Although micronutrient deficiency is the most common etiology of anemia after bariatric surgery, it is important to realize that there are other mediators of anemia as well. Iron deficiency in particular has been described as the most common etiology of anemia after bariatric surgery, although the methodology of some earlier studies has been questioned with specific concern that some investigators failed to properly characterize anemia and definitively demonstrate the presence or absence of iron deficiency [1]. Indeed, a number of studies have reported persistent anemia after the exclusion of iron, folate, and B12 deficiencies [29, 32, 38]. As detailed previously, although prophylactic iron therapy successfully prevented the development of iron deficiency, it did not necessarily reduce the incidence of anemia [18]. While a proportion of such cases could be attributable to deficiencies in less commonly evaluated micronutrients, a number of cases of anemia previously ascribed to micronutrient deficiency may instead be secondary to alternative processes, such as anemia of chronic inflammation [1].

As opposed to the management and prevention of micronutrient deficiency, there is little guidance by way of clinical trials or even expert-driven consensus statements about how or when to further evaluate persistent anemia once the more common nutritional deficiencies have been excluded. Even in the setting of established iron deficiency, practitioners must determine which cases are likely related to maldigestion and malabsorption, and which require evaluation for alternative pathology, particularly chronic blood loss. A logical approach might include evaluation of those patients with clinical evidence of blood loss either grossly or with fecal occult-positive stool, iron deficiency refractory to replacement therapy, recent NSAID use, or associated symptoms including dyspepsia or abdominal pain. In the absence of any data-driven evidence, however, such decisions will continue to fall to the discretion of the individual provider and must be evaluated on a case-by-case basis, taking into account the clinical context and relative index of suspicion.

The implications of when to evaluate for chronic blood loss are not small as investigation of the upper gastrointestinal tract in the post-bariatric surgery patient can pose a number of diagnostic and therapeutic challenges. Doing so requires a thorough understanding of the normal postsurgical anatomy, knowledge of the most frequent complications observed after surgery, and the acquisition of expertise necessary to access portions of the GI tract that are no longer easily evaluated by traditional endoscopy. As mentioned, early bleeding after bariatric surgery is usually related directly to bleeding at a surgical staple site. Late bleeding typically occurs in relation to marginal ulcers at the gastrojejunal anastomosis or, less commonly, ulcers in the gastric remnant or duodenum [39]. It is estimated that marginal ulcers occur in 16–20% of RYGB patients, usually within the first 3 months of ­surgery [40, 41]. In patients with suspicion for blood loss, initial investigation includes traditional esophagogastroduodenoscopy (EGD) to evaluate for sources of bleeding including marginal ulcers, esophagitis, or gastritis. If no source of bleeding is identified, evaluation of the bypassed segment may be necessary [39]. The evaluation and treatment of bleeding sources within the defunctionalized gastric remnant or duodenum however can be challenging. The distance to the jejunojejunal anastomosis in of itself may represent a barrier to successful endoscopic evaluation. This is particularly true as longer Roux limbs of 100–150 cm are utilized in most bariatric centers. In addition, the acute angulation at the site of the jejunojejunal anastomosis can further represent a barrier to successful navigation [6]. Moreover, even when the biliopancreatic limb is accessed successfully, passage of the endoscope all the way to the level of the gastric remnant is not easily accomplished, although some level of success has been described previously with a pediatric colonoscope [6, 42, 43]. For cases where traditional endoscopy is not successful, a few maneuvers have been described to allow access to the gastric remnant and duodenum. Previously, relatively invasive measures have been necessary to achieve this goal including the placement of a percutaneous gastrostomy tube either radiographically or laparoscopically [44]. More recently, developing endoscopic technology and techniques allow the same goal in a less invasive manner. Double-balloon enteroscopy has been utilized with some success as has even newer technology such as the ShapeLock system (ShapeLock endoscopic guide; USGI, San Clemente, CA) [42, 45]. The latter technology, initially investigated as a means of facilitating colonoscopy, utilizes an overtube with an on-demand locking feature that may facilitate advancing an enteroscope to the level of the gastric remnant [46].

