Hematologic Manifestations of Inflammatory Bowel Disease
Anemia in Inflammatory Bowel Disease Patients
Anemia is a common manifestation of inflammatory bowel disease (IBD) and may be caused by chronic blood loss (iron deficiency), folic acid deficiency, vitamin B12 deficiency (especially in patients with ileal resections), chronic inflammation (anemia of chronic disease), or the use of marrow-suppressing medications. Iron deficiency anemia occurs because inflammation and ulceration, which are prominent pathophysiologic effects of IBD, result in gastrointestinal blood loss. Although iron absorption tends to be normal in patients with ulcerative colitis and Crohn’s disease, iron loss may exceed the patient’s capacity for iron absorption.2896, 11700
Anemia of Chronic Disease in Inflammatory Bowel Disease
Anemia of chronic disease (ACD) is seen often in inflammatory bowel disease (IBD). The term ACD was first used by Cartwright in 1966, although the relationship between the production of inflammatory cytokines and erythropoiesis was not yet understood. Currently, 3 mechanisms have been elucidated:9772
-
Functional iron deficiency that results from iron withholding from the plasma with inadequate delivery to the bone marrow mediated mostly by interleukin-1 (IL-1) and tumor necrosis factor-α (
TNF-α ) -
Direct inhibition of erythropoiesis (blast-forming unit-E) and colony-forming unit-E mediated by interferon-γ
-
Inhibition of erythropoietin production mediated by IL-1,
TNF-α , and IL-6.
Prevalence of Anemia in Inflammatory Bowel Disease
Wilson, et al, reviewed all published data on the prevalence of anemia in patients with inflammatory bowel disease (IBD).2896 Nine studies examined the prevalence of anemia in Crohn’s disease (see Fig.640), 5 in ulcerative colitis (see Fig.641), and 3 in IBD (see Fig.642). Overall prevalence of anemia ranged from 8.8%-73.7%.
Figure 640 – Prevalence of Anemia Patients With Crohn’s Disease
Table 1, Page 46S, Am J Med. 2004;116:(Suppl 7A):44S-49S is used with permission of Elsevier Inc. All rights reserved..
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Figure 641 – Prevalence of Anemia in Patients with Ulcerative Colitis
Table 2, Page 47S, Am J Med. 2004;116:(Suppl 7A):44S-49S is used with permission of Elsevier Inc. All rights reserved.
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Figure 642 – Prevalence of Anemia in Patients with Undifferentiated Inflammatory Bowel Disease
Table 3, Page 47S, Am J Med. 2004;116:(Suppl 7A):44S-49S is used with permission of Elsevier Inc. All rights reserved.
Some figures may not display clearly when rendered as a PDF or printed.
Autoimmune Hemolytic Anemia and Inflammatory Bowel Disease
Although autoimmune conditions often coexist, reports of autoimmune hemolytic anemia (AIHA) in association with ulcerative colitis and Crohn’s disease (CD) are rare. Until December 2006, only 4 cases of CD and AIHA had been reported in the literature.2962, 2974, 3000, 3006 For ulcerative colitis and AIHA, fewer than 50 cases have been reported in the literature. Little is known about the pathogenic association of AIHA and inflammatory bowel disease, although the clinical course of one disease does not seem to follow the other.2991
Idiopathic Thrombocytopenia Purpura and Inflammatory Bowel Disease
Thrombocytopenia in inflammatory bowel disease (IBD) can be immune-mediated or treatment-related. Idiopathic thrombocytopenic purpura (ITP) or immune thrombocytopenia is thought to be caused by antibodies to platelet membrane antigens and is rarely reported in association with IBD. However, there have been case reports of laboratory findings consistent with ITP in a patient with ulcerative colitis (UC)2902 and in another with Crohn’s disease (CD),10318, 2945 as well as a review of 22 cases in the literature (19 patients with UC, 3 with CD).3040 Little is known about the association of ITP and IBD, and the pathogenesis is poorly understood. It has been hypothesized that molecular mimicry may play a role in ITP associated with IBD, but little data exist to support it.3040
Thrombotic thrombocytopenic purpura has rarely been reported in conjunction with IBD. As with ITP, very little is known about this association.3015, 2927
