Antiplatelet Therapy Resistance Research Articles

P210 PLATELET REACTIVITY IN ELDERLY PATIENTS WITH ACUTE CORONARY SYNDROME AND ATRIAL FIBRILLATION

Abstract Background Previous studies showed that incidence of antiplatelet therapy resistance is higher in elderly patients. There is a paucity of data about the response to antiplatelet therapy in patients with atrial fibrillation (AF). The purpose of this study is to analyze platelet reactivity during dual antiplatelet therapy (DAPT) in elderly patients (≥ 75 years) with acute coronary syndrome (ACS), stratifying them by the presence or absence of AF. Methods From the PRATO–ACS registry we selected 160 patients (81±5 years; 45% female) treated with DAPT (Aspirin 100 mg daily and Clopidogrel 75 mg daily). At discharge they were tested with the VerifyNow assay to measure platelet reactivity in aspirin (aspirin–reaction unit – ARU) and in clopidogrel (P2Y12–reaction unit – PRU). Low response to aspirin was defined as ARU ≥550; low response to clopidogrel was defined as PRU ≥ 208; high response was defined as PRU values ≤ 85. Results The ARU and PRU values for patients divided according to the presence of AF are shown in the Figure 1. Conclusions In this series of elderly ACS patients, AF was associated with higher residual platelet reactivity under both clopidogrel and aspirin. AF patients were significantly more clopidogrel low responders than non–AF, while non–AF patients were significantly more high responders. No difference was found for aspirin low responders between AF and no AF patients.

Pharmacoeconomic analysis of personalized antiplatelet therapy in patients with acute coronary syndromer

Relevance. The problem of antiplatelet therapy resistance is not fully solved, whereas its manifestations in the form of stent thrombosis cause a negative contribution in treatment and can lead to significant economic damage to the healthcare system. Pharmacogenetic testing as a personalization tool can potentially reduce the cost of treatment, which requires pharmacoeconomic research of pharmacogenetic methods. The aim of this study was a pharmacoeconomic evaluation of the pharmacogenetic testing implementation before the antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention. Methods. In our study, a decision tree model was built with a time horizon of 1 year and a cost-effectiveness analysis was performed for six compared treatment strategies in patients with acute coronary syndrome after stent implantation with and without genotyping for the drugs clopidogrel, ticagrelor and prasugrel. Results. A treatment strategy with pharmacogenetic testing and the choosing of prasugrel for slow and intermediate metabolizers was the most preferred with CER 35 577.40 rubles per 1 unit of effectiveness. The most expensive strategy was the “blind” use of ticagrelor for all patients. Conclusion. Based on the modeling results, it can be concluded that the implementation of pharmacogenetic testing before prescribing antiplatelet drugs in patients with acute coronary syndrome undergoing stenting can potentially reduce the incidence of adverse events such as stent thrombosis and reduce the overall cost of treatment.

747 HIGH PLATELET REACTIVITY AFTER DAPT IN PATIENTS WITH ACUTE CORONARY SYNDROME AND ATRIAL FIBRILLATION

Abstract Background The incidence of atrial fibrillation (AF) in patients who undergo percutaneous coronary intervention (PCI) is not negligible, especially in the elderly. Both oral anticoagulation (OAC) and dual anti-platelet therapy (DAPT) are recommended by main guidelines, therefore is essential to balance the prevention of ischemic events with the risk of bleeding. Evidences from literature suggest that incidence of anti-platelet therapy resistance is higher in elderly patients. There is a paucity of data about the response to antiplatelet therapy in patients with AF. The purpose of this study is to analyze platelet reactivity during DAPT (aspirin + clopidogrel) in elderly patients hospitalized for acute coronary syndrome (ACS), stratifying them by the presence or absence of AF. Methods We analyzed data of patients admitted to our center for ACS. All patients were ≥ 75 years old and treated with DAPT (Aspirin 100 mg daily and Clopidogrel 75 mg daily). At discharge they were tested with a point-of-care antiplatelet-function test (VerifyNow assay) to assess the platelet response to aspirin in aspirin-reaction units (ARU) and to clopidogrel in P2Y12-reaction units (PRU). Low response to aspirin was defined as ARU ≥550; low response to clopidogrel was defined as PRU ≥208; high response was defined as PRU values ≤ 85. Results Among the 216 patients included in the registry we selected 154 of these [median age 81 (IQR 77-87) years; 45% female] who were submitted to the platelet function tested before discharge. Patients were divided into two groups: AF (43 pts); non-AF (111 pts). The table shows the platelet reactivity values by two groups. Conclusions In this series of elderly patients with ACS, AF was associated with higher residual platelet reactivity with both clopidogrel and aspirin. AF patients were significantly less responsive to clopidogrel than non-AF, while among non-AF patients there were significantly more high responders. No difference was found for aspirin low responders between AF and non-AF group. This evidence could assume clinical significance in the choice of antiplatelet drugs to be combined with chronic anticoagulant therapy for AF.