Although, the most common source of chronic blood loss after RGYB is marginal or stomal ulceration, it is important to note that the bariatric surgery patient has the same, if not greater, risk for alternative pathology contributing to either upper or lower GI bleeding as the general population. Peptic ulcer disease has been described in the gastric remnant and duodenum after RYGB as have cases of bleeding gastritis [47, 48]. Although less common, gastric cancer within the gastric remnant has even been reported [49]. While focus upon the upper GI tract as a source of blood loss after bariatric surgery is appropriate, it is important not to exclude the lower gastrointestinal tract when evaluating anemia suspicious for chronic blood loss. Relative to the general population, obese patients are at increased risk for colorectal polyps and cancer [50, 51]. Despite this association, obese patients represent a population that undergoes less colorectal cancer screening than the normal weight population [52]. For this reason, all patients over the age of 50 should be brought up to date with regard to routine colorectal cancer screening prior to surgery, and any patients with evidence of iron deficiency at initial evaluation should undergo upper and lower endoscopy before proceeding with bariatric surgery.

Given the potential difficulties in evaluating the diverted upper GI tract in a patient after RYGB, routine preoperative upper endoscopy has been advocated by some groups. While it is universally accepted that patients with evidence of iron deficiency prior to surgery undergo complete endoscopic evaluation to exclude a potential source of GI blood loss, it is less clear if such practice should be routinely extended to all patients. Advocates of routine preoperative upper endoscopy base this argument on a reportedly high prevalence of unexpected findings at EGD in patients prior to RYGB. Gastritis, esopha­gitis, and hiatal hernia have been described most commonly, with less common findings including gastric ulcers, duodenal ulcers, gastric polyps, Barrett’s esophagus, and even gastric cancer [53, 54]. The counter argument against routine endoscopic evaluation has been made that this practice does nothing to address the more challenging postoperative problem of occult GI blood loss which develops only after surgery secondary to inflammation, erosions, or ulceration [51].

Regardless of professional opinion regarding the utility of routine preoperative upper endoscopy, most practitioners do seem to advocate for the routine testing and treatment of active Helicobacter pylori infection. H. pylori is relatively prevalent in the population with morbid obesity, and some evidence exists that preoperative screening for H. pylori may result in decreased rate of marginal ulcer formation [55]. It is worth noting however that this has not been universally replicated as a number of studies have demonstrated no difference in marginal ulcer formation in those tested and treated for H. pylori vs. those not [56, 57]. No randomized clinical trials investigating this or the role of routine preoperative endoscopy have been performed to date.

Finally, in addition to iron deficiency related to altered metabolism and absorption as well as chronic blood loss, there are less common contributors to iron deficiency that, although less frequent, may warrant further consideration depending on the clinical context. One such condition is small intestinal bacterial overgrowth (SIBO). SIBO has been described after RYGB but more frequently is described in association with BPD secondary to stasis of intestinal contents in the biliopancreatic limb. Bacterial overgrowth in the blind limb may result in damage and increased turnover of enterocytes, including their iron stores, as well as direct competition for nutrients [58]. That said, like many aspects of care in the patient having undergone bariatric surgery, evaluation for SIBO may not be straightforward. A great many patients experience symptoms of bloating, nausea, and diarrhea and exhibit evidence of malnutrition after RYGB because of alterations in gastrointestinal anatomy and physiology already reviewed. These clinical features are quite similar to those that evolve with SIBO and are therefore less likely to be helpful for discriminating the presence or absence of bacterial overgrowth. More objective evaluation may also be thwarted as the utility of jejunal aspirates for bacterial count is unknown after bypass surgery, and hydrogen breath testing may be limited as rapid transit through the small bowel may lead to early rises in breath hydrogen, leading to false-positive studies [59]. Biliary scintigraphy with delayed images to outline afferent biliopancreatic limb transit may identify afferent limb stasis which may facilitate bacterial overgrowth. The sensitivity and specificity of these studies are not known. Hence, empiric trial of antibiotics may be necessary if clinical suspicion is high enough to seem warranted.