Use of Coagulation Factor Concentrates and Blood Transfusion in Cardiac Surgery: A Retrospective Cohort Study of Adults with Hereditary and Acquired Bleeding Disorders

Academic Background

Cardiac surgery is one of the high-risk procedures, especially for patients with bleeding disorders, as it significantly increases the risk of perioperative bleeding and allogeneic blood transfusions. Bleeding disorders are categorized into hereditary and acquired types. Hereditary bleeding disorders include hemophilia and von Willebrand disease (VWD), while acquired bleeding disorders are often associated with liver diseases, antiphospholipid antibody syndrome, and other conditions. In recent years, the use of coagulation factor concentrates (CFCs) has gradually increased, and these agents may play an important role in reducing bleeding risk, thromboembolic events, and healthcare costs. However, existing research on the use of these agents in cardiac surgery patients and their impact on patient outcomes remains limited.

This study aims to describe the use of coagulation factor concentrates and allogeneic blood products in cardiac surgery patients by analyzing data from the Premier Health Database in the United States, and to assess their correlation with perioperative bleeding, thromboembolic events, hospital costs, and other outcomes.

Source of the Paper

This paper was authored by Kenichi A. Tanaka et al., with contributors from the Department of Anesthesiology at the University of Oklahoma Health Sciences Center, the Department of Pathology at Emory Healthcare, and other institutions. The paper was published online ahead of print on October 18, 2024, in the British Journal of Anaesthesia, Volume 133, Issue 6, pages 1150-1158.

Research Methods

Data Source

The study utilized the Premier Health Database (PHD), a hospital-based, service-level, all-payer discharge database that covers inpatient and outpatient data from both urban and rural areas in the United States. The database includes data from 1,100 hospitals, 372 of which provide cardiac surgery services. All data were anonymized in compliance with the Health Insurance Portability and Accountability Act (HIPAA).

Patient Selection

The study screened adult patients (aged ≥18 years) who underwent cardiac surgeries such as coronary artery bypass grafting (CABG), mitral or aortic valve repair or replacement between 2017 and 2021. These patients were categorized into hereditary bleeding disorder, acquired bleeding disorder, and non-bleeding disorder groups based on the International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes. Hereditary bleeding disorders included hemophilia A (D66), hemophilia B (D67), von Willebrand disease (D68.0), and factor XI deficiency (D68.1). Acquired bleeding disorders included acquired hemophilia (D68.311), antiphospholipid antibody-related bleeding (D68.312), and acquired coagulation factor deficiency (D68.4).

Study Outcomes

The primary outcomes were the use of coagulation factor concentrates and allogeneic blood products. Secondary outcomes included hospital costs, pharmacy costs, blood bank costs, operative duration, perioperative bleeding, thromboembolic events, acute kidney injury (AKI), length of hospital stay, and mortality.

Statistical Analysis

No sample size calculation was performed, as this was an exploratory and descriptive study. Categorical data were summarized using frequencies and proportions, while continuous data were described using means, standard deviations, or medians and interquartile ranges. Group differences were analyzed using chi-square tests, Fisher’s exact tests, t-tests, or Wilcoxon rank-sum tests, with a significance level set at α<0.05.

Results

Patient Characteristics

A total of 1,662 patients with bleeding disorders and 8,202 patients without bleeding disorders were screened from 372 hospitals. Ultimately, the hereditary bleeding disorder group included 449 patients, the acquired bleeding disorder group included 1,162 patients, and the non-bleeding disorder group included 7,261 patients. In the hereditary bleeding disorder group, von Willebrand disease accounted for 27.8%, hemophilia A for 10.5%, hemophilia B for 4.0%, and factor XI deficiency for 4.0%. In the acquired bleeding disorder group, 99.8% of patients were diagnosed with acquired coagulation factor deficiency (D68.4).

Use of Coagulation Factor Concentrates

The use of coagulation factor concentrates was significantly higher in the acquired bleeding disorder group compared to the hereditary bleeding disorder and non-bleeding disorder groups. In the acquired bleeding disorder group, 24% of patients received recombinant activated factor VII (FVIIa), and 11.7% received prothrombin complex concentrate (PCC). In the hereditary bleeding disorder group, 35.3% of patients received von Willebrand factor (VWF), factor VIII (FVIII), or factor IX (FIX) concentrates, and 43.2% received desmopressin (DDAVP).

Complications and Hospital Outcomes

The complication rate was significantly higher in the acquired bleeding disorder group, with a perioperative bleeding rate of 15.8% and a thromboembolic event rate of 19.2%. This group also had significantly longer hospital and intensive care unit (ICU) stays, with the highest mortality rate (19.2%). The hereditary bleeding disorder group had slightly longer hospital and ICU stays compared to the non-bleeding disorder group, but the difference was not significant.

Cost Analysis

The median total hospital cost for the acquired bleeding disorder group was $79,502, significantly higher than that of the hereditary bleeding disorder group ($54,674) and the non-bleeding disorder group ($43,196). The median blood bank cost for the acquired bleeding disorder group was $10,925, 2.4 times higher than that of the hereditary bleeding disorder group and 5.7 times higher than that of the non-bleeding disorder group.

Discussion

Management of Hereditary Bleeding Disorders

Patients with hereditary bleeding disorders are typically managed with preoperative prophylactic factor replacement to maintain plasma factor levels at 80%-100%, followed by gradual postoperative tapering. This study shows that hereditary bleeding disorder patients can safely undergo cardiac surgery with appropriate factor replacement therapy, as their hospital and ICU stays were only slightly longer than those of non-bleeding disorder patients.

Challenges in Acquired Bleeding Disorders

Patients with acquired bleeding disorders often have complex conditions such as liver diseases, which significantly increase the risk of postoperative bleeding and complications. This study found that the acquired bleeding disorder group had longer operative times, more postoperative complications, and significantly higher hospital costs. Despite the use of coagulation factor concentrates, these patients still faced a high risk of thromboembolic events and mortality.

Costs and Resource Utilization

The healthcare costs for the acquired bleeding disorder group were significantly higher than those of the other groups, particularly for blood bank and pharmacy costs. This indicates that the treatment of acquired bleeding disorder patients not only requires more medical resources but may also lead to higher healthcare costs.

Conclusion

This study demonstrates that in cardiac surgery, patients with acquired bleeding disorders require more coagulation factor concentrates and blood products, and they experience significantly higher rates of postoperative complications and healthcare costs. Hereditary bleeding disorder patients can safely undergo surgery with appropriate factor replacement therapy, with only slight increases in hospital stays and costs. Future research should further optimize perioperative hemostasis and thromboprophylaxis strategies to improve patient outcomes and reduce healthcare costs.

Key Findings

1. Important Findings: Patients with acquired bleeding disorders experienced significantly higher rates of bleeding and thromboembolic events after using coagulation factor concentrates, and their healthcare costs were significantly higher than those of hereditary bleeding disorder patients and non-bleeding disorder patients.
2. Methodological Innovation: This study is the first to systematically analyze the use of coagulation factor concentrates in cardiac surgery and their impact on patient outcomes using a large-scale insurance claims database.
3. Clinical Significance: The results highlight the importance of optimizing perioperative hemostasis management and thromboprophylaxis strategies, particularly for patients with acquired bleeding disorders.

Additional Valuable Information

The limitations of this study include the use of insurance claims data, which may contain coding errors or missing data, and the lack of detailed laboratory data and treatment timing information. Nevertheless, this study provides important reference data for the management of bleeding disorder patients in cardiac surgery.