The Influence of Antithrombin Substitution on Heparin Sensitivity and Activation of Hemostasis During Coronary Artery Bypass Graft Surgery

Dietrich, Wulf; Busley, Raimund; Spannagi, Michael; Braun, Siegmund; Schuster, Tibor; Lison, Susanne

doi:10.1097/01.sa.0000443067.64428.2e

Cited by 8 publications

(18 citation statements)

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“…However, they found that AT activity is not associated with impaired response to heparin when using target ACTs of 300 to 350 s. Despite this finding, multiple case reports (74,75), a retrospective study (76), and prospective clinical trials (77)(78)(79) have reported that AT treatment (range, 500-3,400 IU) for heparin resistance during CPB increased ACT to values acceptable for CPB. In a dose-finding study to identify an AT dosage that would result in > 100 % AT activity at the end of cardiac surgery, Dietrich et al found that the dosage needed to be quite high (approximately 50 IU/kg) to restore normal physiologic AT values (80).…”

Section: Cardiac Surgery With Cardiopulmonary Bypassmentioning

confidence: 99%

Antithrombin: anti-inflammatory properties and clinical applications

Levy¹,

Sniecinski²,

Welsby³

et al. 2016

Thromb Haemost

142

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SummaryMany humoral and cellular components participate in bidirectional communication between the coagulation and inflammation pathways. Natural anticoagulant proteins, including antithrombin (AT), tissue factor pathway inhibitor, and protein C, suppress proinflammatory mediators. Conversely, inflammation blunts anticoagulant activity and, when uncontrolled, promotes systemic inflammation-induced coagulation, such as those that occur in disseminated intravascular coagulation and severe sepsis. This review discusses the mechanisms of action and clinical use of AT concentrate in critically ill patients and in the settings of perioperative anticoagulation management for surgery and obstetrics. AT is a serine protease inhibitor with broad anticoagulant activity and potent anti-inflammatory properties. In clinical conditions associated with hereditary or acquired AT deficiency, administration of AT concentrate has been shown to restore proper haemostasis and attenuate inflammation. Of note, AT modulates inflammatory responses not only by inhibiting thrombin and other clotting factors that induce cytokine activity and leukocyteendothelial cell interaction, but also by coagulation-independent effects, including direct interaction with cellular mediators of inflammation. An increasing body of evidence suggests that AT concentrate may be a potential therapeutic agent in certain clinical settings associated with inflammation. In addition to the well-known anticoagulation properties of AT for the treatment of hereditary AT deficiency, AT also possesses noteworthy anti-inflammatory properties that could be valuable in treating acquired AT deficiency, which often result in thrombotic states associated with an inflammatory component.

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Section: Cardiac Surgery With Cardiopulmonary Bypassmentioning

confidence: 99%

Antithrombin: anti-inflammatory properties and clinical applications

Levy¹,

Sniecinski²,

Welsby³

et al. 2016

Thromb Haemost

142

View full text Add to dashboard Cite

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“…In vitro and in vivo studies of adult patients during CPB indicate that low antithrombin levels correlate with a decreased responsiveness to heparin and result in an activation/consumption of coagulation factors (10). Antithrombin supplementation to adults undergoing surgery requiring CPB has resulted in improved laboratory response to heparin (11)(12)(13)(14), decrease in hemostatic activation (13,15), and no significant adverse outcomes (12,14,16).…”

Section: Introductionmentioning

confidence: 99%

“…Antithrombin levels are decreased in normal neonates compared with older children and adults (6) and are even lower in infants with congenital heart disease (7)(8)(9). Antithrombin supplementation to adults undergoing surgery requiring CPB has resulted in improved laboratory response to heparin (11)(12)(13)(14), decrease in hemostatic activation (13,15), and no significant adverse outcomes (12,14,16). Antithrombin supplementation to adults undergoing surgery requiring CPB has resulted in improved laboratory response to heparin (11)(12)(13)(14), decrease in hemostatic activation (13,15), and no significant adverse outcomes (12,14,16).…”

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confidence: 99%

A Pilot Study of Antithrombin Replacement Prior to Cardiopulmonary Bypass in Neonates

et al. 2015

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Neonates have low levels of antithrombin. Inadequate anticoagulation during cardiopulmonary bypass (CPB) due to low antithrombin activity may result in a poor preservation of the coagulation system during bypass. We hypothesize that antithrombin replacement to neonates prior to CPB will preserve the hemostatic system and result in less postoperative bleeding. A randomized, double-blinded, placebo-controlled pilot study of antithrombin replacement to neonates prior to CPB was conducted. Preoperative antithrombin levels determined the dose of recombinant antithrombin or placebo to be given. Antithrombin levels were measured following the dosing of the antithrombin/placebo, after initiation of bypass, near the completion of bypass, and upon intensive care unit admission. Eight subjects were enrolled. No subject had safety concerns. Mediastinal exploration occurred in two antithrombin subjects and one placebo subject. Antithrombin activity levels were significantly higher in the treated group following drug administration; levels continued to be higher than preoperatively but not different from the placebo group at all other time points. Total heparin administration was less in the antithrombin group; measurements of blood loss were similar in both groups. A single dose of recombinant antithrombin did not maintain 100% activity levels throughout the entire operation. Although no safety concerns were identified in this pilot study, a larger trial is necessary to determine clinical efficacy.

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“…Antithrombin supplementation has been discussed for a long time in adults and children undergoing cardiac surgery, [2][3][4][5] but the studies published to date failed to demonstrate the beneficial effect of AT supplementation on thrombin generation, bleeding, and the incidence of thrombotic complications. Antithrombin supplementation is thought to improve heparin sensitivity and anticoagulation, decrease (or abolish) thrombin generation, decrease consumption coagulopathy, and decrease the incidence of excessive bleeding and thrombotic complications.…”

mentioning

confidence: 99%

“…In another study, Dietrich et al compared the effect of increasing AT doses necessary to achieve >100% AT activity at the end of cardiac surgery and the influence of AT on heparin sensitivity. 5 The authors reported that high dosages (eg, 50 U/kg) of AT were required to preserve physiologic AT activity during coronary artery bypass graft surgery and to significantly enhance heparin sensitivity. However, despite AT substitution, a significant decrease in AT activity accompanied by high levels of thrombin generation was observed up to 5 days postoperatively, indicating increased prothrombotic activity.…”

mentioning

confidence: 99%