Blood Tests used in the Diagnosis of Crohn’s Disease
Acute-Phase Reactants in the Diagnosis of Crohn’s Disease
C-reactive protein (CRP), an acute-phase protein
produced by the liver, was first identified in 1930 as a substance
in the serum of patients with pneumonia. Levels of this protein rise
rapidly during inflammatory processes in the body and fall rapidly
once inflammation is quiescent, making CRP a valuable tool for monitoring
disease activity in some diseases. CRP response is strong with some
diseases (e.g., Crohn’s disease [CD], rheumatoid arthritis)
and not as reliable with other diseases (lupus, dermatomyositis, ulcerative
colitis [UC]). In a study of 100 patients with CD and 43 patients
with UC, Solem and colleagues concluded that CRP elevation correlated
well with disease activity in endoscopic and histologic inflammation
in patients with CD, but not with radiologic findings. In patients
with UC, CRP elevation was associated with clinical disease activity,
elevated erythrocyte sedimentation rate (ESR), anemia, hypoalbuminemia,
and mucosal inflammation. Elevation in CRP was not associated with
histologic inflammation in UC, although the sample size was small
and, therefore, subject to a
Elevation in ESR is another nonspecific indication of inflammation. In the presence of inflammation, high concentration of fibrinogen causes red blood cells (RBCs) to stick together, allowing them to settle more quickly than when inflammation is not present. ESR is reported in millimeters per hour, the speed at which the cells fall. As with CRP, ESR elevations are not as consistent in UC as they are in CD. In addition, levels remain elevated for a prolonged period of time, making this laboratory test less useful for monitoring acute disease activity or response to therapy.
Serum Markers Used in the Diagnosis of Crohn’s Disease
Serologic markers may be useful in identifying inflammatory bowel disease (IBD) and in differentiating between CD and UC. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) is expressed in a high percentage of patients with UC and in 10% to 30% of patients with CD affecting the colon.2699 In contrast, anti-Saccharomyces cerevisiae antibodies (ASCA) are associated with CD in that the antibody is expressed in 50% to 70% of patients with CD. First reported by Saxon, et al., in 1990, p-ANCA was determined by a newly developed enzyme-linked immunosorbent assay (ELISA) technique. Investigators concluded that the assay was associated with 84% sensitivity in a cohort of 25 patients with confirmed diagnosis of UC.2018 An additional early trial was conducted, screening sera from 34 patients with confirmed UC and 30 patients with CD. Rump, et al., used the p-ANCA ELISA screen developed by Saxon and colleagues, in addition to ELISA for antibodies against antiproteinase-3 and Hep-2 cells for antinuclear and anticytoplasmic antibodies. Sera from UC patients tested positively for p-ANCA, while reaction to other antibodies was either absent or weak, leading the authors to conclude that p-ANCA may help to differentiate between UC and CD.2019 Following these landmark studies, testing for ASCA and p-ANCA became commercially available and numerous studies have been conducted to determine the reliability of these tests for initial diagnosis and differentiation between subtypes of IBD. A 1996 meta-analysis, conducted by Reese and colleagues, included 3,841 UC and 4,019 CD patients from 60 studies and used metaregression to determine the effect of age, deoxyribonucleic acidase (DNA), colonic activity, and assay type. Investigators determined that ASCA+, p-ANCA- results offered 54.6% sensitivity and 92.8% specificity for CD. p-ANCA+ results were consistent with 55.3% sensitivity and 88.5% specificity for the population with UC. Sensitivity and specificity was improved in a subset of pediatric patients.2020 While the high specificity of these tests is potentially helpful in distinguishing between forms of IBD, their relatively low sensitivity precludes their ability to replace clinical, radiologic, endoscopic, and histologic diagnosis of both CD and UC.
Other Blood Tests in Crohn’s Disease
Routine hematologic tests may raise the suspicion of IBD but lack the specificity needed for confirmation. Routine screening of individuals presenting with symptoms suggestive of IBD may reveal abnormalities in some, but not all, patients eventually diagnosed with either CD or UC.
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White blood count
The absolute white blood count (WBC) may be elevated in both UC and CD. In many patients, the absolute WBC is not elevated, but there may be an increased number of immature neutrophils, also called a "left shift."
