scholarly journals Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Thomas Scherz ◽  
Thomas M. Hofbauer ◽  
Anna S. Ondracek ◽  
Daniel Simon ◽  
Fritz Sterz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Therapeutic Hypothermia ◽  
Platelet Reactivity ◽  
Mild Therapeutic Hypothermia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Bleeding Events ◽  
Platelet Aggregometry ◽  
Elisa Testing ◽  
Plasmatic Coagulation

Background and Rationale: Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients.Methods and Results: Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times.Conclusion: Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.

scholarly journals Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction

2021 ◽  
Vol 8 (10) ◽  
pp. 131
Author(s):  
Matthias Mueller ◽  
Dietrich Beitzke ◽  
Thomas Scherz ◽  
Christian Loewe ◽  
Andreas Mangold ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Hospital Admission ◽  
Infarct Size ◽  
Therapeutic Hypothermia ◽  
Surrogate Marker ◽  
Left Ventricular ◽  
Mild Therapeutic Hypothermia ◽  
St Segment Elevation ◽  
Segment Elevation Myocardial Infarction ◽  
St Segment

Background: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin―a surrogate marker for vasopressin―is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin levels have not been investigated in MTH during STEMI. Methods: We analyzed patients treated with MTH during STEMI in a sub-study of the STATIM trial (Testori, Heart 2019). Patients were randomized to normothermia or MTH with out-of-hospital initiation. Seven copeptin samples were collected from each patient. Primary endpoint was the difference in copeptin levels between the groups. As secondary endpoints, we defined differences in the kinetics between the sampling timepoints and the correlation between copeptin and the infarct size in relation to left ventricular myocardium. Results: We included 99 patients (MTH n = 47, control n = 52) in our intention to treat analysis. No differences in copeptin values at first medical contact between the MTH and normothermia groups were found. MTH showed no effect on copeptin levels, neither during cooling phase nor through the course. Copeptin peaked at first medical contact and hospital admission in both groups. No differences in kinetics between the timepoints were found. Copeptin showed no correlation with infarct size, neither at first medical contact nor hospital admission. Conclusions: Copeptin levels were not influenced by MTH in STEMI, suggesting the use of this biomarker also during temperature management. Furthermore, copeptin levels were not usable as a surrogate marker for infarct size at any timepoint.

Abstract 17314: Impact of Mild Therapeutic Hypothermia on Platelet Inhibition in Acute Coronary Syndrome

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jan Kaufmann ◽  
Helena Stockmann ◽  
Philipp Stawowy ◽  
Kristof Graf ◽  
Eckart Fleck ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Antiplatelet Therapy ◽  
Therapeutic Hypothermia ◽  
Platelet Function ◽  
Mild Hypothermia ◽  
Plasma Concentrations ◽  
Mild Therapeutic Hypothermia ◽  
Light Transmittance ◽  
Coronary Syndrome ◽  
Platelet Aggregometry

Background: Mild therapeutic hypothermia (MTH) improves outcome for patients with acute coronary syndrome (ACS) after cardiac arrest (CA). Previous data point to an interaction between hypothermia and drug metabolism, thus potentially impacting on platelet function under antiplatelet therapy. Purpose: The aim of the study is to determine clopidogrel metabolism and platelet function in clopidogrel naïve ACS patients treated with mild hypothermia (33°C, n=12) compared with ACS patients (troponin positive) with normal body temperature (n=14). Methods: Platelet function was measured by light transmittance aggregometry (LTA), multiple electrode platelet aggregometry (MEA) and VASP phosphorylation analysis before, 2h, 4h and 24h after administration of a 600 mg clopidogrel loading dose. Furthermore, plasma concentrations of clopidogrel, the active thiol metabolite and the inactive carboxyl metabolite were determined. All patients were screened for CYP2C19*2 polymorphism and scheduled for PCI. Mild hypothermia was carried out according to current guidelines for 24 hours at a target temperature of 33°C. Results: Plasma concentration of clopidogrel and metabolites were lower in the MTH group after 2h and 4h, respectively (all p<0.005). All platelet function tests showed an attenuated response to clopidogrel with respect to baseline platelet activity in the MTH group. This was significant for VASP analysis and LTA (p<0.05). Moreover, there was no difference in genotype and platelet function determined ex vivo with 33°C and 37°C, respectively. Conclusion: Inhibition of platelet function is decreased under MTH, presumably due to a diminished clopidogrel absorption and metabolization. Thus, these patients might have a higher risk for cardiovascular events despite antiplatelet therapy.

scholarly journals ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
C Scherer ◽  
E Luesebrink ◽  
S Massberg ◽  
D Sibbing ◽  
M Orban
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Platelet Aggregation ◽  
Cardiogenic Shock ◽  
Platelet Reactivity ◽  
Bleeding Risk ◽  
Left Ventricular ◽  
Severe Bleeding ◽  
Bleeding Events ◽  
Significant Difference

Abstract Funding Acknowledgements Type of funding sources: None. Background While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock (CS). Methods The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) and with available on-treatment ADP-induced platelet aggregation measurements. Results Out of 233 patients, 74 suffered from a severe BARC 3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (10 AU [IQR 3 - 13] vs. 15 AU [IQR 9 - 25], p &lt; 0.001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU, 95% confidence interval (CI) 0.942-0.994). An optimal cut-off value of &lt;12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, use of VA-ECMO (HR 1.972, 95% CI 1.003-3.879) or coaxial left ventricular pump (HR 2.593, 95% CI 1.509-4.455), first lactate (HR 1.093 per mmol/l, 95% CI 1.037-1.152) and thrombocyte count (HR 0.994 per G/l, 95% CI 0.990-0.998) were independent predictors of BARC≥3 bleedings. There was no significant difference in survival nor ischemic events between patients with low and high on-treatment platelet reactivity. Conclusion: Lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in CS warrants further investigation.

Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation

2016 ◽  
Vol 115 (05) ◽  
pp. 960-968 ◽  
Author(s):  
Ulrike Flierl ◽  
Philipp Röntgen ◽  
Zauner Florian ◽  
Tongers Jörn ◽  
Berliner Dominik ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Therapeutic Hypothermia ◽  
Gastric Tube ◽  
Therapeutic Strategy ◽  
Platelet Reactivity ◽  
Platelet Inhibition ◽  
Reactivity Index ◽  
Vasopressor Use ◽  
Hospital Cardiac Arrest

SummaryAcute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours(h) following a loading dose of 60 mg via a gastric tube. Mean PRI (±SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition.

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