Thrombocyte Aggregation Research Articles

Hyperhomocysteinemia--a risk factor for development of occlusive vascular diseases

Occlusive vascular diseases take the first places on lists of diseases in general population today. In spite of this, all risk factors which contribute to development of these diseases are not yet known. Recent studies have shown that homocysteine plays a critical role in it and is established as a new risk factor. WHAT IS HOMOCYSTEINE?: Homocysteine is a sulfur containing amino acid formed in the metabolism of methionine. Reference values of homocysteine in circulation and different forms in plasma are described. HYPERHOMOCYSTEINEMIA--A RISK FACTOR: Homocysteine was associated with atherosclerosis and occlusive vascular disease in 1960s for the first time. Since then, many studies--prospective and retrospective, have confirmed the role of hyperhomocysteinemia as a risk factor in 42% of patients with cerebrovascular disease, 28% with peripheral vascular and 30% with coronary artery disease. The Physician's Health Study, a prospective study in which 15,000 male physicians took part, revealed that increase in homocysteine concentration of 1.7 mumol/l above normal values was associated by threefold higher risk for myocardial infarction. The risk for carotid artery stenosis also increases with elevation of homocysteine concentration. Hyperhomocysteinemia is associated with poor prognosis in patients with angiographically established coronary disease. Stroke, venous thromboembolism, and atherosclerosis in chronic renal failure are some of the complications of hyperhomocysteinemia. Hyperhomocysteinemia has numerous genetic and nongenetic etiologic factors. Cystathionine synthase deficiency, methylenetetrahydrofolate reductase deficiency and defects in the synthesis of cobalamin cofactors are genetically determined. Nutritional factors such as B12, folate or B6 vitamin deficiency, cofactors in homocysteine metabolism, lead to hyperhomocysteinemia. Atherogenic propensity of homocysteine is related to endothelial dysfunction, blood thrombocyte aggregation changes in factors of coagulation. Oxidative stress is involved, but the exact mechanism is still unknown. Hyperhomocysteinemia is established as an important risk factor for occlusive vascular diseases. Reduction in homocysteine concentration can be achieved by supplementation of B-group vitamins, cofactors in homocysteione metabolism. Is it going to be effective in reducing cardiovascular risks remains to be seen.

Application of cationic propyl gallate as inducer of thrombocyte aggregation for evaluation of effectiveness of antiaggregation therapy.

Acetylsalicylic acid (ASA) is one of basic preparations used in the therapy of cardiovascular diseases. Application of ASA leads to irreversible reduction of platelet aggregation. The aim of the present study was to verify monitoring of effectiveness of ASA therapy using the measurement of platelet aggregability in vitro after induction by cationic propyl gallate (CPG), which is considered to be a highly potent inducer of aggregation. We examined a group of 27 healthy volunteers, divided into two subgroups (n = 19, n = 8). The first subgroup was examined for thrombocyte aggregation before and 24 hours after administration of 400 mg of ASA after induction by ADP, collagen, adrenalin and CPG. The second subgroup was examined for thrombocyte aggregation before and after a three-day administration of ASA in a dose of 100 mg/day. In the group of 27 healthy volunteers we determined normal values of aggregability for individual inducers. Low stability of the used methods was proved (weak or insignificant correlation of results of the same method before and after administration of ASA). The most advantageous parameter for monitoring of effectiveness of 400 and 100 mg of ASA was CPG slope (paired t test, p < 0.00000002, resp. p < 0.001). The parameter of CPG slope we determined in both subgroups the cut-off value (< 53s), by means of which it is possible to discriminate probands according to ASA therapy (in contrast to other routinely used inducers). The obtained results indicate that measurement of thrombocyte aggregation after CPG induction reveals a significantly lower percentage of ASA non-responders ASA than after other inducers. Measurement of thrombocyte aggregation after CPG induction is predicted to be highly promising for monitoring the effectiveness of anti-aggregation therapy.

