Myocardial injury after non-cardiac surgery and per operative fibrin metabolism in patients undergoing hip-fracture surgery: an observational study

Abstract

Myocardial injury after non-cardiac surgery (MINS) is associated with a 2-3-fold increased risk of subsequent major cardiovascular events and postoperative mortality. The pathological mechanism behind MINS is not fully uncovered. We hypothesized that patients with MINS following hip fracture surgery would have an altered haemostatic balance pre- and postoperative compared with patients without MINS. This was investigated in a prospective single-centre observational study including patients consecutively. The outcomes were changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements in patients developing MINS and patients who did not. Outcomes were measured preoperatively and two hours postoperatively. Seventy-two patients were included whereof 26 (36%) patients developed MINS. D-dimer delta values were significantly higher in patients developing MINS than in patients who did not (p = 0.01). After adjusting for age, sex, smoking, alcohol abuse, atrial fibrillation, anticoagulant medication preoperative CRP, preoperative creatinine and duration of surgery, the association remained significant (p = 0.04). There were no significant changes in thrombin generation, in markers of fibrinogen/fibrin turnover besides D-dimer, or in fibrin structure measurements pre- and postoperatively between patients with and without MINS. As such, a relationship between the coagulative and fibrinolytic activity and MINS cannot be ruled out in patients with MINS after hip fracture surgery. Registration: The study was an observational sub-study to a multicentre randomised clinical trial registered at ClinicalTrials.gov (NCT02344797)

Keywords:

• Surgery
• myocardial ischemia
• orthopedic surgery
• fibrin
• blood coagulation

Acknowledgements

The authors would like to acknowledge the work of Johannes Jakobsen Sidelmann overseeing the laboratory analyses and assisting in interpretation of the data.

Ethics statement and patient consent

This prospective observational study was a sub-study of a multicentre, randomised clinical trial (PIXIE trial) [14]. The trial was approved by the Regional Ethics Committee of Region Zealand Denmark (no. SJ-428), and by the Danish Data Protection Agency (no. Reg-115-2014). The trial was registered on ClinicalTrials.gov (no. NCT02344797). Changes were made to the analysis plan after patient inclusion. In the trial registration, analysis for coagulation blood markers were planned two hours after surgery, at postoperative day one and two. Economic prioritising resulted in analyses of coagulation markers two hours after surgery solely. Patients were not included in the study if a written informed consent to participate could not be obtained.

Author contributions

SE, IG and AMM contributed to the design of the original trial to which this study is a sub-study. SE and AMM contributed to the acquisition of data and the interpretation of data, the latter in collaboration with KW. KW drafted the first manuscript, and all authors critically revised it. All authors approved the final version of the manuscript and the corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

The datasets analysed during the current study are available in an anonymised form from the corresponding author on reasonable request.

Additional information

Funding

The following institutions and fonds supported the execution of this study: The University of Copenhagen, Axel Muusfeldts Fond, Snedkermester Sophus Jacobsen og Hustru Anna Jacobsens Fond, Oda og Hans Svenningsens Fond, Frimodt-Heineke Fonden, Toyota Foundation and Beckett-Fonden. They had no influence on the design of the study, the data collection, data analysis, or the interpretation of data. Nor did they influence the writing of the manuscript.