Observational Study

. 2022 Mar;69(3):311-322.

doi: 10.1007/s12630-021-02165-1. Epub 2021 Dec 22.

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Justyna Bartoszko^{1

2

3}, Han Li⁴, John Fitzgerald⁵, Loretta T S Ho⁶, Cyril Serrick⁴, Walter H A Kahr^{7

8}, Peter L Gross⁹, Keyvan Karkouti^{10

6

11

12

13}

Affiliations

¹ Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada. justyna.bartoszko@uhn.ca.
² Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. justyna.bartoszko@uhn.ca.
³ Department of Anesthesia and Pain Management, University Health Network, Toronto General Hospital, 200 Elizabeth Street, 3EN-464, Toronto, ON, M5G 2C4, Canada. justyna.bartoszko@uhn.ca.
⁴ Perfusion Services, University Health Network, Toronto, ON, Canada.
⁵ Department of Anaesthesia and Intensive Care, Beaumont Hospital, Dublin, Ireland.
⁶ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Departments of Paediatrics and Biochemistry, University of Toronto, Toronto, ON, Canada.
⁸ Division of Haematology/Oncology, Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁹ Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada.
¹¹ Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
¹² Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹³ Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.

PMID: 34939141
DOI: 10.1007/s12630-021-02165-1

Observational Study

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Justyna Bartoszko et al. Can J Anaesth. 2022 Mar.

. 2022 Mar;69(3):311-322.

doi: 10.1007/s12630-021-02165-1. Epub 2021 Dec 22.

Authors

Justyna Bartoszko^{1

2

3}, Han Li⁴, John Fitzgerald⁵, Loretta T S Ho⁶, Cyril Serrick⁴, Walter H A Kahr^{7

8}, Peter L Gross⁹, Keyvan Karkouti^{10

6

11

12

13}

Affiliations

¹ Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada. justyna.bartoszko@uhn.ca.
² Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. justyna.bartoszko@uhn.ca.
³ Department of Anesthesia and Pain Management, University Health Network, Toronto General Hospital, 200 Elizabeth Street, 3EN-464, Toronto, ON, M5G 2C4, Canada. justyna.bartoszko@uhn.ca.
⁴ Perfusion Services, University Health Network, Toronto, ON, Canada.
⁵ Department of Anaesthesia and Intensive Care, Beaumont Hospital, Dublin, Ireland.
⁶ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Departments of Paediatrics and Biochemistry, University of Toronto, Toronto, ON, Canada.
⁸ Division of Haematology/Oncology, Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁹ Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada.
¹¹ Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.
¹² Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹³ Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.

PMID: 34939141
DOI: 10.1007/s12630-021-02165-1

Abstract
in English, French

Background: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with coagulopathic bleeding. Impaired thrombin generation may be an important cause of coagulopathic bleeding but is poorly measured by existing hemostatic assays. We examined thrombin generation during cardiac surgery, using calibrated automated thrombography, and its association with bleeding outcomes.

Methods: We conducted a prospective observational study in 100 patients undergoing cardiac surgery with CPB. Calibrated automated thrombography parameters were expressed as a ratio of post-CPB values divided by pre-CPB values. The association of thrombin generation parameters for bleeding outcomes was compared with conventional tests of hemostasis, and the outcomes of patients with the most severe post-CPB impairment in thrombin generation (≥ 80% drop from baseline) were compared with the rest of the cohort.

Results: All 100 patients were included in the final analysis, with a mean age of 63 (12) yr, 31 (31%) female, and 94 (94%) undergoing bypass and/or valve surgery. Post-CPB, peak thrombin decreased by a median of 73% (interquartile range [IQR], 49-91%) (P < 0.001) and total thrombin generation, expressed as the endogenous thrombin potential (ETP), decreased 56% [IQR, 30-83%] (P < 0.001). In patients with ≥ 80% decrease in ETP, 21% required re-exploration for bleeding compared with 7% in the rest of the cohort (P = 0.04), and 48% required medical or surgical treatment for hemostasis compared with 27% in the rest of the cohort (P = 0.04).

Conclusions: Thrombin generation is significantly impaired by CPB and associated with higher bleeding severity. Clinical studies aimed at the identification and treatment of patients with impaired thrombin generation are warranted.

RéSUMé: CONTEXTE: La chirurgie cardiaque avec circulation extracorporelle (CEC) est associée à des saignements sur coagulopathie. L’altération de la génération de thrombine peut constituer une cause importante de saignement sur coagulopathie, mais elle est mal mesurée par les tests d’hémostase existants. Nous avons examiné la génération de thrombine pendant la chirurgie cardiaque à l’aide d’une thrombographie automatisée calibrée ainsi que son association avec les issues hémorragiques. MéTHODE: Nous avons réalisé une étude observationnelle prospective portant sur 100 patients bénéficiant d’une chirurgie cardiaque sous CEC. Les paramètres de thrombographie automatisée calibrée ont été exprimés sous forme du rapport entre les valeurs post-CEC divisées par les valeurs pré-CEC. L’association des paramètres de génération de thrombine pour les issues hémorragiques a été comparée aux tests conventionnels de l’hémostase, et les issues des patients présentant l’altération post-CEC la plus prononcée dans la génération de thrombine (baisse ≥ 80 % par rapport aux valeurs de base) ont été comparées au reste de la cohorte. RéSULTATS: Les 100 patients ont tous été inclus dans l’analyse finale, avec un âge moyen de 63 (12) ans, 31 (31 %) femmes et 94 (94 %) subissant une chirurgie de pontage et / ou une chirurgie valvulaire. Après la CEC, le pic de thrombine a diminué d’une médiane de 73 % (écart interquartile [ÉIQ], 49 à 91 %) (P < 0,001) et la génération de thrombine totale, exprimée en potentiel de thrombine endogène (PTE), a diminué de 56 % [ÉIQ, 30–83 %] (P < 0,001). Chez les patients présentant une diminution ≥ 80 % du PTE, 21 % ont nécessité une nouvelle exploration pour dépister les saignements, comparativement à 7 % dans le reste de la cohorte (P = 0,04), et 48 % ont nécessité un traitement médical ou chirurgical pour l’hémostase, comparativement à 27 % dans le reste de la cohorte (P = 0,04). CONCLUSION: La génération de thrombine est significativement altérée par la CEC et associée à des saignements plus graves. Des études cliniques visant à identifier et à traiter les patients présentant une altération de la génération de thrombine sont recommandées.

Keywords: Blood coagulation disorders; Cardiac surgical procedures; Hemostasis; Perioperative care; Thrombin.

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References

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The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Affiliations

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Authors

Affiliations

Abstract
in English, French

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Abstract in English, French

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Abstract
in English, French