Transfusion Thresholds in Gastrointestinal Bleeding
- Describe risk factors for poor outcome in patients with gastrointestinal bleeding.
- Understand recommended blood transfusion thresholds for gastrointestinal bleeding.
- Recognize circumstances in which restrictive transfusion thresholds may not be appropriate.
- Review an algorithm for the initial management of patients with gastrointestinal bleeding.
Case & Commentary—Part 1
A 70-year-old man with severe, refractory Crohn disease was admitted for management of abdominal pain and high stool output from his ileostomy. He was admitted to the medicine service and initially treated with steroids. On the third day of hospitalization, the patient developed bloody ostomy output. Over the course of the night, his blood pressure began to drop. He was given 2 liters of normal saline with some improvement in his blood pressure. He continued to pass blood and clots from his ostomy, and his hemoglobin fell.
Gastrointestinal hemorrhage is a common cause of morbidity and mortality in the United States, accounting for more than 500,000 hospital admissions and 10,000 inpatient deaths annually. In 2012, there were close to 100,000 hospitalizations for inflammatory bowel disease (IBD), more than 60,000 of which were for Crohn disease. In-hospital deaths were rare, occurring in only 0.3% of admissions.(1) However, brisk gastrointestinal bleeding (GIB) in patients with IBD is associated with a mortality rate of up to 3%.(2,3)
Gastrointestinal bleeding can be divided into upper GIB, middle GIB (bleeding between the ligament of Treitz and the colon), and lower GIB or bleeding from the colon. Common causes of upper GIB include erosive disease, ulcers, varices, and angioectasias.(4) Common causes of lower GIB include diverticulosis, ischemic colitis, hemorrhoids, polyps or neoplasms, and angioectasias.(5)
Mild, chronic bleeding is more common than severe, acute bleeding in patients with IBD. The incidence of severe bleeding in patients with Crohn disease is thought to range from 0.6% to 4%.(6) However, data regarding severe bleeding in IBD is limited to case reports and case series. Bleeding typically arises from the ileum or colon. It can be difficult to identify a single source of bleeding, and blood loss is often attributed to diffuse disease.(7) IBD patients with severe bleeding often require surgery and are at high risk for rebleeding.(2)
The history and physical examination can help to elucidate the site of bleeding as well as to risk stratify the patient. The history should include color, volume, and frequency of bleeding, a review of comorbid conditions, and an inventory of medications, particularly antiplatelet and anticoagulant medications. Physical examination should begin with a review of vital signs, as the presence of positive orthostatics, tachycardia, and hypotension generally reflect a more brisk bleed.
Laboratory evaluation should include a complete blood count, comprehensive metabolic panel, coagulation studies, and blood typing and screening.(8) While monitoring hemoglobin is essential in GIB, it should be noted that in a brisk bleed, hemodynamic instability can be a more sensitive marker of blood loss than hemoglobin level. This is because there can be a delay in hemoglobin drop due to a loss of whole blood with delayed intravascular expansion.
Clinical factors that point to the upper track being the source of a GIB include melena, nasogastric lavage with blood or coffee grounds, and a blood urea nitrogen (BUN) to creatinine ratio of more than 30. The presence of blood clots in the stool decreases the likelihood of upper GIB.(9) However, in some cases, particularly those with brisk hematochezia, it can be difficult to determine the source; 15% of patients felt initially to have lower GIB are ultimately diagnosed with an upper GI source.(10) Therefore, a nasogastric lavage or urgent upper endoscopy is recommended in these patients to exclude an upper GI source.(11)
In patients with GIB, it is important to identify high-risk patients who benefit from closer monitoring, more aggressive resuscitation, and early interventions. Risk scores used in upper GIB include the AIMS65, Glasgow-Blatchford, and Rockall scores.(12-14) Factors associated with higher mortality include advanced age, comorbidities, presentation with melena, onset of bleeding while hospitalized, tachycardia, hypotension, altered mental status, and laboratory abnormalities such as elevated BUN, low albumin, and anemia. There also have been a number of risk factor models for poor outcomes in patients with presumed lower GIB. The largest study identified multiple comorbidities, syncope, the absence of abdominal tenderness and diarrhea, nonsteroidal anti-inflammatory drug or antiplatelet use, hypotension, and hypoalbuminemia as risk factors for severe lower GIB.(15) Ongoing hematochezia has also been identified as a risk factor for severity.(16,17)
In this case, the presence of multiple high-risk factors—including onset of bleeding while hospitalized, older age, comorbid disease, hypotension, ongoing bleeding, and failure to adequately respond to IV fluids—should have alerted the clinician to the potentially seriousness of the bleeding. The assumption that most bleeding in IBD is mild may have led the clinician to downplay these signs of serious bleeding. In addition, the presence of altered anatomy, in this case an ileostomy, may make it difficult to predict the location of bleeding because of more rapid transit of blood.
At this point, it would have been appropriate for the clinician to consider transferring the patient to an intensive care setting and to contact the gastroenterologist on call. The input of interventional radiology and surgery also may have been helpful in the event that endoscopy failed to identify and treat the source of bleeding. Indeed, small bowel sources of bleeding are generally more difficult to localize and treat than upper or lower GI sources. A nasogastric lavage might have been used to help determine if this was a brisk upper GIB versus a small bowel bleed, although the presence of clots suggests a more distal source.
