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Association of Histones With Coagulofibrinolytic Responses and Organ Dysfunction in Adult Post-cardiac Arrest Syndrome

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Title: Association of Histones With Coagulofibrinolytic Responses and Organ Dysfunction in Adult Post-cardiac Arrest Syndrome
Authors: Mizugaki, Asumi Browse this author
Wada, Takeshi Browse this author →KAKEN DB
Tsuchida, Takumi Browse this author
Gando, Satoshi Browse this author →KAKEN DB
Keywords: histone
disseminated intravascular coagulation
post-cardiac arrest syndrome
coagulation
fibrinolysis
multiple organ dysfunction syndrome
Issue Date: 28-Jun-2022
Publisher: Frontiers Media
Journal Title: Frontiers in Cardiovascular Medicine
Volume: 9
Start Page: 885406
Publisher DOI: 10.3389/fcvm.2022.885406
Abstract: BackgroundPatients successfully resuscitated from cardiac arrest often develop organ dysfunction caused by systemic inflammation and increased coagulation, leading to disseminated intravascular coagulation (DIC). The involvement of histones in DIC and organ dysfunction in patients with sepsis and trauma has been previously reported, raising the probability that histones may also be associated with pathophysiology in patients after cardiac arrest and resuscitation. This study evaluated the relationship between histones and organ dysfunction related to coagulofibrinolytic changes in patients with post-cardiac arrest syndrome (PCAS). MethodsThis prospective single-center observational study assessed 35 adult patients with PCAS who were divided into two groups, i.e., 15 patients with multiple organ dysfunction syndrome (MODS) and 20 patients without MODS. MODS was defined as a sequential organ failure assessment score of >= 12. The plasma levels of histones and coagulofibrinolytic markers, including soluble fibrin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, plasmin-alpha 2-plasmin inhibitor complex (PIC), and soluble thrombomodulin, were measured in patients with PCAS immediately after admission to the emergency department, and 3 and 24 h after arriving at the hospital. ResultsPCAS patients with MODS had higher DIC scores [4 (3.0-5.0) vs. 1 (0.0-3.0), p = 0.012] and higher mortality rates (66.7% vs. 20.0%, p = 0.013) than those without MODS. Moreover, patients with MODS exhibited higher histone levels than those without MODS during the early phase of the post-resuscitation period. Severe endothelial injury and higher thrombin and plasmin generation were observed in the MODS group. Plasma levels of histones were positively correlated with those of soluble fibrin immediately after resuscitation (rho = 0.367, p = 0.030) and PIC 3 h after arriving at the hospital (rho = 0.480, p = 0.005). This correlation was prominent in the patient population with MODS (soluble fibrin: rho = 0.681, p = 0.005, PIC: rho = 0.742, p = 0.002). ConclusionsThis study demonstrated that elevated histone levels were associated with increased levels of thrombin, and subsequent plasmin generation in PCAS patients, especially those with MODS. Further studies are required to elucidate the causal relationship between histones and organ dysfunction related to DIC in PCAS.
Type: article
URI: http://hdl.handle.net/2115/86791
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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