Heatstroke-induced coagulopathy: Biomarkers, mechanistic insights, and patient management

Iba, Toshiaki; Connors, Jean M.; Levi, Marcel; Levy, Jerrold H.

doi:10.1016/j.eclinm.2022.101276

Cited by 34 publications

(43 citation statements)

References 71 publications

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“…It is well-known that HS triggers major changes in blood biochemical parameters, systemic inflammation, and coagulopathy [38][39][40]. Following HS, many intracellular com-ponents were released into the blood flow; among others, high levels of CK, LDH and AST are commonly detected in patients with HS [41,42].…”

Section: Discussionmentioning

confidence: 99%

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Parte

Rodrigo

Gutiérrez-Basoa

et al. 2022

Cancers

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Background: Lately, major advances in crucial aspects of magnetic hyperthermia (MH) therapy have been made (nanoparticle synthesis, biosafety, etc.). However, there is one key point still lacking improvement: the magnetic field-frequency product (H × f = 4.85 × 108 Am−1s−1) proposed by Atkinson–Brezovich as a limit for MH therapies. Herein, we analyze both local and systemic physiological effects of overpassing this limit. Methods: Different combinations of field frequency and intensity exceeding the Atkinson–Brezovich limit (591–920 kHz, and 10.3–18 kA/m) have been applied for 21 min to WAG/RijHsd male rats, randomly distributed to groups of 12 animals; half of them were sacrificed after 12 h, and the others 10 days later. Biochemical serum analyses were performed to assess the general, hepatic, renal and/or pancreatic function. Results: MH raised liver temperature to 42.8 ± 0.4 °C. Although in five of the groups the exposure was relatively well tolerated, in the two of highest frequency (928 kHz) and intensity (18 kA/m), more than 50% of the animals died. A striking elevation in liver and systemic markers was observed after 12 h in the surviving animals, independently of the frequency and intensity used. Ten days later, liver markers were almost recovered in all of the animals. However, in those groups exposed to 591 kHz and 16 kA/m, and 700 kHz and 13.7 kA/m systemic markers remained altered. Conclusions: Exceeding the Atkinson–Brezovich limit up to 9.59 × 109 Am−1s−1 seems to be safe, though further research is needed to understand the impact of intensity and/or frequency on physiological conditions following MH.

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Section: Discussionmentioning

confidence: 99%

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Parte

Rodrigo

Gutiérrez-Basoa

et al. 2022

Cancers

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“…Hence, the increase in sCD59 does not exert a protective function against excessive complement activation. Although there are no established clinical tests that can adequately evaluate the severity of heatstroke, the platelet count, d -dimer, soluble thrombomodulin, and inflammation biomarkers such as interleukin-6 and histone H3 have been proposed as promising markers for the severity of heatstroke ( 47 ). This study raises the possibility of using sCD59 as a novel marker for the severity of heatstroke.…”

Section: Discussionmentioning

confidence: 99%

Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses

Nakamura¹,

Sueyoshi²,

Miyoshi³

et al. 2022

Critical Care Explorations

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Although multiple organ dysfunction syndrome (MODS) is the main cause of death in patients with heat-related illnesses, its underlying pathophysiological mechanism remains elusive. Complement activation is considered one of the main causes of MODS in patients with sepsis and trauma. Considering the pathophysiological similarity of heat related-illnesses with sepsis and trauma, the complement system might be activated in patients with heat-related illnesses as well. Our aim was to investigate whether excessive complement activation occurs in patients with heat-related illnesses.DESIGN: Prospective observational study. SETTING:Emergency department in the university hospital. PATIENTS:Thirty-two patients with heat-related illnesses and 15 age-matched healthy controls were enrolled in this study. INTERVENTIONS:Blood samples were collected from the study subjects for the measurement of complement factors. MEASUREMENTS AND MAIN RESULTS:Complement component 3a (C3a), complement component 5a (C5a), C5b-9, complement factor B (Ba), Factor H, and soluble CD59 in plasma were measured. The levels of C3a, C5a, C5b-9, and Ba significantly increased in patients with heat-related illnesses on day 0 compared with those in the healthy controls. Soluble CD59 was significantly high in patients with heat-related illnesses on day 0 and showed a correlation with the severity of the condition (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and staging scores), Japanese Association for Acute Medicine disseminated intravascular coagulation scores, and the coagulation system (prothrombin time and fibrin degradation products). CONCLUSIONS:The complement system was activated in patients with heatrelated illnesses, suggesting that it is one of the causes of MODS. Soluble CD59 may be a potent biomarker for the severity of heat-related illnesses.

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“…Anti-inflammatory treatment Systemic inflammation and coagulopathy are the two main factors that cause life-threatening organ dysfunction during HS [ 120 ]. The pathophysiological mechanism of HS is similar to sepsis, and systemic inflammatory reaction is important pathogenesis.…”

Section: The Treatment Strategy For Hs-induced Livermentioning

confidence: 99%

The pathogenesis and therapeutic strategies of heat stroke-induced liver injury

Wang

Zhang

et al. 2022

Crit Care

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Heat stroke (HS) is a life-threatening systemic disease characterized by an elevated core body temperature of more than 40 ℃ and subsequent multiple organ dysfunction syndrome. With the growing frequency of global heatwaves, the incidence rate of HS has increased significantly, which has caused a huge burden on people's lives and health. Liver injury is a well-documented complication of HS and usually constitutes the direct cause of patient death. In recent years, a lot of research has been carried out on the pathogenesis and treatment strategies of HS-induced liver injury. In this review, we summarized the important pathogenesis of HS-induced liver injury that has been confirmed so far. In addition to the comprehensive effect of systemic factors such as heat cytotoxicity, coagulopathy, and systemic inflammatory response syndrome, excessive hepatocyte cell pyroptosis, dysfunction of Kupffer cells, abnormal expression of heat shock protein expression, and other factors are also involved in the pathogenesis of HS-induced liver injury. Furthermore, we have also established the current therapeutic strategies for HS-induced liver injury. Our study is of great significance in promoting the understanding of the pathogenesis and treatment of HS-induced liver injury.

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Heatstroke-induced coagulopathy: Biomarkers, mechanistic insights, and patient management

Cited by 34 publications

References 71 publications

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Proposal of New Safety Limits for In Vivo Experiments of Magnetic Hyperthermia Antitumor Therapy

Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses

The pathogenesis and therapeutic strategies of heat stroke-induced liver injury

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