Larsen Julie Brogaard, Pihl Rasmus, Aggerbeck Mathies Appel, Larsen Kim Michael, Hvas Christine Lodberg, Johnsen Nanna, Christensen Mette G, Praetorius Helle, Hvas Anne-Mette, Thiel Steffen
Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Res Pract Thromb Haemost. 2023 Feb 8;7(2):100078. doi: 10.1016/j.rpth.2023.100078. eCollection 2023 Feb.
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.
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.
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 sepsis model.
ITIH4 did not display acute-phase behavior as mean ITIH4 levels were not increased in patients with septic shock or in -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, = .01), low antithrombin ( = 0.70, < .0001) and decreased thrombin generation (mean ITIH4: first peak thrombin tertile, 210 μg/mL vs third peak thrombin tertile, 303 μg/mL, = .01). ITIH4 showed moderate correlation with arterial blood lactate (ρ = -0.50, < .001) but only weak correlations with C-reactive protein, alanine transaminase, bilirubin, and Sequential Organ Failure Assessment score (all, ρ < 0.26, > .05).
ITIH4 is associated with sepsis-related coagulopathy but is not an acute-phase reactant during septic shock.
蛋白酶抑制剂α-抑制因子重链H4（ITIH4）已被描述为一种急性期反应物，可能有助于脓毒症的监测和预后评估。
比较脓毒症患者与健康对照者的ITIH4血浆水平，并研究ITIH4与脓毒症急性期反应标志物、凝血及器官功能障碍之间的关联。
我们对一项前瞻性队列研究进行了事后分析。脓毒性休克患者（n = 39）在入住重症监护病房时入组。采用内部免疫分析法检测ITIH4。记录标准凝血参数、凝血酶生成、纤维蛋白形成和溶解、C反应蛋白、器官功能障碍标志物、序贯器官衰竭评估评分及弥散性血管内凝血（DIC）评分。还在小鼠脓毒症模型中研究了ITIH4水平。
ITIH4未表现出急性期行为，因为脓毒性休克患者或感染小鼠的平均ITIH4水平未升高。然而，与健康对照者相比，脓毒性休克患者的ITIH4存在较大的个体间差异。低ITIH4与脓毒症相关凝血病有关，包括高DIC评分（平均ITIH4：DIC组为203μg/mL，非DIC组为267μg/mL，P = 0.01）、低抗凝血酶（r = 0.7 ⁇ ，P < 0.0001）及凝血酶生成减少（平均ITIH4：凝血酶第一峰三分位数组为210μg/mL，凝血酶第三峰三分位数组为303μg/mL，P = 0.01）。ITIH4与动脉血乳酸呈中度相关（ρ = -0.50，P < 0.001），但与C反应蛋白、丙氨酸转氨酶、胆红素及序贯器官衰竭评估评分仅呈弱相关（均为ρ < 0.26，P > 0.05）。
ITIH4与脓毒症相关凝血病有关，但在脓毒性休克期间不是急性期反应物。