Three cases of dual antiplatelet therapy resistance in patients undergoing carotid artery stenting and stent assisted coil embolization

Background: Dual antiplatelet therapy (DAPT) was generally performed in carotid artery stenting (CAS) and stent assisted coil embolization for the prevention of ischemic complication. However, there is no standard rule in patients with DAPT resistance.

Abstract 6: Interim Report of the Weave Trial: First 102 Consecutive on Label Patients

Purpose: The initial FDA approval trial of the self-expanding Wingspan stent for symptomatic intracranial atherosclerotic disease demonstrated a 4.5% periprocedural complication rate. Subsequently, similar on-label registry data was reported. The WEAVE Trial is a prospective, consecutive enrollment, single-arm, post-market surveillance trial evaluating periprocedural outcomes in patients with the revised FDA indications for use. Methods: Data for the first 102 on-label patients for which completed data is available are included in this report. The primary analysis endpoints included periprocedural stroke, death, or symptomatic bleed within 72 hours of the stenting procedure in patients who were treated on label. A subgroup of the participating sites included anti-platelet therapy resistance testing and correction, if needed, in their treatment of the patient. All patient outcomes were separately adjudicated by a stroke Neurologist by 72 to 96 hours post procedure. Results: In the initial 122 consecutive patients enrolled with completed data, 102 patients were treated on label and are included in the primary analysis, and 20 patients were treated off label and were part of secondary analyses. The mean stenosis in the primary analysis group was 83% with target artery break down as follows: 40.2% MCA, 25.5% ICA, 19.6% Basilar, 14.7% Vertebral or VB junction. Of the 102 patients in the primary analysis, 3 patients (2.9%) reached a primary endpoint of stroke, symptomatic bleed, or death within 72 hours. In the off label group, 4 of the 20 patients (20%) reached a primary endpoint within that period. Conclusions: The early interim analysis of the first 102 patients of WEAVE trial has demonstrated a very low periprocedural morbidity and mortality of 2.9%. This is lower than the high periprocedural event rate in the SAMMPRIS trial, and statistically better than the outcomes in the off label group (Fisher’s Exact test p value 0.014). This early data provides impetus to continue to collect data in this trial, and lends support to the concept that refined patient selection criteria and establishment of best practice techniques and management for these patients can substantially decrease the peri-procedural risk of intracranial stenting.

Anti-platelet Therapy Resistance - Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities.

It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or non-responders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.

Antiplatelet Therapy in Carotid Artery Stenting and Carotid Endarterectomy in the Asymptomatic Carotid Surgery Trial-2