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Platelet count
Thrombocytosis is an acute phase reactant in the presence of inflammation. Platelet counts may also be elevated in a number of other disease states and in the presence of bleeding, making this laboratory finding unreliable as a measure of disease activity. In contrast, mean platelet volume, which accounts for platelet size, is decreased in IBD, leading one group of researchers to conclude that mean platelet volume is a useful marker of disease activity in both UC and CD.2021
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Albumin
Serum levels of albumin decrease in patients with active IBD. The cause of hypoalbuminemia in IBD can result from loss from the gastrointestinal tract, malnutrition, inflammation, or a combination of factors. Hypoalbuminemia is also seen in a number of other diseases, including nephrotic syndrome, liver disease, congestive heart failure, and hemorrhage; therefore, it is not specific to IBD. Although not specific for IBD, hypoalbuminemia may be an important predictor for failure of medical therapy in children with CD.11444 To date, there are no reports regarding hypoalbuminemia and outcomes in UC.
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Red blood cell count, hemoglobin, and hematocrit
Indicators of the overall number of RBCs and their function can be helpful in monitoring disease activity. Anemia is a consistent clinical feature of IBD,2023 although it can occur for a variety of reasons. Decreased RBC count and hemoglobin and hematocrit levels can be seen with blood loss, nutritional deficiency (e.g., vitamin B12, folate), and bone marrow suppression, all of which are risks associated with IBD. Medications commonly used to treat IBD have been associated with an increase in the risk of folate deficiency and are associated with bone marrow suppression. Malabsorption associated with CD predisposes individuals to deficiencies in vitamin B12 and folate. If anemia is present, further diagnostic evaluation is needed to identify the cause.
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Iron indices
Iron deficiency anemia is an important and consistent complication of IBD and occurs when intestinal blood loss is not matched by iron absorption in the duodenum. The limited iron supply is detrimental to developing erythroblasts, resulting in stimulation of erythropoiesis, which creates an even greater demand for iron, the supply of which is depleted.2023 In iron deficiency, serum levels of iron and ferritin are low and total iron binding capacity (TIBC) is high, reflecting efforts to produce more transferrin to bind available iron.
In addition to iron deficiency anemia, IBD predisposes individuals to anemia of chronic disease. In the presence of inflammation, anemia of chronic disease occurs through several cytokine-driven mechanisms, including diversion of iron traffic, inhibition of erythroid progenitor proliferation and differentiation, blunted erythropoietin response, and diminished erythrocyte life cycle.2023 While serum iron level is low, ferritin is often normal or high and TIBC is low or normal in individuals with anemia of chronic disease.
Content on this page was last reviewed on October 31, 2009.
Content on this page was last changed on March 25, 2009.
References:| 2014. | Solem CA, Loftus EV, Tremaine WJ, et al. Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease. Inflamm Bowel Dis. 2005;11(8):707-712. |
| 2015. | Vermeire S, Van Assche G, Rutgeerts P. C-reactive protein as a marker for inflammatory bowel disease. Inflamm Bowel Dis. 2004;10(5):661-665. |
| 2018. | Saxon A, Shanahan F, Landers C, Ganz T, Targan S. A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol. 1990;86(2):202-210. |
| 2019. | Rump JA, Schölmerich J, Gross V, et al. A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn’s disease. Immunobiology. 1990;181(4-5):406-413. |
| 2020. | Reese GE, Constantinides VA, Simillis C, et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006;101(10):2410-2422. |
| 2021. | Kapsoritakis AN, Koukourakis MI, Sfiridaki A, et al. Mean platelet volume: a useful marker of inflammatory bowel disease activity. Am J Gastroenterol. 2001;96(3):776-781. |
| 2023. | Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut. 2004;53(8):1190-1197. |
| 2699. | Batres LA, Baldassano RN. Evaluation of the patient suspected of having inflammatory bowel disease. In: Lichtenstein G, ed. The Clinician’s Guide to Inflammatory Bowel Disease. Thorofare, NJ: Slack Inc.; 2003:315-323. |
| 11444. | Gupta N, Cohen SA, Bostrom AG, et al. Risk factors for initial surgery in pediatric patients with Crohn’s disease. Gastroenterology . 2006;130(4):1069-1077. |
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