Heparin-induced priapism

Heparin-induced priapism constitutes a special form of pharmaco-induced prolonged erection, but the pathophysiological principles are not yet definitely clear. Heparin-induced antiplatelet-antibodies may lead to the aggregation of thrombocytes and thus alter the penile blood flow leading to low-flow priapism. Alternatively, this condition may be explained by initial high-flow priapism that later turns into ischemic priapism. The question remains whether hemorrhage with subsequent organisation of the hematoma and late fibrosis constitutes a pathogenetic factor. Besides this pathogenetic discussion, this paper presents the differential diagnosis of priapism as well as diagnostic and therapeutic procedures.

Secondary prevention with fluvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein

Background: Treatment of hypercholesterolaemia with HMG-CoA reductase inhibitors results in an earlier reduction of morbidity and mortality than expected from trials using conventional cholesterol-lowering therapies. Possible explanations for this effect include stimulation of angiogenesis, improvement of endothelial function, plaque stabilisation, inhibition of coagulation and/or thrombocyte aggregation and inhibition of the inflammatory response associated with atherosclerosis. Methods: We investigated whether statins exert their effects by inhibition of endothelial activation, inflammation and/or monocyte/macrophage activation by measuring plasma levels of soluble cell adhesion molecules, neopterin and C-reactive protein upon treatment with fluvastatin for a period of 12 months in patients with established atherosclerosis and hypercholesterolaemia. Results: Blood samples were taken at baseline and at 3 and 12 months after starting treatment with fluvastatin 80 mg daily. Upon treatment, a reduction of s-ICAM-1 (956.3±123.6 vs. 745.4±127.4 vs. 674.9±70.8 ng/ml, P<0.05) and s-E-selectin (58.6±6.7 vs. 47.0±6.1 vs. 44.9±3.2 ng/ml, P<0.01) was observed. In addition, levels of neopterin decreased, albeit transiently (7.1±0.7 vs. 6.0±0.5 vs. 6.5±0.8 nmol/l, P=0.02), suggesting a reduction in monocyte/macrophage activity. Moreover, we found a decrease in levels of C-reactive protein during follow-up (5.21±2.0 vs. 3.18±0.7 vs. 1.95±0.3 mg/l, P<0.05), compatible with a reduction in inflammatory activity. Conclusion: We conclude that statins have a combined beneficial effect on monocyte/macrophage activity, endothelial function and systemic inflammatory activity.

Hemostasis in children with dysbacteriosis in chronic constipation.

The purpose of the study was to investigate hemostasis in children with dysbacteriosis disturbance in chronic constipation. The disturbance of factors in the inner mechanism of blood coagulation (VII, IX, XI, XII) in compensated chronic constipation was defined based on the reduction in colon bacillus levels. We observed hypocoagulation caused by the reduced activity of the prothrombin complex factors, disaggregate thrombocytopathy, and endotheliosis with fibrinolysis inhibition in subcompensated chronic colostasis with continuous reduction of colon bacillus levels and pathogenic microflora appearance. In decompensated colostasis there was an increase in pathogenic microorganisms and a continuous reduction of colon bacillus levels. In hemostasis there was a factor deficiency in inner (XII, XI, IX, VIII) and outer (II, V, VII, X) blood coagulation mechanisms. Fibrinolysis inhibition, endotheliosis development with thrombocyte aggregation, and microthrombosis formation were determined. Thus, in children with chronic constipation, there was a marked reduction in the amount of colon bacillus, which led to the reproduction of pathogenic bacteria. We also observed chronometric hypocoagulation with the inner (XII, XI, IX, VIII) and outer (II, V, VII, X) mechanisms of blood coagulation, at the base of which there is the deficiency of vitamin K-dependent factors (II, VII, IX, X) and a slightly marked disturbance in the final stage of coagulation. In thrombocyte vascular hemostasis, thrombocytopathy was observed with increased adenosine-5-diphosphate aggregation and the inhibition of the inner mechanism with fibrinolysis and endotheliosis.

Beta-lactam derivatives as enzyme inhibitors: carboxy peptidyl derivatives of (S)-4-oxoazetidine-2-carboxylate as peptidomimetics.

4-Oxoazetidine-2-carboxylic acid, protected at the nitrogen by silyl groups, was coupled with amino acid and oligopeptide esters. Desilylation and deprotection of the amino acid residues yielded the free beta-lactam peptides. Structure and properties were elucidated by spectroscopic methods and discussed. Some selected compounds were tested as fibrinogen inhibitors and for thrombocyte aggregation. None of the compounds showed any activity up to a concentration of 10(-5) Mol/l. Some other compounds exhibited a weak inhibitory activity against elastase (PPE).

