Update on Antithrombin for the Treatment of Burn Trauma and Smoke Inhalation Injury

Rehberg, Sebastian; Traber, Daniel L.; Enkhbaatar, Perenlei

doi:10.1007/978-1-4419-5562-3_27

Cited by 3 publications

(2 citation statements)

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“…In this context, it is important to consider that rhAT provides both anticoagulant-dependent, that is, mediated by a lower activity of coagulant factors such as thrombin, and anticoagulantindependent anti-inflammatory effects mediated by interaction with the syndecans 4 receptor, for example. 4 The anticoagulantindependent anti-inflammatory effects, such as the inhibition of neutrophil activation, were blocked by heparin, as suggested by the higher number of neutrophils in the pulmonary lymph and higher histologic scores for polymorphonuclear cells in the lungs of the triple therapy group as compared with the AT i.v. group.…”

Section: Discussionmentioning

confidence: 98%

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome

Rehberg

Yamamoto

Sousse

et al. 2014

Journal of Trauma and Acute Care Surgery

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Section: Discussionmentioning

confidence: 98%

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome

Rehberg

Yamamoto

Sousse

et al. 2014

Journal of Trauma and Acute Care Surgery

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“…This finding is supported by numerous experimental studies, using even higher doses than 6 IU/kg/hr (29, 31). In respect to bleeding complications, the combination with heparin rather than the dose of antithrombin seems to be the critical factor (37). Notably, the prevention of a severe decrease in ATIII plasma levels might represent itself a beneficial effect because mortality of burn patients is associated with the reduction of ATIII plasma levels (5).…”

Section: Discussionmentioning

confidence: 99%

Antithrombin Attenuates Vascular Leakage via Inhibiting Neutrophil Activation in Acute Lung Injury

Rehberg

Yamamoto

Sousse

et al. 2013

Critical Care Medicine

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Objective To test the hypothesis that restoration of antithrombin plasma concentrations attenuates vascular leakage by inhibiting neutrophil activation through syndecan-4 receptor inhibition in an established ovine model of acute lung injury. Design Randomized controlled laboratory experiment. Setting University animal research facility. Subjects Eighteen chronically instrumented sheep. Interventions Following combined burn and smoke inhalation injury (40% of total body surface area, third-degree flame burn; 4 × 12 breaths of cold cotton smoke), chronically instrumented sheep were randomly assigned to receive an IV infusion of 6 IU/kg/hr recombinant human antithrombin III or normal saline (n = 6 each) during the 48-hour study period. In addition, six sham animals (not injured, continuous infusion of vehicle) were used to obtain reference values for histological and immunohistochemical analyses. Measurements and Main Results Compared to control animals, recombinant human antithrombin III reduced the number of neutrophils per hour in the pulmonary lymph (p < 0.01 at 24 and 48 hr), alveolar neutrophil infiltration (p = 0.04), and pulmonary myeloperoxidase activity (p = 0.026). Flow cytometric analysis revealed a significant reduction of syndecan-4-positive neutrophils (p = 0.002 vs control at 24 hr). Treatment with recombinant human antithrombin III resulted in a reduction of pulmonary nitrosative stress (p = 0.002), airway obstruction (bronchi: p = 0.001, bronchioli: p = 0.013), parenchymal edema (p = 0.044), and lung bloodless wet-to-dry-weight ratio (p = 0.015). Clinically, recombinant human antithrombin III attenuated the increased pulmonary transvascular fluid flux (12–48 hr: p ≤ 0.001 vs control each) and the deteriorated pulmonary gas exchange (12–48 hr: p < 0.05 vs control each) without increasing the risk of bleeding. Conclusions The present study provides evidence for the interaction between antithrombin and neutrophils in vivo, its pathophysiological role in vascular leakage, and the therapeutic potential of recombinant human antithrombin III in a large animal model of acute lung injury.

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Antithrombin in the treatment of burn trauma

Kowal-Vern

Orkin

2016

WJCCM

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Antithrombin (AT) is a natural anticoagulant with antiinflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma.

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Update on Antithrombin for the Treatment of Burn Trauma and Smoke Inhalation Injury

Cited by 3 publications

References 44 publications

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome

Advantages and pitfalls of combining intravenous antithrombin with nebulized heparin and tissue plasminogen activator in acute respiratory distress syndrome

Antithrombin Attenuates Vascular Leakage via Inhibiting Neutrophil Activation in Acute Lung Injury

Antithrombin in the treatment of burn trauma

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