Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation.
Res Pract Thromb Haemost
; 7(2): 100078, 2023 Feb.
Article
en En
| MEDLINE
| ID: mdl-36876284
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Res Pract Thromb Haemost
Año:
2023
Tipo del documento:
Article
País de afiliación:
Dinamarca