Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

Julie Brogaard Larsen; Rasmus Pihl; Mathies Appel Aggerbeck; Kim Michael Larsen; Christine Lodberg Hvas; Nanna Johnsen; Mette G Christensen; Helle Praetorius; Anne-Mette Hvas; Steffen Thiel

doi:10.1016/j.rpth.2023.100078

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

Julie Brogaard Larsen^*, Rasmus Pihl, Mathies Appel Aggerbeck, Kim Michael Larsen, Christine Lodberg Hvas, Nanna Johnsen, Mette G Christensen, Helle Praetorius, Anne-Mette Hvas, Steffen Thiel

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.

OBJECTIVES: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.

METHODS: We performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model.

RESULTS: ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin ( r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05).

CONCLUSION: ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

Originalsprog	Engelsk
Artikelnummer	100078
Tidsskrift	Research and Practice in Thrombosis and Haemostasis
Vol/bind	7
Nummer	2
DOI	https://doi.org/10.1016/j.rpth.2023.100078
Status	Udgivet - feb. 2023

Adgang til dokumentet

10.1016/j.rpth.2023.100078Licens: CC BY-NC-ND

Citationsformater

Larsen, J. B., Pihl, R., Aggerbeck, M. A., Larsen, K. M., Hvas, C. L., Johnsen, N., Christensen, M. G., Praetorius, H., Hvas, A.-M., & Thiel, S. (2023). Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation. Research and Practice in Thrombosis and Haemostasis, 7(2), Artikel 100078. https://doi.org/10.1016/j.rpth.2023.100078

@article{122bf8036b5d4f00825694d0c2f8fab8,

title = "Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation",

abstract = "BACKGROUND: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.OBJECTIVES: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.METHODS: We performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model. RESULTS: ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin ( r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05). CONCLUSION: ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.",

keywords = "Acute-phase reaction, ITIH4 protein, human, disseminated intravascular coagulation, multiple organ failure, prognosis, sepsis",

author = "Larsen, {Julie Brogaard} and Rasmus Pihl and Aggerbeck, {Mathies Appel} and Larsen, {Kim Michael} and Hvas, {Christine Lodberg} and Nanna Johnsen and Christensen, {Mette G} and Helle Praetorius and Anne-Mette Hvas and Steffen Thiel",

note = "{\textcopyright} 2023 The Authors.",

year = "2023",

month = feb,

doi = "10.1016/j.rpth.2023.100078",

language = "English",

volume = "7",

journal = "Research and Practice in Thrombosis and Haemostasis",

issn = "2475-0379",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "2",

}

Larsen, JB, Pihl, R, Aggerbeck, MA, Larsen, KM, Hvas, CL , Johnsen, N , Christensen, MG , Praetorius, H , Hvas, A-M & Thiel, S 2023, 'Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation', Research and Practice in Thrombosis and Haemostasis, bind 7, nr. 2, 100078. https://doi.org/10.1016/j.rpth.2023.100078

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation. / Larsen, Julie Brogaard; Pihl, Rasmus; Aggerbeck, Mathies Appel et al.
I: Research and Practice in Thrombosis and Haemostasis, Bind 7, Nr. 2, 100078, 02.2023.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances

T2 - Another link between innate immunity and coagulation

AU - Larsen, Julie Brogaard

AU - Pihl, Rasmus

AU - Aggerbeck, Mathies Appel

AU - Larsen, Kim Michael

AU - Hvas, Christine Lodberg

AU - Johnsen, Nanna

AU - Christensen, Mette G

AU - Praetorius, Helle

AU - Hvas, Anne-Mette

AU - Thiel, Steffen

PY - 2023/2

Y1 - 2023/2

N2 - BACKGROUND: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.OBJECTIVES: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.METHODS: We performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model. RESULTS: ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin ( r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05). CONCLUSION: ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

AB - BACKGROUND: The protease inhibitor inter-α-inhibitor heavy chain H4 (ITIH4) has been described as an acute-phase reactant and could potentially aid in sepsis monitoring and prognostication.OBJECTIVES: To investigate ITIH4 plasma levels in sepsis patients compared with healthy controls and to examine the association between ITIH4 and acute-phase response markers, blood coagulation, and organ dysfunction in sepsis.METHODS: We performed a post hoc study to a prospective cohort study. Patients with septic shock (n = 39) were enrolled upon intensive care unit admission. ITIH4 was analyzed using an in-house immunoassay. Standard coagulation parameters, thrombin generation, fibrin formation and lysis, C-reactive protein, organ dysfunction markers, Sequential Organ Failure Assessment score, and disseminated intravascular coagulation (DIC) score were registered. ITIH4 levels were also investigated in a murine Escherichia coli sepsis model. RESULTS: ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in E. coli-infected mice. However, ITIH4 exhibited large interindividual variation in patients with septic shock compared with healthy controls. Low ITIH4 was associated with sepsis-related coagulopathy, including a high DIC score (mean ITIH4: DIC, 203 μg/mL vs non-DIC, 267 μg/mL, P = .01), low antithrombin ( r = 0.70, P < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, P = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, P < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, P > .05). CONCLUSION: ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.

KW - Acute-phase reaction

KW - ITIH4 protein, human

KW - disseminated intravascular coagulation

KW - multiple organ failure

KW - prognosis

KW - sepsis

U2 - 10.1016/j.rpth.2023.100078

DO - 10.1016/j.rpth.2023.100078

M3 - Journal article

C2 - 36876284

SN - 2475-0379

VL - 7

JO - Research and Practice in Thrombosis and Haemostasis

JF - Research and Practice in Thrombosis and Haemostasis

IS - 2

M1 - 100078

ER -

Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater