Thrombin Generation and Antithrombin Activity in Infants Undergoing Cardiopulmonary Bypass—An Exploratory Study

Elena Ashikhmina, Pamela M. Johnson, Devon O. Aganga, Gregory A. Nuttall, Brian D. Lahr, Hartzell V. Schaff, Joseph A. Dearani

Research output: Contribution to journalArticle

Abstract

Objectives: Coagulopathic bleeding is a major complication of pediatric cardiac surgery. Investigating perioperative dynamics of thrombin generation and antithrombin (AT) activity might provide more insight into the underlying mechanisms of coagulopathy. This can help develop a targeted hemostatic approach in the future. The authors hypothesized that there is a decline in both thrombin generation and AT activity in infants undergoing cardiopulmonary bypass (CPB). Design: Prospective observational study. Setting: Single academic medical center. Participants: Infants <10 kg of weight undergoing cardiac surgery with CPB. Interventions: Blood specimen collection and testing. Measurements and Results: The authors performed assays of thrombin generation and AT activity on the samples of platelet-poor plasma of 25 infants, repeating them at 3 points: before CPB and heparinization, after separation from CPB and protamine administration, and after chest closure. The authors observed a statistically significant decline in thrombin generation shortly after separation from CPB compared with baseline. The geometric mean for lag time was prolonged (4.0 v 5.5 minutes, p = 0.013), and peak thrombin and the net amount of generated thrombin declined almost 3-fold (80.7 v 25.1 nmol, p < 0.001; 1264 v 476 nmol, p < 0.001, respectively). This was accompanied by a decline in AT activity (59.8 v 50.1, p = 0.001). After platelet and cryoprecipitate transfusion, at the case conclusion AT activity had recovered marginally (59.8 v 55.4, p = 0.042), but thrombin generation remained reduced. Conclusions: In pediatric patients <10 kg undergoing cardiac surgery with CPB, thrombin generation and AT activity decline and do not recover completely after transfusion of platelets and cryoprecipitate.

Original languageEnglish (US)
JournalJournal of Cardiothoracic and Vascular Anesthesia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Antithrombins
Thrombin
Cardiopulmonary Bypass
Thoracic Surgery
Platelet Transfusion
Blood Specimen Collection
Pediatrics
Protamines
Hemostatics
Observational Studies
Thorax
Blood Platelets
Prospective Studies
Hemorrhage
Weights and Measures

Keywords

  • antithrombin
  • cardiopulmonary bypass
  • coagulopathy
  • congenital heart disease
  • thrombin generation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

Cite this

Thrombin Generation and Antithrombin Activity in Infants Undergoing Cardiopulmonary Bypass—An Exploratory Study. / Ashikhmina, Elena; Johnson, Pamela M.; Aganga, Devon O.; Nuttall, Gregory A.; Lahr, Brian D.; Schaff, Hartzell V.; Dearani, Joseph A.

In: Journal of Cardiothoracic and Vascular Anesthesia, 01.01.2019.

Research output: Contribution to journalArticle

Ashikhmina, Elena ; Johnson, Pamela M. ; Aganga, Devon O. ; Nuttall, Gregory A. ; Lahr, Brian D. ; Schaff, Hartzell V. ; Dearani, Joseph A. / Thrombin Generation and Antithrombin Activity in Infants Undergoing Cardiopulmonary Bypass—An Exploratory Study. In: Journal of Cardiothoracic and Vascular Anesthesia. 2019.
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AU - Ashikhmina, Elena

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AU - Aganga, Devon O.

AU - Nuttall, Gregory A.

AU - Lahr, Brian D.

AU - Schaff, Hartzell V.

AU - Dearani, Joseph A.

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AB - Objectives: Coagulopathic bleeding is a major complication of pediatric cardiac surgery. Investigating perioperative dynamics of thrombin generation and antithrombin (AT) activity might provide more insight into the underlying mechanisms of coagulopathy. This can help develop a targeted hemostatic approach in the future. The authors hypothesized that there is a decline in both thrombin generation and AT activity in infants undergoing cardiopulmonary bypass (CPB). Design: Prospective observational study. Setting: Single academic medical center. Participants: Infants <10 kg of weight undergoing cardiac surgery with CPB. Interventions: Blood specimen collection and testing. Measurements and Results: The authors performed assays of thrombin generation and AT activity on the samples of platelet-poor plasma of 25 infants, repeating them at 3 points: before CPB and heparinization, after separation from CPB and protamine administration, and after chest closure. The authors observed a statistically significant decline in thrombin generation shortly after separation from CPB compared with baseline. The geometric mean for lag time was prolonged (4.0 v 5.5 minutes, p = 0.013), and peak thrombin and the net amount of generated thrombin declined almost 3-fold (80.7 v 25.1 nmol, p < 0.001; 1264 v 476 nmol, p < 0.001, respectively). This was accompanied by a decline in AT activity (59.8 v 50.1, p = 0.001). After platelet and cryoprecipitate transfusion, at the case conclusion AT activity had recovered marginally (59.8 v 55.4, p = 0.042), but thrombin generation remained reduced. Conclusions: In pediatric patients <10 kg undergoing cardiac surgery with CPB, thrombin generation and AT activity decline and do not recover completely after transfusion of platelets and cryoprecipitate.

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