Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation - A meta-analysis

Kato, Hideo; Hagihara, Mao; Asai, Nobuhiro; Umemura, Takumi; Hirai, Jun; Môri, N.; Yamagishi, Yuka; Iwamoto, Takuya; Mikamo, Hiroshige

doi:10.1016/j.thromres.2023.05.009

Cited by 7 publications

(2 citation statements)

References 36 publications

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“… 37 , 38 It is worth noting that recombinant human thrombomodulin has been shown to effectively reduce mortality rates in patients with sepsis‐induced disseminated intravascular coagulation without elevating bleeding risk. 39 Therefore, it is of great clinical significance to further investigate the predictive effect of sTM, the rate of thrombomodulin shedding, and the potential of recombinant human thrombomodulin as a suitable treatment modality for patients with AIS.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke

Xu,

Song,

Cao

et al. 2024

JAHA

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Background This study aimed to investigate regional levels of TAT (thrombin‐antithrombin complex), PIC (plasmin‐α2 plasmin inhibitor complex), t‐PAIC (tissue plasminogen activator‐plasminogen activator inhibitor complex), sTM (soluble thrombomodulin), and D‐dimer, along with their associations with clinical and procedural characteristics in patients with acute ischemic stroke undergoing endovascular thrombectomy. Methods and Results We retrospectively analyzed 166 consecutive patients with acute ischemic stroke (62±11.54 years of age, 34.3% women) using prospectively maintained clinical databases and blood samples from local ischemic (proximal to thrombus) and systemic (femoral artery, self‐control) arterial compartments. Levels of TAT, PIC, t‐PAIC, and D‐dimer were significantly elevated, whereas sTM was significantly reduced, in local ischemic regions compared with their systemic levels. Each 1‐unit increase in ischemic TAT (adjusted odds ratio [aOR], 1.086 [95% CI, 1.03–1.145]; P =0.002; area under the curve [AUC], 0.833) and PIC (aOR, 1.337 [95% CI, 1.087–1.644]; P =0.006; AUC, 0.771) correlated significantly with higher symptomatic intracranial hemorrhage risk. Additionally, each 1‐unit increase in ischemic TAT (aOR, 1.076 [95% CI, 1.016–1.139]; P =0.013; AUC, 0.797), PIC (aOR, 1.554 [95% CI, 1.194–2.022]; P =0.001; AUC, 0.798), and sTM (aOR, 0.769 [95% CI, 0.615–0.961]; P =0.021; AUC, 0.756) was significantly associated with an increased risk of an unfavorable 90‐day outcome (modified Rankin scale of 3–6). These hemostatic molecules, individually or combined, significantly improved the predictive power of conventional risk factors, as evidenced by significant increases in net reclassification improvement and integrated discrimination improvement (all P <0.01). Conclusions We observed a hyperactive state of the coagulation‐fibrinolysis system within the local ischemic region during hyperacute stroke. Rapid automated measurement of hemostatic molecular markers, particularly TAT, PIC, and sTM, during intra‐arterial procedures may provide additional information for stroke risk stratification and therapeutic decision‐making, and warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke

Xu,

Song,

Cao

et al. 2024

JAHA

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“…The activation of the coagulation system during sepsis strongly associates with organ dysfunction and hemorrhage ( Iba et al, 2019 ; Iba et al, 2020 ). In addition, a recombinant human soluble thrombomodulin reduced mortality in patients with sepsis-induced DIC without increasing the bleeding risk during the treatment ( Kato et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway

Peng,

Lv,

Wang

et al. 2023

Front. Pharmacol.

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Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.

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Koagulopathien

Liakopoulos

2024

Springer Reference Medizin

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Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation - A meta-analysis

Cited by 7 publications

References 36 publications

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke

Alterations of Hemostatic Molecular Markers During Acute Large Vessel Occlusion Stroke

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway

Koagulopathien

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