GI Bleeds: Withholding Transfusions Boosts Survival

Yael Waknine

January 04, 2013

Withholding transfusions until hemoglobin levels are lower than 7%, rather than 9%, improves overall survival by 45% in patients with acute upper gastrointestinal (GI) bleeding, according to a study published in the January 3 issue of the New England Journal of Medicine.

"[This study] provides long-awaited evidence to guide practice and justify current recommendations for the management of upper gastrointestinal bleeding," asserts Loren Laine, MD, from the Yale University School of Medicine in New Haven and the VA Connecticut Healthcare System in West Haven, in an accompanying editorial.

Although prior meta-analyses have largely excluded the potential for benefit with a liberal transfusion strategy, only 1% or less of included patients had acute GI bleeds, Dr. Laine writes.

To examine the potential benefit of a more narrow approach, Càndid Villanueva, MD, from the Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de Sant Pau, Autonomous University, and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain, and colleagues consecutively enrolled 921 patients presenting with acute GI bleeds, assigning them to receive red blood cell transfusions according to a restrictive (hemoglobin level, <7 g/dL) or liberal (hemoglobin level, <9 g/dL) strategy. Baseline hemoglobin levels were comparable for the 2 groups of patients (9.6 ± 2.2 g/dL and 9.4 ± 2.4 g/dL, respectively; P = .45).

Results revealed that a restrictive approach to transfusions led to an overall 55% reduction in 45-day mortality rate (95% vs 91%; 95% confidence interval [CI], 33% - 92%; P = .02), which was primarily attributed to fewer deaths from bleeding that could not be successfully controlled (3 [0.7%] patients vs 14 [3.1%] patients; P = .01).

Other benefits included fewer transfusions (49% vs 86%; P < .001), a decreased likelihood of further bleeding (10% vs 16%; hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.43 - 0.91; P = .01), and fewer adverse events overall (40% vs 48%; HR, 0.73; 95% CI, 0.56 - 0.95; P = .02).

Subgroup Analyses

Subgroup analyses revealed that there was a 43% decrease in mortality among patients with cirrhosis (HR, 0.57; 95% CI, 0.30 - 1.08; P = .08), and that improved survival rate was particularly driven by those with Child–Pugh class A or B disease (HR, 0.30; 95% CI, 0.11 - 0.85; P = .02). No such benefit was observed among those with more severe class C disease (HR, 1.04; 95% CI, 0.45 - 2.37; P = .91).

A similar pattern was observed with respect to the risk for further bleeding among patients with cirrhosis in general (12% vs 22%; HR, 0.49; 95% CI, 0.27 - 0.90; P = .02), those with Child–Pugh class A or B disease (11% vs 21%; HR, 0.53; 95% CI, 0.27 - 0.94; P = .04), and patients with class C disease (15% vs 28%; HR, 0.58; 95% CI, 0.15 - 1.95; P = .33).

Although concerns have been raised regarding the risk for rebound increases in portal pressure and related bleeding in patients with cirrhosis who have portal hypertension, patients in the restrictive strategy group experienced no change in the portal pressure gradient from baseline to days 2 or 3, whereas a significant increase was observed among those in the liberal strategy group (20.5 ± 3.1 mm Hg to 21.4 ± 4.3 mm Hg; P = .03).

Patients with cirrhosis who were assigned to the restrictive strategy group were less likely overall to require balloon tamponade or a transjugular intrahepatic portosystemic shunt (2% vs 8% [P = .03] and 4% vs 11% [P = .04]), respectively.

Among patients with variceal and peptic ulcer–related bleeding, the restrictive transfusion strategy showed a trend toward improved survival rates relative to the liberal approach (HR, 0.58 [95% CI, 0.27 -1.27; P = .18] and HR, 0.70 [95% CI, 0.26 - 1.25; P = .26], respectively), as well as toward the likelihood of further bleeding (11% vs 22% [HR, 0.50; 95% CI, 0.23 - 0.99; P = .05] and 10% vs 16% [HR, 0.63; 95% CI, 0.37 - 1.07; P = .09]).

"Largely on the basis of results from studies in animals, a restrictive transfusion strategy is commonly used for patients with variceal bleeding to prevent rebound increases in portal pressure," Dr. Laine writes, noting that although the study authors suggest that the restrictive transfusion strategy's main benefit was observed among patients with rather than without portal hypertension, no formal test of interaction was provided.

Furthermore, hazard ratios for further bleeding and for death were similar in the overall group and in subgroups with cirrhosis, esophageal varices, or peptic ulcer, with closely overlapping confidence intervals, Dr. Laine points out.

However, the study shows merit in it that it reveals benefits for a restrictive transfusion strategy in patients with gastrointestinal bleeding that exceeds that observed in other populations, Dr. Laine suggests, noting the importance of bleeding and mortality as key outcomes.

"[The study] provides important evidence to guide clinical practice," Dr. Laine concludes, advising that most patients with upper GI bleeding, with or without portal hypertension, have blood transfusions withheld until their hemoglobin levels drop below 7 g/dL.

The study was funded in part by the Fundació Investigació Sant Pau. One coauthor reports receiving consulting fees from Sequana Medical. The other authors and the editorialist have disclosed no relevant financial relationships.

N Engl J Med. 2013;368:11-21, 75-76. Article abstract, Editorial extract