Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery

Later, Alexander F.L.; Sitniakowsky, L.S.; Hilten, J. A. van; Watering, Leo van de; Brand, Anneke; Smit, Nico P.M.; Klautz, Robert J.M.

doi:10.1016/j.jtcvs.2012.11.042

Cited by 44 publications

(48 citation statements)

References 27 publications

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“…A meta-analysis of randomized controlled trials also suggested the ulinastatin could significantly reduce the cytokine concentrations in patients undergoing cardiac surgery compared with those who received placebo (32). Compared with ulinastatin, aprotinin, a serine protease inhibitor derived from bovine lung tissue which has antifibrinolyticand anti-inflammatory effects (41), was mainly used to reduce perioperative bleeding and transfusion in cardiac surgery (42), but its renoprotectiverole is still controversial (43-45). In addition, the protective role of ulinastatin was also confirmed by a propensity score matched study (46).…”

Section: Discussionmentioning

confidence: 99%

Reassessment of Acute Kidney Injury after Cardiac Surgery: A Retrospective Study

Xie

Wan

et al. 2017

Intern. Med.

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Objective To evaluate the incidence, risk, or protective factors of acute kidney injury (AKI) in patients after cardiac surgery based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective analysis of 2,575 patients undergoing their first documented cardiac surgery with cardiopulmonary bypass (CPB) was conducted. Perioperative variables were collected and analyzed. Univariate and multiple logistic regression models were used for determining the association between the development of AKI and risk factors. Multiple Cox-proportional hazards modeling was performed to evaluate the impact of AKI on the mortality in the intensive care unit and hospital length of stay. Results Of 2,575 patients, 931 (36%) developed AKI. A total of 30 (1.2%) patients required renal replacement therapy. In the multivariate analysis, mechanical ventilation duration (OR1.446, 95% CI 1.195-1.749, p<0.001), CPB duration of ≥110 min (OR 1.314, 95% CI 1.072-1.611, p=0.009), erythrocytes transfusion (OR 1.078, 95% CI 1.050-1.106, p<0.001), and postoperative body temperature greater than 38℃ within 3 days (OR 1.234, 95% CI 1.018-1.496, p=0.032) were independent risk factors for CSA-AKI, while ulinastatin use was associated with a reduced incidence of CSA-AKI (OR 0.694, 95% CI 0.557-0.881, p=0.006). CSA-AKI was significantly associated with in-hospital mortality (adjusted HR: 2.218, 95% CI 1.161-4.238, p=0.016), especially in patients needing renal replacement therapy (adjusted HR: 18.683, 95% CI 8.579-40.684, p<0.001). Conclusion Mechanical ventilation duration, erythrocytes transfusion, and postoperative body temperature above 38℃ within 3 days were considered independent risk factors for CSA-AKI. The use of ulinastatin was associated with a reduced incidence of CSA-AKI.

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Section: Discussionmentioning

confidence: 99%

Reassessment of Acute Kidney Injury after Cardiac Surgery: A Retrospective Study

Xie

Wan

et al. 2017

Intern. Med.

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“…Whether this translates to downstream immune dysfunction is unclear. Later, et al showed that in patients undergoing cardiac surgery, patients receiving TXA and EACA showed less upregulation of pro-inflammatory genes and more upregulation of anti-inflammatory genes relative to patients not receiving these medications (95); however, they found no effects on cytokine or growth factor concentrations (96). Lewis and colleagues examined this issue retrospectively in military trauma patients; their results demonstrated no increased risk for infection, and further showed no decrease in time to infection in patients receiving TXA relative to those who had not, suggesting that early immune suppression in TXA-treated patients is not present (97).…”

Section: Conmentioning

confidence: 99%

Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?

Moore

Winfield

Aibiki

et al. 2017

Shock

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Coagulopathy is a common and vexing clinical problem in critically ill patients. Recently, major advances focused on the treatment of coagulopathy in trauma and sepsis have emerged. However, the targeting of coagulopathy with blood product transfusion and drugs directed at attenuating the physiologic response to these conditions have major potential risk to the patient. Therefore, the identification of coagulopathy as a clinical target is an area of uncertainty and controversy. In order to analyze the state of the science regarding coagulopathy in critical illness, a symposium addressing the problem was organized at the 39th annual meeting of the Shock Society in the summer of 2016. This manuscript synthesizes the viewpoints of the four expert panelists at the debate and presents an overview of the potential positive and negative consequences of targeting coagulopathy in trauma and sepsis.

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“…Plasmin‐mediated alteration in the immune response post TBI is an important consideration in the pharmacological treatment of TBI patients. As our findings in plg −/− mice suggested profound immune‐modulatory properties of plasmin and previous studies suggesting immune‐modulatory effects of TXA we then determined whether pharmacological inhibition of plasmin generation would produce similar effects on the immune response after TBI.…”

Section: Discussionmentioning

confidence: 87%

Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

Draxler

Daglas

Fernando

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Traumatic brain injury (TBI) is known to promote immunosuppression, making patients more susceptible to infection, yet potentially exerting protective effects by inhibiting central nervous system (CNS) reactivity. Plasmin, the effector protease of the fibrinolytic system, is now recognized for its involvement in modulating immune function. Objective To evaluate the effects of plasmin and tranexamic acid (TXA) on the immune response in wild‐type and plasminogen‐deficient (plg−/−) mice subjected to TBI. Methods Leukocyte subsets in lymph nodes and the brain in mice post TBI were evaluated by flow cytometry and in blood with a hemocytometer. Immune responsiveness to CNS antigens was determined by Enzyme‐linked Immunosorbent Spot (ELISpot) assay. Fibrinolysis was determined by thromboelastography and measuring D‐dimer and plasmin‐antiplasmin complex levels. Results Plg−/− mice, but not plg+/+ mice displayed increases in both the number and activation of various antigen‐presenting cells and T cells in the cLN 1 week post TBI. Wild‐type mice treated with TXA also displayed increased cellularity of the cLN 1 week post TBI together with increases in innate and adaptive immune cells. These changes occurred despite the absence of systemic hyperfibrinolysis or coagulopathy in this model of TBI. Importantly, neither plg deficiency nor TXA treatment enhanced the autoreactivity within the CNS. Conclusion In the absence of systemic hyperfibrinolysis, plasmin deficiency or blockade with TXA increases migration and proliferation of conventional dendritic cells (cDCs) and various antigen‐presenting cells and T cells in the draining cervical lymph node (cLN) post TBI. Tranexamic acid might also be clinically beneficial in modulating the inflammatory and immune response after TBI, but without promoting CNS autoreactivity.

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Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery

Cited by 44 publications

References 27 publications

Reassessment of Acute Kidney Injury after Cardiac Surgery: A Retrospective Study

Reassessment of Acute Kidney Injury after Cardiac Surgery: A Retrospective Study

Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?

Tranexamic acid modulates the cellular immune profile after traumatic brain injury in mice without hyperfibrinolysis

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