Thromboembolism in Inflammatory Bowel Disease
Thromboembolism is a common and well established extra-intestinal manifestation of inflammatory bowel disease (IBD). Both arterial and venous systems may be involved. Patients with IBD appear to have a 3- to 4-fold increase in risk of developing thromboembolism compared to a normal population. The frequency of thromboembolic events in the IBD population varies per study and ranges from 2%-10%. Mortality has been reported between 8%-25% during an acute episode, and there are risks of recurrence. In contrast to thrombocytopenia and autoimmune hemolytic anemia, there seems to be a correlation between the degree of IBD activity and the risk of thromboembolic events. In addition to mucosal inflammation, other factors, such as immobility, surgery, and use of central venous catheters, may also increase the risk of thromboembolism. 3007, 11701, 11702 Thromboembolism is a frequent complication of hospitalized IBD patients, and has been found to lead to higher mortality rates.11703, 11704
Deficiency of vitamins B6 and B12 and folate are commonly associated
with acquired hyperhomocysteinemia, a condition that may also increase
the risk of thrombosis. Erzin, et al conducted a prospective study
to identify the prevalence and risk factors of hyperhomocysteinemia
and its correlation with prior thromboembolic events in a cohort of
IBD patients who had not undergone intestinal resections.11705 Concentrations
of homocysteine, cobalamin, folate, and pyridoxine were analyzed in
105 consecutive patients with IBD. Eleven of these patients had a
history of thromboembolic complications. A cohort of 85 healthy volunteers
were matched for age and sex and served as controls. Homocysteine
concentrations in patients with IBD were significantly higher than
those of the control subjects [
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| 2902. | Hisada T, Miyamae Y, Mizuide M, et al. Acute thrombocytopenia associated with preexisting ulcerative colitis successfully treated with colectomy. Intern Med. 2006;45(2):87-91. |
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| 2945. | Boyne MS, Dye KR. Crohn’s colitis and idiopathic thrombocytopenic purpura. Postgrad Med J. 2000;76(895):299-300. |
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| 3000. | Ng JP, Soliman A, Kumar B, Lam DC. Auto-immune haemolytic anaemia and Crohn’s disease: a case report and review of the literature. Eur J Gastroenterol Hepatol. Apr 2004;16(4):417-419. |
| 3006. | Plikat K, Rogler G, Scholmerich J. Coombs-positive autoimmune hemolytic anemia in Crohn’s disease. Eur J Gastroenterol Hepatol. 2005;17(6):661-666. |
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| 3040. | Zlatanic J, Korelitz BI, Wisch N, et al. Inflammatory bowel disease and immune thrombocytopenic purpura: is there a correlation? Am J Gastroenterol. 1997;92(12):2285-2288. |
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| 10318. | Kuloglu Z, Kansu A, Demirceken F, Ileri T, Ertem M, Girgin N. The association of chronic recurrent immune thrombocytopenic purpura and Crohn’s disease. Inflamm Bowel Dis . 2005;11(10):950-951. |
| 11700. | Gisbert J, Gomollon F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol . 2008;103(5):12991–12307. |
| 11701. | Freeman HJ. Venous thromboembolism with inflammatory bowel disease. World J Gastroenterol . 2008;14(7):991-993. |
| 11702. | Bernstein CN, Wajda A, Blanchard JF. The incidence of arterial thromboembolic diseases in inflammatory bowel disease: a population-based study. Clin Gastroenterol Hepatol . 2008;6(1):41–45. |
| 11703. | Koutroubakis IE. Venous thromboembolism in hospitalized inflammatory bowel disease patients: the magnitude of the problem is staggering. Am J Gastroenterol . 2008;103(9):2281–2283. |
| 11704. | Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol . 2008;103(9):2272–2280. |
| 11705. | Erzin Y, Uzun H, Celik AF,Aydin S, Dirican A, Uzunismail H. Hyperhomocysteinemia in inflammatory bowel disease patients without past intestinal resections. J Clin Gastroenterol . 2008;42(5):481–486. |
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