Comparison of Heparin Vs. Lepirudin Anticoagulated Tubes for The
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Usage of heparin anticoagulated tubes for the MEA 275 Applied Cardiopulmonary Pathophysiology 17: 275-283, 2013 Comparison of heparin vs. lepirudin anticoagulated tubes for the assessment of ASS-induced platelet dysfunction using the Multiplate device Haitham Mutlak 1, Christian Rehse 1, Bertram Scheller 1, Peter Stein 1, Andreas Pape 1, Nestoras Papadopoulos 2, Elisabeth Hannah Adam 1, Christian Friedrich Weber 1 1 Department of Anesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Germany 2 Department of Thoracic and Cardiovascular Surgery, University Hospital Frankfurt, Germany Abstract Background: The manufacturer of the Multiplate® device recommends usage of lepirudin anticoag - ulated blood samples. It was the aim of the present study to analyze a potential relationship be - tween blood samples that were drawn into lepirudin versus heparin anticoagulated tubes. Methods: In a prospective cohort, single-center study, patients scheduled for elective coronary ar - tery bypass grafting were preoperatively screened for eligibility. Patients were enrolled into the study if they had ceased any antiplatelet therapy for at least five days prior to the planned surgical intervention. Lepirudin and heparin anticoagulated blood samples were taken at the evening be - fore surgery (T1), 4 h after the first postoperative ingestion of 100 mg aspirin (T2) and five days af - ter begin of daily aspirin therapy (T3). Results: n = 75 patients were finally enrolled into the study. There was a significant correlation be - tween lepirudin and heparin anticoagulated samples at each measuring point. Platelet aggregabili - ty was higher in lepirudin anticoagulated blood as compared to heparin anticoagulated blood. Conclusions: Data of the present study show that heparin anticoagulated blood samples are suit - able for the assessment of arachidonic acid induced platelet aggregation of unaffected platelets as well as platelets with aspirin associated reduced aggregability. Key Words: Heparin, Multiplate, Multiple Electrode Aggregometry, Platelet function testing, Point- of-Care in perioperative care [2]. Generally, vis - Introduction coelastic measures, which are used to ana - Conventional laboratory coagulation analy - lyze the plasmatic coagulation system, are ses (INR, aPTT, platelet count, fibrinogen differentiated from aggregometric measures. concentration) are of limited use for the pre - Aggregometric measures are used to screen diction and detection of perioperative coag - for disorders of primary hemostasis, such ulopathies and for the monitoring of their as (acquired) platelet dysfunctions and treatment [1]. Because the so-called “Point- allow the quantification of the effect of an - of-Care” (POC) tests may partly compensate tiplatelet medications. In this context, aggre - for the methodological limitations and diag - gometric measures indicate low- or non- nostic shortfalls of conventional coagulation responsiveness to aspirin and/or clopidogrel testing, these methods are increasingly used [3]. 276 H. Mutlak, C. Rehse, B. Scheller, P. Stein, A. Pape, N. Papadopoulos, E. H. Adam, C. F. Weber The Multiplate® analyzer, which is based therapy five days prior to the date of planned on Multiple Electrode Aggregometry (MEA, surgical intervention. All patients gave writ - Roche AG, Grenzach, Germany) [4], is one ten informed consent. Pregnancy was de - of the standard devices for periprocedural fined as exclusion criterion. monitoring of platelet function, both in inter - nal medicine [5] and in perioperative care [6]. Considering the transient platelet activat - Anesthetic management ing effects of heparin [7, 8], the manufactur - On the evening prior to surgery, patients er recommends usage of lepirudin anticoag - were given 20 mg clorazepat dipotassium ulated tubes for blood drawing. However, in (Tranxilium®, Sanofi-Aventis GmbH, comparison to lepirudin, usage of heparin Hoechst, Germany). After routine monitor - anticoagulated tubes is more applicable be - ing was applied, general anesthesia was in - cause of their exceptional availability all duced with 0.3–1 µg/kg sufentanil (Sufenta®, over the hospital. Furthermore usage of he - Janssen-Cilag GmbH, Neuss, Germany), parin anticoagulated tubes is relative low- 1–2.5 mg/kg propofol (Disoprivan®, As - priced and favorable even economic rea - traZeneca GmbH, Wedel, Germany), and sons. Although recommended in commonly 0.6 mg/kg rocuronium (Esmeron®, Essex accepted hemotherapy algorithms [9, 10], GmbH, Munich, Germany). For the mainte - accuracy of measures from heparin anticoag - nance of general anesthesia, all patients re - ulated samples had not been studied yet. ceived 1–2 Vol% sevoflurane (Sevoran®, Ab - Therefore, it was the aim of the present study bott, Wiesbaden, Germany) and intermittent to evaluate the relationship of MEA analyses boluses of sufentanil. Both isotonic crystal - performed in lepirudin versus heparin anti - loid (Sterofundin®, B.Braun GmbH, Melsun - coagulated blood samples. gen, Germany) and colloid fluids (6% HES 130/0.4, Voluven®, Fresenius Cabi, Bad Homburg, Germany) were perioperatively Methods infused based on institutional standards. Trial design Management of extracorporeal This prospective cohort, single-center study circulation was conducted at the University Hospital The extracorporeal circuit included a mem - Frankfurt am Main, Germany. The present brane oxygenator (Quadrox® oxygenator, study complies with the declaration of Maquet Cardiopulmonary AG, Hirrlingen, Helsinki and was approved by the local Sci - Germany) and a roller pump system (HL20, entific and Ethics Review Board (filed with Maquet Cardiopulmonary AG) equipped the reference number 91-08). with a heat exchanger (Plegiox®, Maquet Cardiopulmonary AG). The circuit was primed with 500 ml crystalloid solution Participants (Sterofundin®, B.Braun Melsungen AG), 500 Patients were suitable for this trial after two ml colloid solution (6% HES 130/0·4, Volu - inclusion steps. ven®, Fresenius Medical Care AG), and 250 Step 1: Patients (age 18 years or older) ml 20% Mannitol (Mannitol Baxter®, Baxter, scheduled for elective coronary artery by - Unterschleissheim, Germany). Heparin (He - pass grafting (CABG) with cardiopulmonary parin-Natrium Braun®, B.Braun Melsungen bypass (CPB) were preoperatively screened AG) was repeatedly administered after an ini - for eligibility. tial bolus of 400 IU/kg to maintain an activat - Step 2: Patients were enrolled into the ed clotting time (ACT) of > 400 s. During study, if they had ceased any antiplatelet CPB, a non-pulsatile flow was maintained at Usage of heparin anticoagulated tubes for the MEA 277 2.6-3 l/min/m², and the mean arterial blood AG&Co) and a 4.7 ml EDTA tube (Sarstedt pressure was targeted to 50–70 mmHg with AG). the addition of norepinephrine (Arterenol®, Sanofi-Aventis GmbH, Hoechst, Germany) if needed. Myocardial protection was achieved Multiple Electrode Aggregometry with cold blood cardioplegia (20°C). Antifib - (MEA) rinolytic therapy consisted of the application MEA was performed using the Multiplate an - of 2 g tranexamic acid (Cyclocapron®, ME - alyzer and a whole blood impedance aggre - DA Pharma GmbH & Co KG, Bad Homburg, gometer (Roche AG, Grenzach, Germany) Germany) after the induction of anesthesia, based on the impedance aggregometry de - and another 2 g was added into the priming scribed by Cardinal and Flower [11]. The de - volume of the heart-lung machine and again vice has five test cells for parallel testing, and during CPB. Extracorporeal circulation was each test cell incorporates two independent performed in mild hypothermia. When sur - sensor units. The analysis is based on the ag - gery was completed, patients were re - gregation of the activated platelets onto met - warmed to 36°C and weaned from CPB. To al sensor wires in the test cell, which increas - reverse the anticoagulant effects of heparin, es the electrical impedance between the protamine sulfate (Protaminsulfat, Novo wires. For measurement purposes, 300 mL of Nordisk Pharma GmbH, Vienna, Austria) preheated saline (37°C) and 300 mL of he - was administered, guided by the activated parin-anticoagulated whole blood were clotting time (ACT). If the target ACT was not placed into the test cell, and the sample was obtained despite repeated heparin adminis - stirred using a Teflon-coated electromagnetic trations 500 to 1,000 IU of antithrombin stirrer (800 rpm) over a 3-minute incubation were infused. No procoagulatory therapy period. Platelet aggregation was initiated us - was performed before the administration of ing 0.5 mmol/L of arachidonic acid (ASPItest) Protamine at the end of CPB. with commercially available reagents. The in - creased impedance due to the attachment of platelets to the electrodes was continuously Hematological Analyses and separately measured by each sensor unit At each measuring point, we performed MEA for 6 minutes. The data were transformed in - analyses, blood gas analyses and conven - to arbitrary aggregation units and plotted as tional coagulation analyses. Preoperatively, two separate aggregation curves against time. blood samples were drawn by a single ve - The platelet aggregation in each test was nous puncture with a 21G butterfly needle quantified by the area under the aggregation (Safety-Multifly ® Set, Sarstedt AG&Co., Nüm - curve (AUC), which was given in arbitrary brecht, Germany). Postoperatively, blood units called “aggregation units” (U). Standard was drawn using the intraoperatively placed quality