Perioperative blood transfusions are often necessary to stabilize patients undergoing major surgery, especially those with cancer. However, a comprehensive new study, The ARCA-1 Trial, published in Anesthesia & Analgesia (April 2025) by Cata et al., raises concerns about their long-term safety. The study presents strong evidence that perioperative transfusion of packed red blood cells (pRBCs) in cancer surgery is linked with increased 1-year mortality and adverse postoperative outcomes.

Study overview: the ARCA-1 trial

The ARCA-1 (Perioperative Care in the Cancer Patient-1) trial is the largest prospective, international, multicenter observational study to date examining the impact of perioperative blood transfusions on outcomes following major cancer surgery.

Study design

• Type: Prospective observational cohort
• Participants: 1079 patients undergoing elective noncardiac cancer surgery with curative intent
• Time frame: July 2020 – December 2021
• Centers: 16 centers across North America, Asia, and Europe

Objectives

• Primary endpoint: 1-year all-cause mortality
• Secondary endpoints:
  • 30-day morbidity and mortality
  • Cancer-specific 1-year mortality
  • Overall survival (OS)
  • Postoperative complications

Major findings

Transfusion rates and triggers

• 21.1% of patients received perioperative pRBC transfusions.
• Transfusions typically occurred when hemoglobin (Hb) fell between 7 and 9 g/dL.
• Only 9% of transfusions were due to overt organ hypoperfusion, indicating a potentially liberal use of transfusions.
  

Mortality impact

• 1-year mortality was 19.7% in transfused patients vs 6.5% in non-transfused.
• Dose-response relationship observed:
  • 0 units: 7.2% mortality
  • 1–2 units: 18.2%
  • 2 units: 31%

Cancer progression and survival

• Cancer progression within 1 year:
  • Transfused: 32.6%
  • Nontransfused: 18.9%
• Cancer-specific 1-year mortality:
  • Transfused: 13.6%
  • Nontransfused: 4.6%
• Overall survival:
  • Transfused patients had an 85% higher hazard of death
    

Why might transfusions worsen outcomes?

Several mechanisms may explain this association:

• Transfusion-related immunomodulation (TRIM):
  • pRBCs contain > 3000 proteins that suppress immune functions.
  • Inhibition of cytotoxic T cells and monocytes.
  • Increased levels of prostaglandins, growth factors, and angiogenic cytokines.
    
• Promotion of cancer microenvironment:
  • Enhances conditions favorable to tumor recurrence and metastasis.
    
• Storage-related damage:
  • Longer storage times increase oxidative stress and decrease red cell efficacy.

Postoperative complications in transfused patients

Transfused patients had significantly more postoperative issues, including:

• Higher ICU admission rates
• Longer hospital stays (median: 7 vs 4 days)
• Higher rates of:
  • Sepsis
  • Acute kidney injury (AKI)
  • Postoperative bleeding
  • Wound infections
  • Delirium

Implementing patient blood management (PBM)

A structured PBM program can help mitigate risks associated with transfusions. The World Health Organization (WHO) supports global adoption of PBM protocols.

1. Identify and treat preoperative anemia

• Hemoglobin check at least 4 weeks before surgery
• IV or oral iron supplements
• Erythropoiesis-stimulating agents when appropriate

2. Minimize intraoperative blood loss

• Laparoscopic over open surgery where possible
• Use of antifibrinolytics (e.g., tranexamic acid)
• Normothermia to support coagulation

3. Adopt restrictive transfusion thresholds

• Consider transfusion only when Hb < 7 g/dL in stable patients
• Evaluate organ function and perfusion

4. Educate clinicians and patients

• Regular training and awareness programs
• Multidisciplinary teamwork

Conclusion

The ARCA-1 study provides robust, international data demonstrating that perioperative blood transfusions in cancer surgery are associated with significantly worse outcomes, including 1-year mortality, cancer progression, and postoperative complications. The findings advocate for a paradigm shift toward personalized transfusion practices and comprehensive patient blood management strategies.

For patients and providers, the message is clear: Blood is life-saving, but not risk-free. Use it wisely.

Reference: Cata JP et al. The Association Between Perioperative Red Blood Cell Transfusions and 1-Year Mortality After Major Cancer Surgery: An International Multicenter Observational Study. Anesth Analg. 2025;140:782-794.

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AI On Call: Case of the Week

A 67-year-old man is scheduled for elective open colon cancer resection. He has mild anemia (Hb 10.2 g/dL) but is hemodynamically stable. Intraoperatively, his Hb drops to 8.6 g/dL. Should you transfuse?

Here’s what the Anesthesia Assistant recommends doing: