12.8% vs. 41.1 ±15.8% (p < 0.05), for simvastatin 57.2 ±18.0% vs. 44.7 ±22.1% (p = 0.05), and for pravastatin 55.8 ±19.5% vs. 38.8 ±23.3% (p < 0.05). There was no significant effect of statins on collagen or ristocetin-induced platelet aggregation and adhesion.ConclusionsTherapy with statins beneficially modifies ADP-induced platelet aggregation in patients with hyperlipidemia and does not affect spontaneous or ADP-induced platelet adhesion to fibrinogen and platelet aggregation induced by collagen or ristocetin.

Analysing responses to aspirin and clopidogrel by measuring platelet thrombus formation under arterial flow conditions

High residual platelet aggregability and circulating platelet-monocyte aggregates in patients administered aspirin and clopidogrel are associated with ischaemic vascular events. To determine the relevance of these factors with residual thrombogenicity, we measured platelet thrombus formation using a microchip-based flow-chamber system in cardiac patients receiving aspirin and/or clopidogrel, and evaluated its correlation with agonist-inducible platelet aggregation and platelet-monocyte aggregates. Platelet thrombus formation was analysed by measuring flow pressure changes due to the occlusion of micro-capillaries and was quantified by calculating AUC 10 (area under the flow pressure curve. The growth and stability of platelet thrombi that formed inside microchips at shear rates of 1000, 1500, and 2000 s⁻¹ were markedly reduced in patients receiving aspirin and/or thienopyridine compared to healthy controls (n=33). AUC 10 values of aspirin therapy patients (n=20) were significantly lower and higher than those of healthy controls and dual antiplatelet therapy patients (n=19), respectively, and showed relatively good correlations with collagen-induced platelet aggregation and platelet-monocyte aggregates at 1000 and 1500 s⁻¹ (rs >0.59, p<0.01). In contrast, AUC 10 in dual antiplatelet therapy patients was significantly correlated with ADP-induced platelet aggregation at all examined shear rates (rs >0.59, p<0.01), but did not correlate with collagen-induced aggregation. Aspirin monotherapy patients with high residual platelet thrombogenicity also exhibited significant elevations in both collagen-induced platelet aggregation and platelet-monocyte aggregates. Our results, although preliminary, suggest that residual platelet thrombogenicity in aspirin-treated patients is associated with either collagen-induced platelet aggregation or circulating platelet-monocyte aggregates, but it is predominantly dependent on ADP-induced platelet aggregation in patients receiving dual antiplatelet therapy.

The influence of bisoprolol dose on ADP-induced platelet aggregability in patients on dual antiplatelet therapy

Dual antiplatelet therapy is recommended after acute coronary syndrome or after percutaneous coronary intervention with coronary stent implantation. Many of the patients on dual antiplatelet therapy receive β-blockers; some of them could have antiaggregatory effect. Bisoprolol is a highly selective adrenoceptor-blocker, which is often used in the settings of percutaneous coronary intervention or acute coronary syndrome in patients on dual antiplatelet therapy. Its antiaggregative effect has not been extensively studied. Therefore, the aim of this study is to investigate the effect of bisoprolol on ADP-induced platelet aggregation in patients on dual antiplatelet therapy. Platelet aggregability has been measured in 100 patients on dual antiplatelet therapy with multiplate analyzer using ADP test in blood samples anticoagulated with heparin. ADP test values have been expressed by arbitrary units/minute. In univariate and multivariate regression analyses, we have investigated the influence of bisoprolol and its dose and also different factors, such as risk factors, concomitant drugs and their dosage, laboratory findings, on ADP test values. Univariate regression analysis showed significant correlation between the bisoprolol dose and the ADP test value (P=0.046, B=52.55, 95% confidence interval 0.87-104.23), which was also shown in the multivariate regression analysis (P=0.018; B=57.011; 95% confidence interval 10.455-103.567). We have identified a positive correlation between bisoprolol dose and ADP-induced platelet aggregability in patients on dual antiplatelet therapy.

Association between inflammatory biomarkers and platelet aggregation in patients under chronic clopidogrel treatment

Inflammatory processes in the vessel wall are associated with progression of atherosclerosis and myocardial infarction. Both high levels of C-reactive protein (CRP)and high on-clopidogrel treatment platelet reactivity (HPR) have been linked to an increased risk of ischaemic events after percutaneous coronary intervention (PCI). The aim of this study was to explore the association between biomarker levels of inflammation and platelet reactivity. Stable patients (n=1,223) eligible for this study were under chronic antiplatelet treatment with aspirin and clopidogrel due to prior coronary stent placement. ADP-induced platelet aggregation (in AU*min) was measured on a Multiplate analyser. The primary outcome measure of this retrospective study was the ADP-induced platelet aggregation in patients with versus those without elevated CRP levels. Of the patients 15.5% (n=189) showed elevated CRP levels (≥5 mg/l). Platelet aggregation (median [interquartile range]) was significantly higher in patients with elevated CRP levels compared to patients with normal (<5 mg/l) CRP levels (305 [202-504] AU*min vs. 218 [144-384] AU*min; p<0.001).A multivariable linear regression model that adjusted for known predictors of HPR confirmed a significant independent association between elevated CRP levels and high ADP-induced platelet aggregation values (p=0.0002).Elevated WBC count and fibrinogen levels were also associated with higher platelet aggregation values (p<0.001 for both). In conclusion, elevated levels of CRP, WBC count and fibrinogen were significantly associated with high platelet reactivity in patients under chronic clopidogrel treatment. Whether a direct relation between platelets and inflammation exists, as well as the clinical impact of our results, warrants further investigations.

Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3

The platelet P2Y12 receptor is the target of clopidogrel therapy, which has been shown to reduce thromboembolic complications of atherosclerotic disease but has limitations in terms of variability of response and irreversibility of effect. This receptor is also a target for ticagrelor (AZD6140), the first reversibly binding oral P2Y12 receptor antagonist that does not require metabolic activation and yields more consistent inhibition of platelet aggregation than clopidogrel therapy. Single nucleotide polymorphisms (SNPs) have been described in the gene for this receptor (P2RY12), some of which have been associated with variability in platelet reactivity. SNPs in P2RY1 and ITGB3 have also been reported by some groups to affect platelet reactivity to adenosine diphosphate (ADP). We assessed whether SNPs in these genes influenced the pharmacodynamic response to ticagrelor in patients enrolled in both the DISPERSE study (stable atherosclerotic disease) and the DISPERSE2 study (non-ST-segment elevation acute coronary syndromes). Platelet aggregation data (at baseline and 4 weeks) and DNA samples from clopidogrel-naive Caucasian patients treated with ticagrelor were available for 151 patients. Seventy four SNPs within three genes were genotyped. After adjustment for multiple comparisons, none of these SNPs were found to significantly influence inhibition of ADP-induced platelet aggregation by ticagrelor.

Effects of omega-3 fatty acid on platelet serotonin responsivity in patients with schizophrenia

Studies suggest that the omega-3 fatty acid supplementation may be beneficial in reducing symptom severity in schizophrenia. The mechanism(s) underlying the clinical effect is not known. Serotonin (5-HT) has been implicated in the pathophysiology of schizophrenia and in the mechanism of some antipsychotic agents. 5-HT receptors are known to be modified by omega-3 fatty acids. We examined whether supplementation with the omega-3 fatty acid eicosapentaenoic acid (EPA)-modified 5-HT amplified ADP-induced platelet aggregation in patients with schizophrenia. Two grams of ethyl-EPA was administered daily for 6 months supplementally to ongoing antipsychotic treatment in 12 patients with chronic schizophrenia, using an open-label design. Red blood cell membrane fatty acids and platelet functions (platelet aggregation and dense granule secretion) were monitored at baseline, 1-, 3- and 6-months. The EPA levels were elevated more than five-fold in RBC membranes of all patients after 3 months supplementation, indicating a high degree of compliance. Consistent with previous reports, there was inhibition of ADP-induced platelet aggregation by EPA supplementation. Moreover, EPA markedly enhanced the 5-HT responsivity as measured by the magnitude of 5-HT amplification on ADP-induced platelet aggregation. Previously, we have demonstrated a significant inverse correlation between 5-HT responsivity and psychosis severity in unmedicated patients with schizophrenia. Taken together, the present data support the notion that EPA may be mediating its therapeutic effects in schizophrenia via modulation of the 5-HT 2 receptor complex.

Antiplatelet Therapy Following Cardiac Valve Replacement—A Comparative Study of Aspirin and Ticlopidine

The antiplatelet agents, aspirin and ticlopidine, are widely used to prevent thromboembolism following cardiac valve replacement. To compare the clinical effects of each platelet inhibitor, a daily dose of ticlopidine 300 mg was given to 50 patients who underwent aortic valve or mitral valve replacement with an average age of 56.9 years over a mean 52.6 months after surgery. 50 more patients with an average age of 50.2 years were given a daily dose of aspirin 81 mg over a mean 51.3 months after surgery. Warfarin was given to maintain thrombotest values at 10 to 25% (PT-INR at 1.6-3.0). The incidence of thromboembolism was low in both groups; 1.0/100 patient years in the ticlopidine group and 1.9 in the aspirin group. Hemorrhagic complications, hematuria and ecchymosis, showed an incidence of 2.9 in the ticlopidine group and 2.3 in the aspirin group. Slight increases in GOT and GTP were observed in 4 and 18% of cases and elevated total cholesterol and neutral fat in 2 and 18% of cases. No adverse reactions were reported. With the exception of a significant decrease in ADP-induced platelet aggregation in patients who took ticlopidine, there were no significant differences observed between the two groups.

A lack of effect of captopril on platelet aggregation in patients with congestive heart failure

We have studied the acute and chronic effects of an ACE inhibitor (captopril) on platelet function and the renin-angiotensin system in patients with congestive heart failure. Plasma concentrations of angiotensin II fell significantly after a single dose of captopril (25 mg) and during long-term treatment with captopril (2 weeks, 75 mg/day). Plasma renin activity increased significantly after both the single and repeated doses. Captopril did not affect ADP-induced platelet aggregation or concentrations. It seems unlikely that circulating angiotensin II affects ADP-induced platelet aggregation in patients with congestive heart failure.

Heparin-enhanced ADP-induced platelet aggregation in patients undergoing cardiopulmonary bypass surgery

Heparin has been shown to enhance ADP-induced platelet aggregation in patients undergoing cardiopulmonary bypass surgery. This effect appears to be maximal throughout the initial 30 minutes of systemic heparinization and once reached is maintained throughout the bypass procedure. The prebypass state is regained following heparin reversal by protamine sulphate. It is possible that this effect of heparin on platelet function may contribute towards some of the platelet microembolization phenomena seen in patients following cardiopulmonary bypass surgery.