Strokes are infrequent but potentially serious complications following carotid intervention, but antiplatelet therapy can reduce these risks. There are currently no specific guidelines on dose or duration of peri-procedural antiplatelet treatment for patients undergoing carotid intervention. Within the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), this study aimed at assessing the current use of antiplatelet therapy before, during, and after CEA and CAS in patients with asymptomatic carotid stenosis. Questionnaires were sent to ACST-2 collaborators seeking information about the use of antiplatelet therapy during the pre-, peri-, and post-operative periods in patients undergoing carotid intervention at 77 participating sites and also whether sites tested for antiplatelet therapy resistance. The response rate was 68/77 (88%). For CAS, 82% of sites used dual antiplatelet therapy (DAPT) pre-operatively and 86% post-operatively with a mean post-procedural duration of 3 months (range 1-12), while 9% continued DAPT life-long. For CEA only 31% used DAPT pre-operatively, 24% post-operatively with a mean post-procedural duration of 3 months (range 1-5), while 10% continued DAPT life-long. For those prescribing post-procedural mono antiplatelet (MAPT) therapy (76%), aspirin was more commonly prescribed (59%) than clopidogrel (6%) and 11% of centres did not show a preference for either aspirin or clopidogrel. Eleven centres (16%) tested for antiplatelet therapy resistance. There appears to be broad agreement on the use of antiplatelet therapy in ACST-2 patients undergoing carotid artery stenting and surgery. Although evidence to help guide the duration of peri-procedural antiplatelet therapy is limited, long-term treatment with DAPT appears similar between both treatment arms.

Doble terapia antiagregante en el postoperatorio de cirugía coronaria: revisión bibliográfica

IntroductionExtensive and early use of acetyl-salicylic acid (ASA) is widely accepted in the post-operative period after coronary artery bypass grafting surgery (CABG), however, its combination in double antiplatelet therapy (DAT) is still controversial. DAT may improve coronary graft patency due to a lower vulnerability against constitutive and/or transient antiplatelet therapy resistance, and due to potential pleiotropic effects against intimal hyperplasia. Nevertheless, dosage and duration of the treatment are not completely established. MethodsSystematic bibliographic review in Medline combining 3 clusters of key words and stepwise selection of articles obtained. ResultsOut of a total of 56 preliminary studies found, 19 were chosen for analysis, of which 7 were randomised controlled trials, 2 meta-analyses, 1 literature review, 3 clinical guidelines, and 6 non-randomised studies. All of them were individually analysed and classified as favourable or not to DAT. ConclusionsThere is not enough evidence to warrant extensive use of DAT after CABG. However, DAT could show a benefit in certain clinical scenarios, such as CABG after prior coronary acute syndrome, extensive use of venous grafts, or CABG off-pump. The benefits shown in studies favourable to DAT on the improvement of coronary graft patency in the short-midterm did not lead to differences in the incidence of major cardiovascular events. Neither of the groups showed differences in terms of safety related to haemorrhagic events, nor in the immediate postoperative or follow-up period

E-062 Intracranial Stenting for Atherosclerotic Disease with Aggressive Anti-platelet Therapy Management: A Consecutive Series of 154 Patients

IntroductionContemporary studies of intracranial stenting have utilised standard or aggressive medical therapy involving dual anti-platelet therapy, but have not evaluated anti-platelet therapy resistance as a component of treatment failure.MethodsThe current...

Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses.

The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies.In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s−1) and therapy concentrations (0–2.4 µM for eptifibatide, 0–2 mM for acetyl-salicylic acid (ASA), 3.5–40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models.Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment.

Impact and Diagnosis of Antiplatelet Therapy Resistance in Patients Undergoing Cardiac Surgery

Abstract Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Coronary artery bypass grafting (CABG) is highly effective in the treatment of severe coronary artery disease. Antiplatelet therapy is a critical component of the medical management of patients following CABG. Patient idiosyncrasies in responsiveness to antiplatelet agents, however, lead to variable suppression of platelet aggregation. This problem is underscored by inconsistent findings from the different laboratory instruments used to document antiplatelet drug responsiveness and its uncertain clinical impact. The laboratory results reveal a spectrum of platelet inhibition effects. The cutoff values discriminating between “resistance” and “response” to antiplatelet therapy often rely solely on definition. It is therefore not surprising that regular testing for antiplatelet therapy response has neither been routinely instituted in a wider clinical arena nor is there unequivocal evidence to support it. The purpose of this review is to offer insight into the incidence and clinical impact of antiplatelet therapy resistance in patients undergoing surgical myocardial revascularization.

