# Advances in the comprehensive mechanisms, diagnosis, and treatment of heatstroke-induced coagulopathy

**Authors:** Chuhan Xiang, Ling Gao, Xuhui Liu, Jun Xiang, Bin Zhu, Shihui Fu, Jianhui Zhao, Qing Song

PMC · DOI: 10.3389/fcell.2025.1596039 · 2025-07-15

## TL;DR

This paper reviews the causes, diagnosis, and treatment of coagulation disorders caused by heatstroke, aiming to improve management and reduce deaths.

## Contribution

The study provides a comprehensive review of HIC mechanisms, diagnostics, and therapies, emphasizing novel treatment strategies.

## Key findings

- HIC can manifest as hypocoagulopathy or hypercoagulopathy, significantly contributing to heatstroke mortality.
- Current treatments include replacement therapy, anticoagulants, traditional Chinese medicine, and novel approaches.
- The paper highlights the need for better understanding of HIC pathophysiology and targeted pharmacological interventions.

## Abstract

Heatstroke (HS) is a life-threatening condition that is precipitated by heat stress. The coagulation disorder that consequentially develops is termed heatstroke-induced coagulopathy (HIC). HIC typically presents as either hypocoagulopathy or hypercoagulopathy and is a principal complication that contributes to HS-associated mortality. There is no current consensus regarding HIC pathophysiology and specific pharmacological treatments. We review the diagnostic approaches, underlying mechanisms, and therapeutic interventions for HIC, with a particular emphasis on pharmacological treatments that include replacement therapy, anticoagulant therapy, traditional Chinese medicine, and novel therapies. The aim of this study is to enhance HIC awareness among clinicians and researchers and discuss the latest treatment strategy advancements to ultimately facilitate comprehensive HIC management and reduce its mortality rate.

## Full-text entities

- **Genes:** Dnase1 (deoxyribonuclease I) [NCBI Gene 13419] {aka DNaseI, Dnl1}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, SELP (selectin P) [NCBI Gene 6403] {aka CD62, CD62P, GMP140, GRMP, LECAM3, PADGEM}, THPO (thrombopoietin) [NCBI Gene 7066] {aka CAMT2, MGDF, MKCSF, ML, MPLLG, THC9}, CREBBP (CREB binding lysine acetyltransferase) [NCBI Gene 1387] {aka CBP, KAT3A, MKHK1, RSTS, RSTS1}, PROC (protein C, inactivator of coagulation factors Va and VIIIa) [NCBI Gene 5624] {aka APC, PC, PROC1, THPH3, THPH4}, Selplg (selectin, platelet (p-selectin) ligand) [NCBI Gene 20345] {aka CD162, Psgl-1, Psgl1, Selp1, Selpl}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, Fga (fibrinogen alpha chain) [NCBI Gene 14161] {aka Fib}, THBD (thrombomodulin) [NCBI Gene 7056] {aka AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, F2 (coagulation factor II) [NCBI Gene 14061] {aka Cf-2, Cf2, FII}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, GDNF (glial cell derived neurotrophic factor) [NCBI Gene 2668] {aka ATF, ATF1, ATF2, HFB1-GDNF, HSCR3}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, Vwf (Von Willebrand factor) [NCBI Gene 22371] {aka 6820430P06Rik, B130011O06Rik, C630030D09, F8VWF, VWD}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, Selp (selectin, platelet) [NCBI Gene 20344] {aka CD62P, GMP-140, Grmp, LECAM3, PADGEM}, F12 (coagulation factor XII) [NCBI Gene 2161] {aka HAE3, HAEX, HAF}, SERPINC1 (serpin family C member 1) [NCBI Gene 462] {aka AT3, AT3D, ATIII, ATIII-R2, ATIII-T1, ATIII-T2}, IL11 (interleukin 11) [NCBI Gene 3589] {aka AGIF, IL-11}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, F7 (coagulation factor VII) [NCBI Gene 2155] {aka SPCA}, PF4 (platelet factor 4) [NCBI Gene 5196] {aka CXCL4, PF-4, SCYB4}, Itpr3 (inositol 1,4,5-triphosphate receptor 3) [NCBI Gene 16440] {aka IP3R 3, IP3R-3, Ip3r3, Itpr-3, tf}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, F2R (coagulation factor II thrombin receptor) [NCBI Gene 2149] {aka CF2R, HTR, PAR-1, PAR1, TR}, F10 (coagulation factor X) [NCBI Gene 2159] {aka FX, FXA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD34 (CD34 molecule) [NCBI Gene 947]
- **Diseases:** hemorrhagic shock (MESH:D012771), cerebral ischemic damage (MESH:D002539), NETs (MESH:C536657), ischemic damage (MESH:D017202), circulatory failure (MESH:D012769), hypercoagulability (MESH:D019851), PT (MESH:D007020), hypofibrinogenemia (MESH:D000347), hypothermia (MESH:D007035), necrosis (MESH:D009336), hypocalcemia (MESH:D006996), death (MESH:D003643), Sepsis (MESH:D018805), hemophilia A or B (MESH:D002836), Thrombosis and Haemostasis (MESH:D020141), inflammation (MESH:D007249), arterial hypotension (MESH:D007022), tumor (MESH:D009369), liver failure (MESH:D017093), congenital factor VII deficiency (MESH:D005168), thrombocytopenia (MESH:D013921), infectious diseases (MESH:D003141), EHS (MESH:D018883), gastrointestinal hemorrhage (MESH:D006471), Coagulopathy (MESH:D001778), AT (MESH:D020152), acidosis (MESH:D000138), endotoxemia (MESH:D019446), ISTH (MESH:C000719191), fever (MESH:D005334), hepatic, renal injury (MESH:D058186), leukocytosis (MESH:D007964), Glanzmann's thrombasthenia (MESH:D013915), cerebral ischemia (MESH:D002545), HIT (MESH:C562865), DIC (MESH:D004211), hemophilia (MESH:D006467), damage (MESH:D020263), deep vein thrombosis (MESH:D020246), multiple organ dysfunction syndrome (MESH:D009102), septic (MESH:D001170), platelet aggregation (MESH:D001791), cytotoxic (MESH:D064420), nervous system injuries (MESH:D020196), hypoxia (MESH:D000860), ischemic cardiomyopathy (MESH:D009202), kidney function damage (MESH:D007674), bleeding (MESH:D006470), venous thrombi (MESH:D014647), Thrombosis (MESH:D013927), prolonged (MESH:D008133)
- **Chemicals:** heparan sulfate (MESH:D006497), bilirubin (MESH:D001663), Heparin (MESH:D006493), LMWH (MESH:D006495), water (MESH:D014867), argatroban (MESH:C031942), adenosine diphosphate (MESH:D000244), nitric oxide (MESH:D009569), sulfated glycosaminoglycan (MESH:C013786), CTC-111 (-), tranexamic acid (MESH:D014148), D (MESH:D003903), heme (MESH:D006418)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12303890/full.md

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Source: https://tomesphere.com/paper/PMC12303890