Inter-α-inhibitor heavy chain H4 and sepsis-related coagulation disturbances: Another link between innate immunity and coagulation Journal Article
| Authors: | 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. |
| Article 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. © 2023 The Authors |
| Keywords: | adult; controlled study; aged; unclassified drug; mortality; nonhuman; prospective study; c reactive protein; mouse; cohort analysis; alanine aminotransferase; bilirubin; intensive care unit; disease severity; blood sampling; escherichia coli; western blotting; sepsis; innate immunity; immunoassay; leukocyte count; inferior cava vein; blood clotting disorder; centrifugation; bilirubin blood level; proteinase inhibitor; freeze thawing; murine model; resuscitation; fibrinogen; fibrinogen blood level; multiple organ failure; platelet count; low molecular weight heparin; thrombin; noradrenalin; ketamine; d dimer; dalteparin; mean arterial pressure; fluorometry; fibrin; blood clotting; lactate blood level; septic shock; antithrombin; thrombosis prevention; fluid resuscitation; disseminated intravascular coagulation; bacterial load; antivitamin k; acute-phase reaction; activated partial thromboplastin time; disseminated intravascular clotting; acute phase protein; heavy chain; prognosis; human; male; female; article; fluid balance; sequential organ failure assessment score; xylazine; itih4 protein, human; inter alpha inhibitor heavy chain h4; thrombocyte poor plasma |
| Journal Title: | Research and Practice in Thrombosis and Haemostasis |
| Volume: | 7 |
| Issue: | 2 |
| ISSN: | 2475-0379 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-02-01 |
| Start Page: | 100078 |
| Language: | English |
| DOI: | 10.1016/j.rpth.2023.100078 |
| PROVIDER: | scopus |
| PMCID: | PMC9974438 |
| PUBMED: | 36876284 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2023 -- Source: Scopus |