The clinical effect of resistance to antiplatelet therapy and high-dose statin therapy in acute coronary syndrome

Purpose: The aim of this study was to determine whether there is an association between antiplatelet therapy resistance and systemic inflammation in patients with acute coronary syndrome (ACS). Methods: We included 122 patients with ACS hospitalized at Moscow City Hospital 23. We measured platelet function using simultaneous light transmittance aggregometry (spontaneous aggregation and ADP-induced), Thromboelastography Platelet Mapping (TEG-PM), and VerifyNow Aspirin and P2Y12 assays. The following markers of systemic inflammation were estimated: white blood cell count and plasma levels of high sensitivity C-reactive protein (hsCRP), soluble CD40-ligand (sCD40L), sP-selectin, fibrinogen. All patients received aspirin at 250–325 mg and a loading dose of clopidogrel (300–600 mg) on arrival, followed by 125 mg of aspirin and 75 mg of clopidogrel per day. For the following analysis, the patients were separated into two groups. Both groups received atorvastatin: one group at 20 mg per day (N = 18) and the second at 80 mg per day (N = 24) for at least 7 days. Results: We found that patients with elevated levels of plasma von Willebrand factor had increased 5 μM ADP–induced platelet aggregation (p=0.044). High white blood cell counts were associated with increased levels of 10 μM ADP-induced platelet aggregation (p=0.0043). High plasma levels of sP-selectin were associated with high levels of ADPtest (Multiplate) and high percentages of P2Y12-inhibition (VerifyNow) (p=0.046 and 0.047, respectively). Kaplan-Meier survival analysis with a logrank significance test showed an association between a high risk of reinfarction during follow-up (1–22 months after ACS) and high levels both of 10 μM ADP–induced platelet aggregation and of HPR ADP (p = 0.014 and 0.006, respectively). We found that this association remains significant among patients with high levels of hs-CRP (p = 0.021), while in the group of patients with low levels of hs-CRP this relationship was not significant. Among patients receiving atorvastatin at 20 mg, the association between a high risk of reinfarction and high levels of platelet aggregation also remained significant (p = 0.003). In contrast, among patients receiving atorvastatin at 80 mg, this association disappeared. Conclusions: In our study, we found that high on-treatment platelet reactivity is associated with several laboratory signs of systemic inflammation and predicts a poor prognosis in patients with ACS. High-dose statin therapy can overcome the association between high on-treatment platelet reactivity and poor prognosis in patients with ACS.

Advances in Our Understanding of “Resistance” to Antiplatelet Agents for Prevention of Ischemic Stroke

We review the role of aspirin and clopidogrel for prevention of ischemic stroke and explore the concept of antiplatelet therapy resistance both from a laboratory and clinical perspective and genetic polymorphisms that might influence platelet reactivity with clopidogrel administration. Debates have raged over the years about the application of platelet function tests in clinical practice. We conclude that platelet function testing is not indicated in routine clinical practice. This recommendation is supported by clinical guideline statements, a lack of a global platelet function measure, and limitations of current platelet function test methods as applied in practice. We discuss a recently hypothesized hierarchy of patient characteristics in relation to which patients are most likely to benefit from platelet function studies based on acuity (i.e., risk) of cardiovascular disease. A focus of antiplatelet therapy administration should include emphasis on compliance/adherence and in the example of aspirin, use of well-absorbed forms of aspirin and avoidance of drugs that may interact with aspirin to inhibit its mechanism of action (e.g., certain nonsteroidal anti-inflammatory drugs).

A case–control study on platelet reactivity in patients with coronary stent thrombosis