Alcohol and the risk of myocardial infarction.

Epidemiological studies have repeatedly demonstrated a beneficial effect of moderate alcohol consumption on the incidence of coronary heart disease, myocardial infarction and overall mortality. The latter increases with excessive alcohol consumption. Although most epidemiological studies demonstrate a beneficial effect of alcohol consumption independent from the specific kind of alcoholic beverage, there is increasing evidence that wine and in particular red wine might contain pharmacological substances, which prevent atherosclerosis and myocardial infarction independent from the wine ethanol. Pathophysiological mechanisms mediating these beneficial effects include effects of wine phenols and tannins on LDL-cholesterol oxidation status, thrombocyte aggregation, endothelial function and smooth muscle cell proliferation. Identification and characterization of the pharmacologically active substances might provide the stage for the development of new substances to be used in the prevention of coronary artery disease and myocardial infarction.

Haemocompatibility of endovascular coronary stents: Wiktor GX.

The stent to be examined (Wiktor-Stent, Medtronic ESTC, Kerkrade, NL) was mounted into a closed-loop tubular-system and perfused with platelet-rich plasma (PRP). As controls the tubular-system without stent (as non-thrombogenic control) and secondly the tube filled with glassbeads (as thrombogenic control) were evaluated. A decrease in the number of singularly circulating thrombocytes correlated well with an increases in circulating platelet aggregates. The increasing activation of thrombocytes was demonstrated by immunolabelling of surface structures (CD 62) which become prominent on activation of thrombocytes. The increase in case of the non-thrombogenic controls is thought to be due to the action of the roller-pump. This increase was coincident with an increase in immunologically labelled GPIIb/IIIa receptors and well correlated with an increase in platelet activation as demonstrated by the elevated CD 62 label. In spite of the use of anticoagulation principles in the perfusion model, thrombin was generated (measured by the TAT-complex) in all three cases and the completed coagulation (measured by the occurrence of fibrin D-dimers) also happened. The amount of D-dimers was small, however, in the cases of non-thrombogenic controls and of tubes equipped with stents. Only after the contact of PRP with tubes filled with glass-beads a significant increase in D-dimers followed. In conclusion the implantation of a stent led to an activation, adherence and aggregation of thrombocytes to a somewhat greater extent as in the control-system. It has, however, a much less thrombogenic surface than glass-beads.

Lymphocyte-Neutrophilic Granulocyte Aggregates With and Without Associated Spurious Leukopenia in Beagle Dogs

Three cases are reported of male Beagle dogs which initially showed indications for clumped cells on the scattergrams of a haematology analyser with automated ‘5-part’ white blood cell, WBC, differentiation using potassium EDTA anticoagulated blood. On analysis of the bloodsmears leucocyte aggregates were observed consisting of lymphocytes and neutrophilic granulocytes in ratios varying from 1:1.1 to 1:1.9. The aggregates differed in size from 5 to 10 cells. In aggregates, occasionally eosinophilic granulocytes were present but no thrombocytes. In two cases thrombocyte aggregates with leucocytes on the surface (‘inverted’ rosettes) were observed with sodium citrate and lithium heparin anticoagulated blood samples. In one case the leucocyte agglutination seems to be of spontaneous origin because the aggregates were present in the predosing analysis and after placebo treatment. In the other two cases the aggregates arose during the treatment with an experimental medicine. In two cases spurious leukopenia was observed associated with the leucocyte aggregates but in the other case the quantity and distribution over the various classes of white blood cells appeared unchanged. Methodology experiments indicated that the formation of the aggregates were temperature- and EDTA-dependent effects on the leucocyte membrane factors, possibly aided by serum globulins.

Predictors for prophylactic antithrombotic prescribing in ischaemic heart disease and the impact of national guidelines.

