Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples

Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established. We assessed platelet function in whole blood samples of healthy volunteers at decreasing platelet counts (> 100, 80-100, 50-80, 30-50 and < 30 x109/L) using two POC tests: impedance aggregometry and in-vitro bleeding time. Flow cytometry served as the gold standard. The number of platelets needed to reach 50% of the maximum function (ED50) and the lower reference limit (EDref) were calculated to define limits of test validity. The minimal platelet count required for reliable test results was 100 x109/L for impedance aggregometry and in-vitro bleeding time but only 30 x109/L for flow cytometry. Comparison of ED50 and EDref showed significantly lower values for flow cytometry than either POC test (P value < 0.05) but no difference between POC tests nor between the used platelet agonists within a test method. Calculating the ED50 and EDref provides an effective way to compare values from different platelet function assays. Flow cytometry enables correct platelet function testing as long as platelet count is > 30 x109/L whereas impedance aggregometry and in-vitro bleeding time are inconsistent unless platelet count is > 100 x109/L

Daltonplan goes University : Die Anwendung des reformpädagogischen Konzeptes, Daltonplan in der Bachelorausbildung für Gesundheits- und Krankenpflege, mit Beispielen für das Fertigkeitentraining

Diese Arbeit untersucht die Eignung des reformpädagogischen Konzeptes des Daltonplans für dessen Anwendung an einer Hochschule, speziell in der Bachelorausbildung Gesundheits- und Krankenpflege an der FH Campus Wien. Der erste Teil dieser Arbeit basiert auf der hermeneutischen Forschungsmethode und konzentriert sich auf die Darstellung des Daltonplans und seine Eignung als methodisches Konzept für eine Hochschule. Die Frage nach der Anwendbarkeit wird unter Einbeziehung der Didaktik in der Erwachsenenbildung und einer diversitätssensiblen Didaktik beantwortet. Um die theoretischen Erkenntnisse über eine mögliche Anwendung des Daltonplans empirisch zu ergänzen, wurden Expertinnen-/Experteninterviews durchgeführt und die Inhaltsanalyse der Interviews in die Bearbeitung der Forschungsfragen miteinbezogen. Auf der Basis der Forschungsergebnisse werden in der Arbeit Möglichkeiten und Bedingungen zur Anwendung des Daltonplans an einer Hochschule aufgezeigt. Der Schwerpunkt liegt dabei auf der Anwendung des Daltonplans im tertiären Bildungssektor und in der Nursingeducation. Die dargestellten Beispiele für die Anwendung des Daltonplans sind an die Bachelorausbildung in der Gesundheits- und Krankenpflege angepasst. Diese Masterarbeit bietet einen Erkenntnisgewinn und einen methodischen Mehrwert für Lehrende im tertiären Bildungssektor, die an der Anwendung von reformpädagogischen Konzepten interessiert sind.This paper examines the progressive educational concept of the Dalton Plan for its suitability of applying it at universities, specifically in the Bachelors degree for healthcare and nursing at the FH Campus Wien. The first part of this paper is based on the hermeneutical research method and focuses on describing the Dalton Plan and its suitability as methodological concept at a university. The question of applicability will be answered, taking into account the didactics of adult education as well as diversity-conscious didactics. In order to empirically complete the theoretical insights into a possible application of the Dalton Plan, interviews with experts have been conducted and the content analysis of the interviews has been included in the development of the research questions. Based on the research outcomes, possibilities and conditions for the Dalton Plans application at universities are presented in the paper. The main emphasis lies on the application of the Dalton Plan within tertiary education and nursing education. The described examples for the application of the Dalton Plan are adapted to the Bachelors degree in health care and nursing. This master thesis offers insights and methodological added value for teachers in the tertiary education sector, who are interested in the application of progressive educational concepts.Wien, FH Campus Wien, Masterarb., 2017(VLID)239322

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Underlying mechanism and specific prevention of hemolysis-induced platelet activation

<p>Thromboembolic complications significantly impair the outcome of hemolytic disorders. We hypothesized that red cell adenosine diphosphate (ADP) release results in significant platelet activation in hemolysis and that this prothrombotic state can be prevented by inhibition of the ADP P2Y₁₂ receptor. In the current study, we therefore sought to investigate the mechanism and inhibition of hemolysis-induced platelet activation. The expression of activated integrin αIIbß3 was determined by flow cytometry, and platelet aggregation was assessed by multiple electrode platelet aggregometry. We demonstrate platelet activation and increased platelet aggregation by adding hemolytic blood (lysates) to whole blood, similarly to that achieved by the platelet agonist ADP. Enhanced platelet activation and reactivity in the presence of hemolytic blood were significantly abolished by apyrase, which catalyzes ADP degradation, and inhibited by blockade of the platelet ADP P2Y₁₂ receptor with cangrelor. Platelets from patients treated with the ADP P2Y₁₂ receptor antagonist clopidogrel showed a reduced response to lysates compared to platelets from healthy controls without antiplatelet treatment. Further, <i>in vitro</i> blood group ABO incompatibility induced hemolysis and led to increased platelet activation. Finally, “spontaneous” platelet aggregation seen in patients with cold agglutinin disease was completely abolished by cangrelor. In conclusion, hemolysis is associated with increased platelet activation and aggregation due to red cell derived ADP, which can be prevented by ADP receptor blockade.</p

Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome

Bleeding events in patients with acute coronary syndrome (ACS) are a risk factor for adverse outcomes, including mortality. We investigated the association of growth differentiation factor (GDF)-15, an established predictor of bleeding complications, with on-treatment platelet reactivity in ACS patients undergoing coronary stenting receiving prasugrel or ticagrelor. Platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to adenosine diphosphate (ADP), arachidonic acid (AA), thrombin receptor-activating peptide (TRAP, a protease-activated receptor-1 (PAR-1) agonist), AYPGKF (a PAR-4 agonist) and collagen (COL). GDF-15 levels were measured using a commercially available assay. GDF-15 correlated inversely with MEA ADP (r = −0.202, p = 0.004), MEA AA (r = −0.139, p = 0.048) and MEA TRAP (r = −0.190, p = 0.007). After adjustment, GDF-15 was significantly associated with MEA TRAP (β = −0.150, p = 0.044), whereas no significant associations were detectable for the other agonists. Patients with low platelet reactivity in response to ADP had significantly higher GDF-15 levels (p = 0.005). In conclusion, GDF-15 is inversely associated with TRAP-inducible platelet aggregation in ACS patients treated with state-of-the-art antiplatelet therapy and significantly elevated in patients with low platelet reactivity in response to ADP