The pathophysiology of stent thrombosis (ST) has evolved from the identification of single causative factors to a complex multifactorial model. The aim of the present study was to investigate whether patients with a history of ST exhibit heightened platelet reactivity to clopidogrel and aspirin. Pretreatment and on-treatment platelet reactivity to clopidogrel and aspirin, as well as dual antiplatelet therapy resistance, was determined in 84 patients with a history of definite ST (cases: 41 early ST; 43 late ST) and in 103 control patients with a previously implanted coronary stent but no ST after the index procedure. Platelet function was evaluated with optical aggregometry, the VerifyNow P2Y12 and aspirin assays, the PFA-100 Innovance P2Y* cartridge, the flow cytometric vasodilator-stimulated phosphoprotein assay and urine 11-dehydrothromboxane B(2) measurement before and after the administration of a 600-mg loading dose of clopidogrel and 100 mg of aspirin. The study was registered at ClinicalTrials.gov, number NCT01012544. Patients with a history of early ST clearly demonstrated higher on-clopidogrel platelet reactivity than controls. Patients with both early and late ST exhibited heightened on-aspirin platelet reactivity status, and dual antiplatelet therapy resistance was more frequent. Patients with a history of early ST exhibit a poor response to clopidogrel. Furthermore, both early and late ST are strongly and independently associated with heightened on-aspirin platelet reactivity, and dual antiplatelet therapy resistance is more frequent.

ON THE 125TH ANNIVERSARY OF ACETYLSALICYLIC ACID

An experience of acetylsalicylic acid (ASA) clinical use since its synthesis in 1887 is highlighted. ASA modes of action and its position among the modern antiplatelet agents are considered. The evidence based clinical data on ASA treatment and the problem of antiplatelet therapy resistance are discussed. ASA interaction with other drugs and ASA pleiotropic effects are reviewed

Anti-Platelet Therapy and Aspirin Resistance – Clinically and Chemically Relevant?

Platelets play a central role in the pathogenesis of the atherothrombosis which ultimately causes myocardial infarction, stroke and peripheral vascular disease. Commonly used oral anti-platelet drugs include aspirin (an irreversible inhibitor of cyclo-oxygenase), clopidogrel (an ADP receptor antagonist), other thienopyridines such as ticlopidine and prasgruel, and dipyridamole (an inhibitor of adenosine reuptake and platelet phosphodiesterase). Newer agents are in development and one, ticagrelor, a reversible ADP receptor antagonist has shown promise. Despite their proven benefit, recurrent vascular events still occur in those taking anti-platelet drugs. This has led to the concept of anti-platelet resistance, most commonly aspirin resistance as this drug is the cornerstone of most regimens. The causes of aspirin resistance are numerous but potential mechanisms include lack of patient adherence, non COX-1 mediated thromboxane A2 synthesis, increased activity of alternate platelet activation pathways, interference of aspirin action by other drugs and probably pharmacogenetic factors. Measurement of platelet response to aspirin is made possible using a number of in-vitro laboratory assays of platelet function which include measurement of thromboxane A2 metabolites as well as newer point-of-care assays of platelet aggregation. The phenomenon of aspirin resistance is important as it raises the possibility of developing strategies to identify those who respond best to a particular anti-platelet regimen, or to development of newer anti-platelet therapies to which more patients respond. This review discusses important aspects of aspirin resistance both in terms of clinical medicine, alternative anti-platelet strategies, and the potential to overcome its various causes.

(−)-Epigallocatechin-3-gallate decreases thrombin/paclitaxel-induced endothelial tissue factor expression via the inhibition of c-Jun terminal NH2 kinase phosphorylation

Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (−)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6h up to a concentration of 25μmol/L. At a concentration of 25μmol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease in TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-κB nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.

Comprehensive Quality Management of Multiple Electrode Platelet Aggregometry.

