Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential

Ito, Takashi; Thachil, Jecko; Asakura, Hitoshi; Levy, Jerrold H.; Iba, Toshiaki

doi:10.1186/s13054-019-2552-0

Cited by 92 publications

(95 citation statements)

References 100 publications

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“…However, studies are ongoing to evaluate other potential molecules in patients with sepsis induced coagulopathy or DIC. The preliminary success of recombinant soluble thrombomodulin in DIC and clinical states associated with endothelial dysfunction has shown promise with its tolerable side effect profile [37]. SARS CoV-2 enters the pulmonary epithelium by binding to ACE2; ACE2 in turn is cleaved and activated by host transmembrane serine protease 2 (TMPRSS2).…”

Section: Anticoagulant Use: Where Do We Stand?mentioning

confidence: 99%

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate

2020

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has emerged as a pandemic, claiming over 350,000 lives worldwide. Disease mortality has been mostly attributed to viral pneumonia, complicated by acute respiratory distress syndrome (ARDS) and/or sepsis. A cytokine storm like picture in peripheral blood, as evident by significantly higher plasma levels of interleukin (IL)-2, IL-7, tumor necrosis factor-α (TNF-α), granulocyte colonystimulating factor (GCSF), monocyte chemoattractant protein-1 (MCP-1), inducible protein 10 (IP 10) and macrophage inflammatory protein 1-α (MIP-1α), has been shown in severe COVID-19 illness [1]. Albeit uncommon, but biochemical findings like C-reactive protein, D-dimer, liver enzymes and ferritin in high concentration along with increase in IL-6, IL-10 and interferon (IFN)-γ are being reported in critically ill children with COVID-19 [2]. This points towards a coexistence of possible secondary hemophagocytic

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Section: Anticoagulant Use: Where Do We Stand?mentioning

confidence: 99%

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate

2020

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“…The effect of recombinant thrombomodulin administration in sepsis-induced coagulopathy in the SCARLET study [21] was not statistically signi cant. However, a post hoc analysis revealed a 5.4% reduction in absolute mortality among patients who ful lled the entry criterion at baseline [28]. Although no signi cant differences in the TM-α dose or the period of administration were seen between these two states in both types of DIC, the 28-day survival rate and resolution rate according to JMHW, ISTH or JAAM diagnostic criteria in infectious-type DIC with hypo brinogenemia were signi cantly lower than in infectious-type DIC without hypo brinogenemia; this was only observed in infectious-type DIC.…”

Section: Discussionmentioning

confidence: 95%

Hypofibrinogenemia is Associated With a High Degree of Risk in Infectious and Hematological Diseases: A Post-Hoc Analysis of Post-Marketing Surveillance of Patients With Disseminated Intravascular Coagulation Treated With Thrombomodulin Alfa

Kawasugi

Wada

Honda

et al. 2020

Preprint

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Introduction In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value and the relationship between hypofibrinogenemia and the outcomes of infectious DIC has remained unclear.Materials and Methods We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for with DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level of <1.5 g/L.Results Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly high in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower in infectious disease patients with DIC with hypofibrinogenemia than in those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.Conclusion In infectious disease patients with DIC, hypofibrinogenemia may reflect from the increased consumption of fibrinogen due to an accelerated coagulating reaction, while that in hematological disease patients DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

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“…The clinical use of recombinant TM has been tested, and although theoretically promising, it has not been associated with a significant reduction in mortality or other secondary outcomes when compared to placebo to date[ 2 , 34 , 46 , 47 ]. Rhodes et al[ 48 ] recommended not using antithrombin due to a lack of evidence of an effect.…”

Section: Discussionmentioning

confidence: 99%

Association between thrombomodulin and high mobility group box 1 in sepsis patients

Rodrigues¹,

Rodrigues²,

Rodrigues³

et al. 2020

WJCCM

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BACKGROUND High mobility group box 1 (HMGB1) has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin (TM) seems to decrease HMGB1 activity. AIM To investigate the role of the thrombomodulin/high mobility group box 1 (T/H) ratio in patients with sepsis and their association with their clinic, testing the hypothesis that higher ratios are associated with better outcomes. METHODS Twenty patients diagnosed with sepsis or septic shock, according to the 2016 criteria sepsis and septic shock (Sepsis-3), were studied. Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization (D28). The following clinical outcomes were observed: Sequential Organ Failure Assessment (SOFA) score; Need for mechanical pulmonary ventilation; Presence of septic shock; Occurrence of sepsis-induced coagulopathy; Need for renal replacement therapy (RRT); and Death. RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM: 76.41 ± 29.21 pg/mL vs 37.41 ± 22.55 pg/mL among those whose SOFA scores were less than 12 points, P = 0.003. The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points, P = 0.001. The T/H ratio was, on average, three times higher in patients in need of RRT (0.38 ± 0.14 vs 0.11 ± 0.09), P < 0.001. CONCLUSION Higher serum levels of TM and, therefore, higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy, while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.

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Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential

Cited by 92 publications

References 100 publications

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate

COVID-19 Associated Hemophagocytic Lymphohistiocytosis and Coagulopathy: Targeting the Duumvirate

Hypofibrinogenemia is Associated With a High Degree of Risk in Infectious and Hematological Diseases: A Post-Hoc Analysis of Post-Marketing Surveillance of Patients With Disseminated Intravascular Coagulation Treated With Thrombomodulin Alfa

Association between thrombomodulin and high mobility group box 1 in sepsis patients

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