Assessment of predictors for initiating prophylactic antithrombotic prescribing for patients newly diagnosed with ischaemic heart disease (IHD) and the impact of the introduction of national guidelines. A retrospective case-control study was performed using pharmacy prescription data from 120,000 Dutch patients over a 5-year period. IHD patients were identified using as a marker multiple nitrate prescriptions [anatomical-chemical-therapeutic (ATC) code CO1D] indicating chronic use. Initiation of antithrombotic therapy was likewise identified using ATC codes B01AA and B01AC (oral anticoagulants and thrombocyte aggregation inhibitors), prescribed within 6 months following the first nitrate prescription. Statistically significant (P<0.05) predictors were assessed using multivariable analysis considering patient, prescriber and medication characteristics. Of the 2598 patients who met specified inclusion criteria for newly diagnosed IHD, approximately 35% was not prescribed any type of antithrombotic therapy. Male patients [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.0-2.9], patients with cardiovascular (other than IHD) and diabetic co-morbidity (OR 6.4, 95% CI 4.8-7.9 and OR 1.6, 95% CI 1.1-2.1, respectively) and patients using isosorbide mononitrate rather than isosorbide dinitrate as anti-ischaemic main therapy (OR 2.1, 95% CI 1.3-2.5) were most likely to be prescribed antithrombotic therapy. Furthermore, initiating antithrombotic prescribing was more likely after the introduction of national guidelines (OR 1.4, 95% CI 1.1-1.7). Initiating antithrombotic prescribing in newly diagnosed IHD patients can be predicted by patient gender, certain co-morbidity and main type of nitrate therapy. The introduction of national guidelines has resulted in an increase of prophylactic antithrombotic prescribing in accordance with their contents.

ESSENTIAL FATTY ACID METABOLISM IN THE MICROPREMIE

Lipids are structural components of all tissues and are indispensable for cell membrane synthesis. The brain, retina, and other neural tissues are particularly rich in LCPUFAs, affecting neural structural development and function. LCPUFAs serve also as specific precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes, and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions, and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, uterine contraction). Dietary lipid intake affects cholesterol metabolism at an early age and is associated with cardiovascular morbidity and mortality in later life. Over recent years, the role of fatty acids in modulating signal transduction and regulating gene expression have been described, emphasizing the complex of fatty acid effects. Dietary fatty acids, especially LCPUFA, can have significant effects in the modulation of developmental processes affecting the clinical outcomes of extremely premature infants.

Glycoprotein IIIa Pl(A) polymorphism associates with progression of coronary artery disease and with myocardial infarction in an autopsy series of middle-aged men who died suddenly.

Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl(A1/A2) polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the Pl(A) polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (P=0.01) between the Pl(A2)-positive genotype and coronary artery stenosis. The frequency of possessing the Pl(A2) allele was significantly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with >50% coronary stenosis (18.3%) than among those with <25% stenosis (32.9%). Although the Pl(A) polymorphism was not directly associated with MI, the Pl(A2) allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In line with this result, men possessing the Pl(A2) allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (P<0.05). The present results suggest that the Pl(A) polymorphism is involved in the development of CAD and MI. Men with the Pl(A2) allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the Pl(A1) allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis.

Essential fatty acids as determinants of lipid requirements in infants, children and adults.

Essential fatty acids (EFA) are the indispensable component of the lipid supply beyond the provision of energy as a fuel for oxidation. They serve as dietary precursors for the formation of prostanoids and other eicosanoids thus are of great significance in health and modulation of disease conditions. Eicosanoids are powerful autocrine and paracrine regulators of cell and tissue functions: thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, and uterine contraction. Recent attention has focused on the effect of n-3 and n-6 long chain EFAs in normal fetal development. Results from human infant studies suggest that n-3 fatty acids are needed for optimal development of visual and brain function. Human milk is the best and only time proven source of fat and dietary essential fatty acids for infant feeding. International recommendations for n-3 and n-6 EFA dietary intake are reviewed and suggested intakes for long chain EFAs are provided.

Effect of prostanoids and their precursors on the aggregation of rainbow trout thrombocytes.