Abstract 4463Platelet function analysis provides quantitative results which may reveal platelet disorders, platelet inhibition during anti-platelet therapy or anti-platelet drug resistance. The results may have important consequences on patients therapy. As in all laboratory methods, a comprehensive quality management approach is crucial and increasingly demanded by regulatory authorities.In platelet function methods quality control is hampered by the fact that platelets are not stable over longer time periods and loose their functional activities after freezing and freeze-drying. Therefore for most platelet function tests no control materials are available. When no biological quality control material is available, it is even more important to install and maintain a quality management approach, which covers as many influence factors and sources of error as possible. Here we present the quality management procedures of Multiple Electrode Aggregometry (MEA) a relative new platelet function test based on the analysis of whole blood (Multiplate analyzer, Dynabyte medical, Munich, Germany).In the MEA device temperature of the measurement system is controlled by the analyser and can be verified by an external QC kit. The signal reaction of this method is based on the rise of electrical resistance induced by the adhesion and aggregation of activated blood platelets on metal sensor electrodes in a disposable test cell. In order to control possible sensor inconsistencies and improve precision, the test cell incorporates two independent sensor units, each consisting of 2 silver-coated highly conductive wires. The duplicate sensors thus serve as an internal control. During each measurement Pearson's correlation coefficient of single measurements of the curves assessed by the two electrode pairs and the difference of the two AUCs are calculated automatically by the analyzer's software. The result is flagged if the values are outside of the acceptance range (correlation coefficient <0.98, difference to the mean curve >20%). The instrument has an integrated procedure for an electronic control which checks the function of the electronic amplifier in the analyzer. In addition liquid controls are available, based on solutions with different ional strength. Using these solutions the instrument, pipettor and test cells are controlled. Using blood from a healthy individual, users can control qualitatively all aspects of the analysis (instrument, test cells, reagents, pipettor). Abnormal control reagents are available, containing either aspirin, a GpIIbIIIa antagonist or prostaglandin E1, which can produce an abnormal result when added to a normal blood sample before the analysis. The instrument provides an electronic pipettor with interactive software-guided operation procedures, which help standardise the analysis and minimize user-related errors. Using artificial liquid control materials a pilot external QC was performed in 6 individual centers and the results were centrally analyzed. Level I control was determined as 125+-6 aggregation units (AU, mean+-sd), level II control was 64+-5 AU. Coefficients of variation of all determinations were 4.6% and 7.3% respectively.In conclusion it is shown that while a stable biological control material for platelet function analysis is not available, it is possible to perform quality controls covering many parts of the analytical procedure. Manufacturers and users of platelet function tests should try to implement control procedures that cover as many aspects of the technology they apply as possible to ensure correct performance of the tests over the lifetime of the instrument, test cells and reagents. As long as stable biological quality control materials for platelet function analysis are not available, qualitative biological controls using normal blood or plasma should be combined with artificial control materials or electronic test procedures according to the analytical reaction which is performed. If the biological reaction cannot be quantitatively controlled, then at least the physical process leading to the signal of the respective test procedure should be verified (measurement of pressure, optical density or electrical impedance). Using a step by step approach comprehensive quality management of platelet function analysis is feasible and should be implemented in routine. Disclosures:Calatzis:Dynabyte Medical : Equity Ownership, Patents & Royalties.

ANTIPLATELET THERAPY RESISTANCE IN PATIENTS WITH ACUTE CORONARY SYNDROME WITH ST-SEGMENT ELEVATION

Aim. To evaluate the incidence of acetylsalicylic acid (ASA) and clopidogrel resistance in patients with acute coronary syndrome with ST-segment elevation and to find out possible clinical factors, contributing to this state. Material and methods. 58 patients with acute coronary syndrome with ST-segment elevation (49 men, 9 women) were included into the study. Age of patients ranged from 37 tо 84 y.o. (60,8±12,3 y.o. in average). Platelet aggregation was assessed by the Born’s method. Level of arachidonic acidinduced aggregation ≥20% considered as ASA resistance. Decreasing of ADP-induced platelet aggregation ≥20% considered as ASA resistance. Decreasing of ADP-induced platelet aggregation <10%, 10-29%, and ≥30% compared to the basal level considered as clopidogrel resistance, “partial clopidogrel resistance” or clopidogrel sensitiveness, respectively. Results . ASA and clopidogrel decreased arachidonic acid-induced and ADP-induced aggregation after 7 days of the therapy compared to the basal levels (р<0,05). The highest incidence of resistance was registered in patients with diabetes mellitus (71,1% to ASA, 57,1% to clopidogrel) and obe-sity (42,9% to clopidogrel). Conclusion. The incidence of ASA and clopidogrel resistance reached to 28,9% and 24,4% respectively in patients with acute coronary syndrome with ST-segment elevation. The prevalence of antiplatelet therapy resistance is significantly higher in patients with diabetes mellitus and obesity (р<0,05). The incidence of early complications of acute myocardial infarction is higher in patients resistant to ASA and clopidogrel.