Case & Commentary—Part 2
The overnight hospitalist evaluated the patient but decided not to administer a blood transfusion because the patient's hemoglobin was still above the restrictive hemoglobin transfusion threshold of 7.0 g/dL (which has been supported by the literature and promoted as a quality standard). However, the hospitalist failed to recognize the briskness of the patient's blood loss. Several hours later, the patient passed even more blood through his ostomy. Repeat vital signs revealed profound hypotension and tachycardia. Eventually, he lost his pulse and, despite aggressive attempts at resuscitation, the patient died.
The first step in the management of a GIB is administration of IV fluids to maintain or achieve hemodynamic stability.(18) In the setting of upper GIB, initiation of proton pump inhibitors (PPIs) is generally recommended. Although early initiation of PPI therapy has not been shown to reduce mortality, rebleeding, or surgery, its use has been associated with a decrease in high-risk endoscopic findings and need for endoscopic therapy at index endoscopy.(19) While specific medications are typically not indicated at the time of onset of mid-bowel or lower GIB, initiation of PPI therapy may be prudent in patients with brisk hematochezia until the source of bleeding has been determined.
While historically hemoglobin transfusion thresholds were in the 9–10 g/dL range, studies conducted over the past decade have shown a decreased risk of mortality, rebleeding, and adverse events with a transfusion threshold of 7 g/dL in most patients with upper GIB.(20) However, it is important to note that the results of these studies do not apply to all patients. The largest single center trial excluded patients with massive exsanguinating bleeding, lower GIB, acute coronary syndrome, symptomatic peripheral vasculopathy, stroke, transient ischemic attack, recent transfusion, and recent trauma or surgery.(20) In addition, all patients underwent upper endoscopy within 6 hours of presentation, with treatment of bleeding sources as indicated. A multicenter, open label, cluster-randomized feasibility trial included patients with preexisting comorbidities. In a subanalysis of patients with ischemic heart disease, 28-day mortality was higher in those transfused using a restrictive versus liberal strategy (12% vs. 3%).(21) Therefore, although restrictive transfusion has been applied broadly to GIB, available data supports the use of restrictive transfusion only in patients without massive hemorrhage or certain comorbidities.
The case above illustrates the need to modify standard protocols according to the needs of the individual patient. While restricted transfusion is supported by the literature and has been incorporated into guidelines, it is important to recognize when clinical circumstances necessitate deviation from a standard approach. In this case, the patient showed signs of massive bleeding, therefore he was not an appropriate candidate for the restrictive strategy. In such cases, the hemoglobin tends to fall precipitously and waiting can result in delayed and insufficient resuscitation. In addition, most of the patients included in studies of restrictive transfusion thresholds had upper GIB due to ulcers, varices, or erosive disease—sources that are amenable to endoscopic treatment and/or responsive to PPIs. Furthermore, these patients underwent urgent upper endoscopy with endoscopic treatment of stigmata of hemorrhage. This patient, on the other hand, was likely to have small bowel bleeding from a deep, inflammatory bowel disease—related ulcer. This location and source are challenging to treat endoscopically, meaning that angiography and/or surgery may be necessary to address ongoing bleeding.
Implementation of protocols can help physicians meet quality standards. However, this case demonstrates that strict adherence to such protocols may not be appropriate for all patients. Educating physicians about the limitations of these templates is an important part of their utilization. Electronic health records provide templates for care and play a significant role in patient safety. Flags could be created to alert physicians to clinical situations to which these templates may not apply, including cases in which clinical judgment may prompt us to deviate from guidelines and protocols. Well-constructed and nuanced algorithms can be helpful in guiding physician decision making. For example, a transfusion algorithm might alert physicians of circumstances in which a higher transfusion threshold is recommended. Such algorithms could also indicate the need for intensive monitoring and specialist consultation.
- Although bleeding in inflammatory bowel disease is typically mild, severe bleeding can occur and is associated with a higher mortality, rebleeding, and need for surgery.
- Risk stratification and the use of risk scores may help to identify patients at risk for severe bleeding and the need for higher levels of care and early involvement of consultants.
- Restrictive transfusion protocols have been shown to decrease mortality, rebleeding, and adverse events in certain patients with upper gastrointestinal bleeding.
- However, strict adherence to restrictive transfusion protocols may not be appropriate for all patients, particularly those with brisk bleeding and major comorbidities.
- Early involvement of consulting services can be particularly helpful in patients with atypical presentations.
Lisa Strate, MD, MPH Division of Gastroenterology University of Washington Harborview Medical Center Seattle, WA
Sophia Swanson, MD Division of Gastroenterology University of Washington Harborview Medical Center Seattle, WA
Faculty Disclosure: Drs. Strate and Swanson have declared that neither they, nor any immediate member of their families, have a financial arrangement or other relationship with the manufacturers of any commercial products discussed in this continuing medical education activity. In addition, the commentary does not include information regarding investigational or off-label use of pharmaceutical products or medical devices.
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