Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Effects of Antithrombin Versus Placebo on the Coagulation System in Infants with Low Antithrombin Undergoing Congenital Cardiac Surgery

Edmund H. Jooste, Rebecca Scholl, Yi Hung Wu, Robert D.B. Jaquiss, Andrew J. Lodge, Warwick A. Ames, H. Mayumi Homi, Kelly A. Machovec, Nathaniel H. Greene, Brian S. Donahue, Nirmish Shah, Claudia Benkwitz

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. Design: Randomized, double-blinded, placebo-controlled prospective study. Setting: Multicenter study performed in 2 academic hospitals. Participants: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. Interventions: Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. Measurements and Main Results: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. Conclusion: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.

Original languageEnglish (US)
JournalJournal of Cardiothoracic and Vascular Anesthesia
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Antithrombins
Thoracic Surgery
Randomized Controlled Trials
Placebos
Heparin
Postoperative Period
Hemorrhage
Chest Tubes
Multicenter Studies
Demography
Prospective Studies

Keywords

  • antithrombin
  • cardiopulmonary bypass
  • congenital heart disease
  • heparin
  • pediatric anticoagulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

Cite this

Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Effects of Antithrombin Versus Placebo on the Coagulation System in Infants with Low Antithrombin Undergoing Congenital Cardiac Surgery. / Jooste, Edmund H.; Scholl, Rebecca; Wu, Yi Hung; Jaquiss, Robert D.B.; Lodge, Andrew J.; Ames, Warwick A.; Homi, H. Mayumi; Machovec, Kelly A.; Greene, Nathaniel H.; Donahue, Brian S.; Shah, Nirmish; Benkwitz, Claudia.

In: Journal of Cardiothoracic and Vascular Anesthesia, 01.01.2018.

Research output: Contribution to journalArticle

Jooste, Edmund H. ; Scholl, Rebecca ; Wu, Yi Hung ; Jaquiss, Robert D.B. ; Lodge, Andrew J. ; Ames, Warwick A. ; Homi, H. Mayumi ; Machovec, Kelly A. ; Greene, Nathaniel H. ; Donahue, Brian S. ; Shah, Nirmish ; Benkwitz, Claudia. / Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Effects of Antithrombin Versus Placebo on the Coagulation System in Infants with Low Antithrombin Undergoing Congenital Cardiac Surgery. In: Journal of Cardiothoracic and Vascular Anesthesia. 2018.
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abstract = "Objectives: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100{\%} improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. Design: Randomized, double-blinded, placebo-controlled prospective study. Setting: Multicenter study performed in 2 academic hospitals. Participants: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70{\%} undergoing CPB surgery. Interventions: Antithrombin levels were increased with exogenous antithrombin to 100{\%} functional level intraoperatively before surgical incision. Measurements and Main Results: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels ({\%}) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. Conclusion: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.",
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author = "Jooste, {Edmund H.} and Rebecca Scholl and Wu, {Yi Hung} and Jaquiss, {Robert D.B.} and Lodge, {Andrew J.} and Ames, {Warwick A.} and Homi, {H. Mayumi} and Machovec, {Kelly A.} and Greene, {Nathaniel H.} and Donahue, {Brian S.} and Nirmish Shah and Claudia Benkwitz",
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T1 - Double-Blind, Randomized, Placebo-Controlled Trial Comparing the Effects of Antithrombin Versus Placebo on the Coagulation System in Infants with Low Antithrombin Undergoing Congenital Cardiac Surgery

AU - Jooste, Edmund H.

AU - Scholl, Rebecca

AU - Wu, Yi Hung

AU - Jaquiss, Robert D.B.

AU - Lodge, Andrew J.

AU - Ames, Warwick A.

AU - Homi, H. Mayumi

AU - Machovec, Kelly A.

AU - Greene, Nathaniel H.

AU - Donahue, Brian S.

AU - Shah, Nirmish

AU - Benkwitz, Claudia

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objectives: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. Design: Randomized, double-blinded, placebo-controlled prospective study. Setting: Multicenter study performed in 2 academic hospitals. Participants: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. Interventions: Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. Measurements and Main Results: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. Conclusion: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.

AB - Objectives: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. Design: Randomized, double-blinded, placebo-controlled prospective study. Setting: Multicenter study performed in 2 academic hospitals. Participants: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. Interventions: Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. Measurements and Main Results: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. Conclusion: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.

KW - antithrombin

KW - cardiopulmonary bypass

KW - congenital heart disease

KW - heparin

KW - pediatric anticoagulation

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DO - 10.1053/j.jvca.2018.05.052

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JO - Journal of Cardiothoracic and Vascular Anesthesia

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SN - 1053-0770

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