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628 Part VI: The Erythrocyte Chapter 43: Iron Deficiency and Overload 629

After history and physical examination rule out an obvious bleeding In hereditary hemorrhagic telangiectasia (Chap. 122), character-
source in the genitourinary or respiratory tracts, evaluation of the gas- istic lesions commonly occur on fingertips, nasal septum, tongue, lips,
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trointestinal tract is necessary because of the potential that the patho- margins (helices) of ears, oral and pharyngeal mucosa, palms and soles,
logic process causing the blood loss is life-threatening. In the adult, the and other epithelial and cutaneous surfaces throughout the body. Those
most common causes are peptic ulcer, erosion in a hiatal hernia, gastri- lesions that occur in the gastrointestinal tract are particularly likely to
tis (including that caused by alcohol or aspirin ingestion), hemorrhoids, bleed and to cause iron deficiency.
vascular anomalies (such as angiodysplasia), and neoplasms. Meckel Diverticulum Meckel diverticulum is a very common
Gastritis, Varices, Ulcers, and Inflammation Gastritis as a result abnormality representing a vestigial remnant of the omphalomesenteric
of drug ingestion is a common cause of bleeding. Aspirin, indometha- duct. In children, bleeding from this structure accounts for a small pro-
cin, ibuprofen, and other nonsteroidal antiinflammatory drugs cause portion of cases of iron-deficiency anemia. 29
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gastritis, but may also cause bleeding by inducing gastric or duodenal Genitourinary Tract Heavy menstrual bleeding is a very com-
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ulcers, or lesions in the small intestine and even the colon. Gastri- mon cause of iron deficiency. The amount of blood lost with menstrua-
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tis caused by alcohol ingestion can also cause significant blood loss. tion varies markedly from one woman to another and is often difficult
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Chronic blood loss is often the cause of anemia in rheumatoid arthritis to evaluate by questioning the patient. The average menstrual blood loss
(perhaps because of the use of nonsteroidal antiinflammatory medica- is approximately 40 mL per cycle. Blood loss exceeds 80 mL (equivalent
tions) and in inflammatory bowel disease. to approximately 30 mg of iron) per cycle in only 10 percent of women.
Chronic blood loss from esophageal or gastric varices can lead The volume of blood lost in the course of one menstrual cycle may be
to iron-deficiency anemia. Hemorrhoidal bleeding may lead to severe as high as 495 mL in apparently healthy, nonanemic women who do not
iron-deficiency anemia. Chronic blood loss may result from diffuse regard their menstrual flow to be excessive. The amount of menstrual
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gastric mucosal hypertrophy (Ménétrier disease). Peptic ulcers of the blood lost does not seem to vary markedly from one cycle to another
stomach or duodenum are common causes of iron deficiency, and an for any given individual. Oral contraceptives reduce menstrual blood
association between infection with Helicobacter pylori and iron-deficiency loss, but the use of an intrauterine coil for contraception increases men-
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anemia has been documented in numerous studies. Some of these strual blood loss, especially during the first year of use. Because the daily
iron-deficient patients who are infected with H. pylori do not respond dietary intake is usually between 10 and 12 mg of iron and only a few
to oral iron alone, but do respond to eradication of H. pylori. 15 milligrams of this can be absorbed, iron balance in many menstruating
Gastric ulceration and bleeding can also occur in disorders of women is precarious.
hypergastrinemia, as in Zollinger-Ellison syndrome and pseudo–Zoll- Excessive bleeding may be caused by uterine fibroids and malig-
inger-Ellison syndrome. Although concerns were raised that long-term nant neoplasms. Neoplasms, stones, or inflammatory disease of the kid-
medical therapy of these disorders with proton pump inhibitors would ney, ureter, or bladder may cause enough chronic blood loss to produce
also cause iron deficiency by raising gastric pH and making iron less iron deficiency.