The role of prostanoids and their precursor fatty acids in the aggregatory response of thrombocytes (platelet equivalents of fish) from the rainbow trout, Oncorhynchus mykiss, was studied. Aggregation of these cells was induced by the thromboxane mimetic U-46619 or arachidonic acid (AA) in the presence of human or trout fibrinogen. The production of TXB2/3 by thrombocytes in response to stimulation with AA was inhibited by aspirin, ibuprofen, and indomethacin. However, thrombocyte aggregation in response to AA stimulation was not significantly altered by these agents at the concentrations tested (10-100 microM), with the exception of indomethacin at 20 and 40 microM. Effects on cytosolic calcium concentration have been suggested as an alternative mechanism for the inhibitory action of indomethacin on human platelet aggregation. The present study, however, failed to identify this as a mechanism for the inhibition of U-46619-induced trout thrombocyte aggregation by indomethacin. The polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid both exhibited an inhibitory effect on U-46619-induced thrombocyte aggregation similar to that observed with mammalian platelets. Unlike the case in mammalian hemostasis, prostacyclin inhibited thrombocyte aggregation only at high concentrations (>5 microM). Prostaglandin E2, however, inhibited thrombocyte aggregation at much lower concentrations (>0.01 microM), suggesting that it may be the major inhibitory eicosanoid in trout.

Carotid surgery for prophylaxis of ischemic stroke

Every year more than 250,000 patients suffer from ischemic (80%) or hemorragic (20%) stroke. Some 40,000 of these strokes are induced by stenosis or occlusion of the extracranial carotid artery. Several randomized studies (NASCET, ECST, ACAS, etc.) have proved that operative removal of high-grade carotid stenoses is an effective method in the primary and secondary prophylaxis of ischemic stroke. Operative therapy is significantly better than medical therapy with thrombocyte aggregation inhibitors. The prerequisite for effective operative prophylaxis is a low perioperative stroke rate. Even though the prophylactic value of carotid thrombarterectomy (TEA) is obvious, only about 5% of all carotid-related strokes are prevented by this operation. Essential conditions for increased efficiency in carotid surgery are close cooperation with the neurologist and the internist, screening of patients with a high risk for ischemic stroke, sophisticated, mainly non-invasive diagnostics, and more operative capacity. Interventional methods (stent, PTA) have not yet been proved safe and effective. These methods should be employed only in special cases after interdisciplinary discussions or in randomized studies.

Frequency and efficacy of glycoprotein IIb/IIIa therapy for treatment of threatened or acute vessel closure in 1332 patients undergoing percutaneous transluminal coronary angioplasty

Background Glycoprotein (GP) IIb/IIIa antagonists are potent inhibitors of thrombocyte aggregation and thrombus formation. Several large-scale randomized studies for prevention of thrombotic complications have shown their potential to reduce these complications in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). It was the purpose of this observational trial to assess the frequency and efficacy of primary GP IIb/IIIa antagonist therapy as a bailout procedure for the prevention of threatened or abrupt vessel closure in patients after conventional balloon angioplasty. Methods And Results From January 1995 to December 1996, PTCA was performed in 1332 consecutive patients with coronary artery disease. Overall, threatened or abrupt vessel closure was observed in 63 (4.7%) patients of the patient population. In these patients, abciximab was administered (0.25 mg/kg body weight intravenous bolus, followed by a 12-hour infusion at 10 μg/min). Repeat PTCA was performed shortly after the administration of the abciximab bolus to achieve an optimal flow at the time of active GP IIb/IIIa therapy. One day after intervention, early follow-up angiography was performed. Follow-up after 1 year included the clinical status of all patients and, if possible, control angiography. Overall, the preintervention minimum lumen diameter (MLD) measured 0.74 ± 0.27 mm and the diameter stenosis was 75% ± 24%. The postintervention MLD increased to 2.60 ± 0.55 mm, and the diameter stenosis decreased to 24% ± 22%. At 24-hour angiographic follow-up, the MLD decreased to 2.47 ± 0.49 mm and the diameter stenosis increased to 28% ± 24%, correspondingly. The thrombus score decreased from 2.8 ± 1.5 before abciximab treatment to 0.88 ± 0.81 after abciximab treatment, and Thrombolysis In Myocardial Infarction flow grade increased from 2.1 ± 1.1 to 2.9 ± 0.3. In-hospital events occurred in 2 patients. Both patients had to undergo emergency coronary artery bypass grafting (1 of these patients died). During long-term follow-up, there were 10 clinical events (1 death, 3 repeat PTCA, and 6 coronary artery bypass graft operations for restenosis at the target lesion site). The cumulative event rate after 1 year (including acute and follow-up events) for both the total group and for the target vessel was 19%. Conclusions The results of this study demonstrate that GP IIb/IIIa antagonists are able to prevent vessel occlusion after PTCA complicated by subsequent threatened or abrupt vessel closure. In these situations, GP IIb/IIIa antagonists provide effective treatment for the reduction of thrombus at the target lesion site, which constitutes a second key element for threatened or abrupt vessel occlusion. (Am Heart J 1999;137:234-40.)

