A comparative study of the immune modulating properties of antifibrinolytics in cardiac surgery

Later, Alexander F.L.; Bruggemans, Eline F.; Romijn, Fred P.H.T.M.; Pelt, Johannes van; Klautz, Robert J.M.

doi:10.1016/j.cyto.2012.10.033

Cited by 10 publications

(13 citation statements)

References 28 publications

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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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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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“…Later et al studied cardiac surgery patients treated with TXA, aprotinin, or placebo and assessed plasma levels of 12 pro-and anti-inflammatory cytokines and growth factors 6, 12, 24, and 48 hours after start of cardiopulmonary bypass (CPB). 93 Aprotinin significantly reduced levels of TNF-α and MCP-1 compared with placebo, whereas TXA did not show any effect on inflammatory cytokine expression. However, both aprotinin and to a lesser extent TXA suppressed the upregulation of proinflammatory gene expression and enhanced anti-inflammatory gene expression in cardiac surgery patients.…”

Section: Antifibrinolytics To Reduce the Inflammatory Response To Majmentioning

confidence: 87%

“…Later et al (2013) 93,94 Jiménez et al (2011) 96 Jimenez et al (2007) 95 Graham et al (2012) 97 Greilich et al (2003) 98 Türköz et al (2001) 99 Dorman et al (2008) 100 Hill et al (1995) 101 Greilich et al (2001) 102 Brown et al (2009) 104 Abbreviations: CNS, central nervous system; DCs, dendritic cells; EACA, epsilon aminocaproic acid; EAE, experimental autoimmune encephalomyelitis; TXA, tranexamic acid; u-PA, urokinase-type plasminogen activator; uPAR, urokinase plasminogen activator receptor.…”

Section: Antifibrinolytics In Major Surgerymentioning

confidence: 98%

Plasmin: A Modulator of Immune Function

Draxler

Sashindranath

Medcalf

2016

Semin Thromb Hemost

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Plasmin is the effector protease of the fibrinolytic system, well known for its involvement in fibrin degradation and clot removal. However, plasmin is also recognized as a potent modulator of immunological processes by directly interacting with various cell types including leukocytes (monocytes, macrophages, and dendritic cells) and cells of the vasculature (endothelial cells, smooth muscle cells) as well as soluble factors of the immune system and components of the extracellular matrix. In fact, the removal of misfolded proteins and maintenance of tissue homeostasis seem to be major physiological functions of plasmin. However, a large body of evidence also suggests that excessive plasmin generation frequently contributes to the pathophysiology of acute and chronic inflammatory processes. Hence, one question arising from the broadening effects of plasmin in physiology is whether antifibrinolytic drugs (i.e., tranexamic acid, epsilon aminocaproic acid, or aprotinin) that target plasmin either directly or indirectly and which are commonly used to prevent or treat bleeding might have unintended consequences on the immune response or on other nonfibrinolytic processes in vivo.

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“…In a study conducted by Hsia et al with the aim of exploring the effects of aprotinin or tranexamic acid on proteolytic and cytokine profiles in infants after cardiac surgery, the expression of proinflammatory cytokines and associated matrix metaloproteinases was reduced in an aprotinin group compared with a tranexamic acid group [ 44 ]. Two currently published reports also demonstrated that aprotinin attenuates postoperative expression of pro-inflammatory factors and inflammatory gene expression whereas tranexamic acid does not [ 45 , 46 ]. Theses results were consistent with prior studies of cardiac surgery patients [ 13 , 14 , 47 – 49 ].Because of the retrospective form of the present study, we lacked data for specific biomarkers of inflammation.…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Antifibrinolytic Therapy in Neonatal Cardiac Surgery

et al. 2015

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BackgroundNeonates undergoing open-heart surgery are particularly at risk of postoperative bleeding requiring blood transfusion. Aprotinin has attained high efficacy in reducing the requirement for a blood transfusion following a cardiopulmonary bypass, but is seldom studied in the neonatal age group. The aim of this study was to compare the efficacy and adverse effects of aprotinin and tranexamic acid in neonates undergoing open-heart surgery at a single centre.MethodsBetween October 2003 and March 2008, perioperative data of 552 consecutive neonatal patients undergoing open-heart surgery in Children’s Hospital Boston were reviewed. Among them, 177 did not receive antifibrinolytic therapy (Group A); 100 were treated with tranexamic acid only (Group B); and 275 patients received aprotinin with or without tranexamic acid (Group C). Except for antifibrinolytic therapy, the anaesthesiological and surgical protocols remained identical. Postoperative complications and in-hospital mortality were the primary study endpoints.ResultsBody weight and Risk Adjustment for Congenital Heart Surgery (RACHS-1) scores were statistically comparable among the three groups. No statistically significant differences were observed between the duration of hospitalization, chest tube drainage, reexploration for bleeding, and kidney function impairment. In Group C, less blood was transfused within 24 hours than in GroupB. Operative mortality was similar among the three groups.ConclusionNo further risk and kidney injury were observed in the use of aprotinin in neonatal cardiac surgery, aprotinin demonstrated a reduced requirement for blood transfusion compared with tranexamic acid. Our data provide reasonable evidence that aprotinin and tranexamic acid are safe and efficacious as antifibrinolytic modalities in neonatal patients undergoing cardiac surgery.

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A comparative study of the immune modulating properties of antifibrinolytics in cardiac surgery

Cited by 10 publications

References 28 publications

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

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

Plasmin: A Modulator of Immune Function

The Safety and Efficacy of Antifibrinolytic Therapy in Neonatal Cardiac Surgery

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