soluble, this does not seem to be the case. Anemia that follows subtotal In the absence of hematuria, urinary iron losses as high as 1 mg/day
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gastrectomy is usually attributed to reduced absorption of dietary iron have been reported in rare patients with nephrotic syndrome, some of
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(see “Malabsorption of Iron” below), but occult intermittent gastroin- whom had hypoferremia and hypochromic anemia. We found only
testinal bleeding from gastrointestinal lesions may also be a contribu- one report of a patient in whom abnormally high urinary iron loss may
tory factor, and requires endoscopic evaluation. 17 have caused anemia without proteinuria or hematuria. 33
Diaphragmatic Hernia Diaphragmatic (hiatal) hernia is often Bleeding Disorders Hemostatic defects, particularly those related
associated with gastrointestinal bleeding. 18–20 The frequency of anemia to abnormal platelet function or number may lead to gastrointestinal
ranges from 8 to 38 percent. Bleeding is much more likely to occur in bleeding, although unless the thrombocytopenia or platelet dysfunction
patients with paraesophageal or large hernias than in those with sliding is severe, gastrointestinal bleeding usually signifies an abnormality in
or small hernias. Mucosal changes cannot always be demonstrated by the gastrointestinal tract. Gastrointestinal bleeding is common in von
esophagoscopy or gastroscopy in patients who have had blood loss from Willebrand disease (Chap. 126), but often because of coexistent peptic
hiatus hernia. However, a linear gastric erosion, also called a “Cameron ulcer disease. Polycythemia vera is typically associated with iron defi-
ulcer,” commonly occurs on the crests of mucosal folds at the level of the ciency as a result either of spontaneous gastrointestinal hemorrhage
diaphragm, and appears to be the site of bleeding. 21 that commonly occurs in this disorder, or phlebotomy therapy, or both
Intestinal Parasitism Hookworms are a major cause of gastroin- (Chap. 84).
testinal blood loss in many parts of the world. 22 When a patient with a disorder of hemostasis suffers from gastro-
Vascular Anomalies The lesions of angiodysplasia may occur intestinal bleeding, one must consider the possibility that the bleeding
in any part of the gastrointestinal tract. These tiny vascular anom- may not be caused by a hemostatic defect alone, but that an anatomic
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alies may be the cause of significant blood loss. Endoscopy is usually lesion of the gastrointestinal tract may also be present.
required for diagnosis, and often needs to be repeated as bleeding can Nosocomial (Iatrogenic) Anemia Iatrogenic anemia is particu-
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be intermittent. Gastric antral vascular ectasia exhibits a characteristic larly prevalent in intensive care units where repetitive blood sampling
endoscopic appearance (“watermelon stomach”), and is another cause may result in removal of 40 to 70 mL of blood daily, and this iatrogenic
of blood loss. Hemorrhage into the biliary tract is a rare cause of chronic phlebotomy can result in iron-deficiency anemia.
iron-deficiency anemia. 25 The use of extracorporeal dialysis for treatment of chronic renal
Tortuous, dilated sublingual venous structures, the cherry heman- disease may cause iron deficiency, 35,36 often superimposed upon the ane-
giomas commonly seen in the elderly, and the spider telangiectases of mia of chronic renal disease (Chap. 37). Patients treated with chronic
chronic liver disease are usually easily distinguished from the lesions of hemodialysis experience multiple sources of blood loss with the dialysis
hereditary hemorrhagic telangiectasia. Bleeding from intestinal telangiec- equipment is a major cause, along with gastrointestinal bleeding, blood
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tases has also been observed in scleroderma and in Turner syndrome, sampling and bleeding related to vascular access.
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as a manifestation of bleeding from abnormal blood vessels. Cutaneous Anemia Incident to Blood Donation Each whole-blood dona-
hemangiomas (blue rubber bleb nevus) may be associated with hemor- tion removes approximately 200 mg of iron from the body. Lesser
rhage from intestinal hemangiomas. 28 amounts of iron are removed in the course of donating platelets or

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