Hospital-associated venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality, accounting for 100,000 to 200,000 deaths each year. “About two-thirds of hospital-acquired VTE cases are considered preventable,” says Ruchika Goel, MD, MPH. “An increasing number of studies has suggested that red blood cell (RBC) transfusions—which commonly occur when patients have surgery—may have a role in the development of VTE.”

 

New Data

Few analyses have set out to specifically assess the role of perioperative RBC transfusions in developing postoperative VTE among patients undergoing general surgery or other subspecialty operations. To address this research gap, a study by Dr. Goel, Aaron A. R. Tobian, MD, PhD, and colleagues was conducted to examine if there was association between RBC transfusions given before, during, and after surgery and development of new VTE within 30 days of a surgical procedure. The study, published in JAMA Surgery, used a large prospective, multicenter registry of 525 teaching and nonteaching hospitals in North America. Participants included patients who underwent a surgical procedure in 2014.

“In our study of more than 750,000 surgical patients, we found that RBC transfusions were associated with a two-fold increased risk of a thrombotic event,” says Dr. Tobian. The overall rate of postoperative VTE was 0.8% among patients who received at least one perioperative RBC transfusion. Perioperative RBC transfusion was associated with higher adjusted odds ratios (aOR) of VTE (aOR, 2.1), DVT (aOR, 2.2), and PE (aOR, 1.9) regardless of whether patients had other various putative risk factors.

The study also found that VTE risk continued to rise as the number of intraoperative and/or postoperative RBC transfusion events increased. When compared with no intraoperative or postoperative RBC transfusion, the aOR was 2.1 for patients requiring one transfusion and jumped to 3.1 for those requiring two RBC transfusions and 4.5 for those receiving three or more RBC transfusions. In subgroup analyses, the association between any perioperative RBC transfusion and postoperative VTE remained statistically significant across all surgical subspecialties analyzed in the study. Surgical subtypes included general, neurologic, cardiothoracic, orthopedic, vascular, gynecologic, and urologic surgery. In separate multivariable models, any perioperative RBC transfusion remained significantly associated with developing postoperative DVT and PE (Table). “Our findings are robust considering that the risk of a thrombotic event continued to increase with rising numbers of transfusions,” adds Dr. Tobian.

 

Assessing Implications

According to Dr. Tobian, results of the analysis further support the concept of perioperative RBC transfusions being associated with the development of new or progressive VTE. “Our study demonstrates that there may be additional risks to blood transfusions that are not generally recognized in the community,” he says. Dr. Goel adds that the findings reinforce the importance of following rigorous perioperative patient blood management practices and limiting RBC transfusions to only when necessary. “Every effort should also be made to correct preoperative anemia whenever possible using non-transfusion alternatives like iron and erythropoietin,” she adds. “Ultimately, the goal should be to limit transfusions before, during, or after surgery whenever possible to ensure patient safety.”

Indications for RBC transfusion, such as hemodynamics, symptoms, and hemoglobin and/or hematocrit levels, may be contributors to VTE, and this information was not known in the study. “Our study was a retrospective cohort analysis, and additional research and prospective evaluation is need to confirm and validate our results,” Dr. Tobian says. Future studies should consider these data in the context of additional potential confounders, such as concurrent medication use (eg, VTE prophylaxis) and family history of VTE or an underlying thrombophilia.

References

Goel R, Patel EU, Cushing MM, et al. Association of perioperative red blood cell transfusions with venous thromboembolism in a north American registry. JAMA Surg. 2018 Jun 13 [Epub ahead of print]. Available at: https://jamanetwork.com/journals/jamasurgery/fullarticle/2683886

Litvinov RI, Weisel JW. Role of red blood cells in haemostasis and thrombosis. ISBT Sci Ser. 2017;12:176-183.

Byrnes JR, Wolberg AS. Red blood cells in thrombosis. Blood. 2017;130:1795-1799.

Uhl L, Assmann SF, Hamza TH, Harrison RW, Gernsheimer T, Slichter SJ. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood. 2017;130:1247-1258.