3 Nutritional support of infants and children: Supply and metabolism of lipids

The quantity and quality of dietary lipids and their metabolism are of major importance for the growth, body composition, development and long-term health of children, both in health and disease. Lipids are the major source of energy in early childhood and supply essential lipid-soluble vitamins and polyunsaturated fatty acids that are required in relatively high amounts during early growth. Lipids affect the composition of membrane structures, and modulate membrane functions as well as the functional development of the central nervous system. Some long-chain polyunsaturated fatty acids serve as precursors for bioactive lipid mediators, including prostaglandins, thromboxanes and leukotrienes, which are powerful regulators of numerous cell functions such as thrombocyte aggregation, inflammatory reactions and immune functions. Here we review some aspects of the biochemistry and physiology of lipids and their implications for lipoprotein metabolism, energy balance and the lipid supply during early childhood through the placenta, human milk, enteral diets and parenteral lipid emulsions.

Influence of the low-intensity He-Ne laser radiation on lipid spectrum and thrombocyte aggregation kinetics in peritonitis

Low-intensity He-Ne laser radiation has a modifying effect on lipid exchange in trombocytes, firstly it initiates the start of lipid-dependent signal systems, the intermediates of which are free fatty acids, lisophosphatidylcholin, 1,2-diacylglycerol, phosphatidic acid, phosphatidylinositol, secondly, it stimulates metabolic changes in lipid spectrum, which are attended by the changes of physicochemical states of biomembranes and are of adaptational nature in normal state and compensate-adaptational nature in peritonitis. Laser radiation has a correcting effect on lipid exchange. The lipid component modification of photomodified thrombocytes provokes to a conciderable extent the low level of their aggregational activity in normal state and in peritonitis.

Antithrombotic therapy in chronic coronary syndromes--value of thrombocyte aggregation inhibition, anticoagulation and chronic thrombolysis

Antithrombotic therapy is a basic part in the treatment of acute as well as chronic coronary syndromes. The rationale is an enhanced platelet activity with predomination of procoagulatory mechanisms in coronary artery disease. The current status of antiplatelet drugs, anticoagulation, and chronic thrombolysis used in the treatment of chronic coronary syndromes is discussed. It is concluded that low-dose aspirin is the current drug of choice for long term oral treatment in patients with stable chronic coronary artery disease. In contrast, oral anticoagulation with coumadin should be considered in patients with higher risk for atrial or ventricular thrombosis. The impact of long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris leads to a marked improvement of clinical symptoms. Oral blockade of platelet membrane glycoprotein IIb/IIIa receptor and clinical trials regarding antiischemic effects of low-molecular weight heparins in chronic coronary syndromes are expected for the future.

The effects of in vitro incubation with acetylsalicylic acid on thrombocyte aggregation in whole blood from normal ostriches

Avian thrombocytes are circulating nucleated blood cells which play an active role in both haemostasis and phagocytosis. To better define their role in haemostasis, thrombocyte aggregation was measured in whole blood from healthy adult ostriches using an electrical impedance aggregometer. Thrombocytes were stimulated with collagen (5µg/ml or 1µg/ml), platelet-activating factor (PAF (0.1µ m, 0.01µ m, or 0.001µ m), or ADP (25µ m). Irreversible aggregation occurred consistently in response to collagen or PAF but not to ADP. Aggregation in response to high concentrations of PAF or collagen was not affected by in vitro incubation with 500µ m aspirin. Aggregation in response to low concentrations of PAF or collagen was partially inhibited by in vitro incubation with 500µ m aspirin, suggesting the presence of a prostaglandin-dependent mechanism for regulation of thrombocyte activation similar to that in mammalian platelets.