Influence of temperature on thromboelastometry and platelet aggregation in cardiac arrest patients undergoing targeted temperature management

Abstract

BackgroundCoagulation can be visualised using whole blood coagulation analyses such as thromboelastometry and platelet aggregation tests; however, the role of temperature in the analyses is ambiguous. The aim was to examine whether temperature influences the whole blood coagulation tests.MethodsWe included 40 patients treated with targeted temperature management (33 ± 1 °C) after out-of-hospital cardiac arrest. The blood samples were obtained on hypothermia and normothermia. Each blood sample was analysed simultaneously at 33 °C and 37 °C by thromboelastography (ROTEM®) employing the assays EXTEM®, INTEM®, FIBTEM® and HEPTEM®, and by Multiplate®Analyzer, using COLtest®, ADPtest®, ASPItest® and TRAPtest® as agonists. Data on antithrombotic drugs were collected systematically from medical records, and data were analysed using repeated measurement analysis of variance (ANOVA).ResultsThe ROTEM® analyses showed increased clotting time, lower maximum velocity and increased time to maximum velocity (all p values <0.02) when performed at 33 °C compared with 37 °C, irrespective of the patients being hypothermic (median 33.1 °C) or normothermic (median 37.5 °C). However, EXTEM® time to maximum velocity showed no difference between the analyses performed at 33 °C and 37 °C when the patients were hypothermic (p = 0.83). No differences were found in maximum clot firmness (all p values >0.09) analysed at 33 °C and 37 °C, independent of the body temperature.In the hypothermic blood sample, no difference was found when using the COLtest®, ASPItest® or TRAPtest® to compare platelet aggregation analysed at 33 °C and 37 °C (all p values >0.19), but platelet aggregation was significantly higher using the ADPtest® (p < 0.001) when analysed at 33 °C. In the normothermic blood sample, the TRAPtest® showed no difference (p = 0.73) when performed at 33 °C; however, significantly lower aggregation was found using the COLtest® and ASPItest® (all p values <0.001), while a higher aggregation at 33 °C was found using the ADPtest® (p = 0.003).ConclusionROTEM® analyses seemed not to be dependent on body temperature but showed a slower initiation of coagulation when analysed at 33 °C compared with 37 °C. The Multiplate®Analyzer results were dependent on the temperature used in the analyses and the body temperature. In whole blood coagulation tests, the temperature used in the analyses should be kept at 37 °C irrespective of the patient’s body temperature being 33 °C or 37 °C.

Adaptation of global hemostasis to therapeutic hypothermia in patients with out-of-hospital cardiac arrest: Thromboelastography study

“…Another explanation of this phenomenon may be a cold-induced decrease in bone marrow function [40]. The persistent decrease in a platelet count, which was observed in the observed group after rewarming, may also be explained by perioperative blood loss (during pPCI), which is consistent with previous studies involving invasively-treated patients [29]. TEG analysis of fibrinolysis dynamics was brought to a conclusion that one of the possible mechanisms leading to reduced clot solubility during therapeutic hypothermia is a higher secretion of tissue plasminogen activator by endothelial cells and a slower conversion of plasminogen to plasmin.…”

“…Variables resulted during both analyses were comparable [21,25,29]. The R variable, corresponding to clotting time in ROTEM ® , is the value most influenced by activity of coagulation factors.…”

Hemostasis and Thrombosis in Extreme Temperatures (Hypo- and Hyperthermia)

“…40 Platelet function was more incisively studied in a series of 82 patients undergoing therapeutic cooling after out-of-hospital cardiac arrest, which confirmed an impairment of platelet function assessed by various techniques in hypothermic patients. 41,42 Another laboratory study in 171 patients who were treated with cooling down to either 33°C or 36°C found lower platelet counts in the most intensely cold patients and thromboelastographic changes, compatible with hypocoagulability, in some patients. 43 A more precise study on coagulation function in 21 patients who were subjected to therapeutic cooling showed delayed clot formation, impaired clot stability, and enhanced endogenous fibrinolysis.…”

Post‐cardiac arrest level of free‐plasma DNA and DNA‐histone complexes

“…The study is registered in ClinicalTrails.gov (identifier: NCT02733146). Of the 42 patients included, 21 patients have previously been described by Jeppesen et al When preparing the article, the STROBE guidelines were followed.…”