INTROduCTION Acetylsalicylic acid (ASA) is a first-line drug used in ischemic stroke prophylaxis and therapy. Its partial effectiveness can be caused by the so-called resistance to ASA, which definition indicates to insufficient platelet activity inhibition, measured by aggregometry, platelet function analyzers (PFA-100, Ultegra RPFA, Pla-CorPRT), or flow cytometry. A precise definition based on platelet cyclooxygenase-1 (COX-1) activity maintenance is recommended. Constant thromboxane A 2 synthesis (TxA2) is probably the main mechanism of resistance to ASA. The causes of resistance to ASA involve decreased drug bio activity, drug misuse and its insufficient dose, simultaneous use of other anti-inflammatory drugs, increased platelet activity 1 and their increased formation. Hyperlipidemia, hypercoagulability and TxA2 bio synthesis with cyclooxygenase-2 (COX-2), cyclic superoxides, G 2 and H 2 prostaglandins (PGG 2 /PGH 2) migration from epithelial cells to platelets, and smoking, catecholaminemia, physical exercise, emotional stress, oxidative stress and isoprostane bio synthesis are also of some importance in the occurrence
Mechanical heart compression, including that from mediastinal tumor, may cause Brugada-like ECG pattern. Such ECG pattern might also be observed in intracardiac tumor obstructing the right ventricular out"ow tract (RVOT). Eight cases with Brugada-like ECG and tumors involving RVOT have been described so far; 4 growing in the mediastinum (with one example of in"ammatory mass), 3 with intracardiac location, and 1 being an organized pericardial hematoma. The authors present other 3 cases of intracardiac metastatic tumors in RVOT and Brugada-like ECG pattern with coved ST-segment elevation in the right precordial leads. All patients had negative history of cardiovascular disease or familiar malignant arrhythmia occurrence. ECG were done routinely; none of the patients had chest pain or an increased level of cardiac troponins. In all patients, neoplastic disease was at advanced stage. A 76-year-old male, had a history of four neoplasms: bladder cancer was being treated with chemotherapy, while prostate, tongue, and lung cancers had been resected years ago and no signs of local relapse were found. A 78-year-old female, was diagnosed with colon cancer 1 month after an episode of venous thromboembolism. Six months after the resection of cancer, second focus of adenocarcinoma was found in the rectum. Third patient, a 65-year-old-male had undergone nephrectomy for renal cancer a year before cardiac metastasis diagnosis.
Introduction. Laboratory tests do not reveal any changes due to administration of aspirin (75 – 150 mg/d) in about 25% of patients. The definition of aspirin resistance and parameters of different laboratory tests for its identification have not yet been established. Aim. The aim of our study was to compare the results of platelet aggregation studies, the closure times in PFA-100, the plasma concentrations of 11-dehydro thromboxane B2 (11-d TxB2) and 8-epi prostaglandin F2α (8-epi PgF2α) in patients receiving aspirin chronically. Material. The study group consisted of 22 patients taking aspirin for the secondary prevention of ischemic stroke (IS). All patients were at least 6 months after the acute onset, and had a diminished intraplatelet concentration of malonyldialdehyde due to aspirin ingestion. Methods. Following parameters have been evaluated: Platelet aggregation induced by either ADP (3,5 and 5,0 μM), collagen (2 μg/ml) or arachidonic acid (AA) (0,6 mM); Closure time in PFA-100 (collagen/epinephrine and collagen/ADP cartridges); Plasma 11-d TxB2 and 8-epi PgF2α concentration measured by ELISA method (Cayman Chemicals). Aspirin resistance has been determined by the following criteria: the intensity of ADP induced platelet aggregation ≥ 60%, collagen induced aggregation ≥ 70%, AA induced aggregation ≥ 20%, PFA-100 closure time ≤ 165 s, 11-d TxB2 concentration ≥ mean of the control group ± 2 SD. Results. The frequency of aspirin resistance in patients after ischaemic stroke Aggregation ADP 3,5 μM ADP 5,0 μM Collagen Arachidonic acid PFA-100 11-d TxB2 63,6% 45,5% 18,2% 13,6% 54,5% 50,0% Statistically significant correlations have been found between the plasma concentration of 11-d TxB2 and PFA-100 (Col/Epi) closure times and between plasma concentration of 8-epi PgF2α and PFA-100 (Col/Epi) closure times. There was no difference in mean plasma concentration of 8-epi PgF2α between the group of patients and controls. Conclusions. The most valid laboratory method of aspirin resistance identification in ischemic stroke patients (besides a mesurement of 11-dehydro thromboxane B2) seems to be PFA-100 closure time. Our PFA-100 studies reveal a much higher percentage of aspirin resistance as compared to former studies. The plasma concentration of 8-epi prostaglandin F2α remains in the normal range in patients taking aspirin for the secondary prevention of ischemic stroke.
Background The limited efficacy of secondary prevention for ischaemic stroke may be partially related to aspirin resistance leading to continuous generation of intraplatelet thromboxane A2. Besides other underlying metabolic mechanisms, an oxidant stress along with nonenzymatic biosynthesis of isoprostanes supporting the platelet activation has been suggested. Aims We analyzed the incidence of aspirin resistance in survivors of ischaemic stroke and compared the usefulness of some platelet tests designed for its laboratory exploration. Also we searched for relationship between isoprostane concentration and results of platelet function tests. Material and Methods Forty four patients, at least a month after acute onset of ischaemic stroke were included into the study. All of them have been receiving 75–150 mg aspirin daily at least for a month. The control group for 11-dehydro Thromboxane B2 measurements consisted of 12 healthy volunteers. The platelet function was investigated by platelet aggregation tests induced by either ADP (3.5 and 5.0 μM), collagen (2 μg/ml) or arachidonic acid (AA) (0.6 mM) and by measurement of closure time in PFA-100 analyzer. Thromboxane A2 metabolite - 11-dehydro Thromboxane B2 (11-dTxB2) and isoprostane - 8-epi Prostaglandin F2α (8-epiPgF2α) plasma concentration by immunoenzymatic method (EIA Kits from Cayman Chemicals) were also determined. The aspirin ingestion was controlled by diminished intraplatelet concentration of malonyldialdehyde. Aspirin resistance has been determined by the following criteria: the intensity of platelet aggregation induced by ADP >60%, collagen >70%, AA >20%, PFA-100 closure time <165 s and 11-dTxB2 concentration >mean of the control group minus SD. Results Table 1 Statistically significant inverse correlations have been found between the plasma concentration of 11-dTxB2 and PFA-100 (Col/Epi) closure time (r= −0.31; p= 0.039) as well as between plasma concentration of 8-epiPgF2α and PFA-100 (Col/Epi) closure time (r= −0.36; p= 0.019). Summary/conclusions Laboratory platelet function tests reveal aspirin resistance in almost half of patients after ischaemic stroke. The most significant correlation has been found between plasma concentration of 11-dehydro Thromboxane B2 and PFA-100 closure time. An important interrelationship observed between PFA-100 closure time and plasma concentration of 8-epi Prostaglandin F2α may support the hypothesis of nonenzymatic production of isoprostanoids with platelet proaggregatory activity, playing a role in aspirin resistance. The frequency of aspirin resistance in patients after ischaemic stroke ADP 3.5μM ADP 5.0μM Collagen Arachidonic acid PFA-100 11-dTxB2 45% 52% 20% 7% 52% 43%
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