Iron deficiency anemia

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Iron deficiency anemia

• Morey Blinder
• Nov. 3, 2006
• Hematology-Oncology Grand Rounds

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Body Iron Distribution and Storage
Duodenum
Dietary iron
(average, 1 - 2 mg
Utilization
Utilization
per day)
Plasma
(TIBC)
transferrin
(3 mg)
Bone
Muscle
marrow
(myoglobin)
(300 mg)
Circulating
(300 mg)
erythrocytes
Storage
(hemoglobin)
iron
(Ferritin)
(1,800 mg)
Sloughed mucosal cells
Desquamation/Menstruation
Other blood loss
(average, 1 - 2 mg per day)
Reticuloendothelial
Liver
macrophages
(1,000 mg)
Iron loss
(600 mg)
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Iron deficiency in the United States
National Health and Nutrition Examination Survey
(NHANES) Survey of sample US households
ferritin, saturation, FEP
MMWR 51(40) 897-9
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Case report

• Case 1 SA
• 19 year old WF student present to the Student
  Health Service with increased fatigue malaise.
• No bleeding and menstrual cycles normal.
• CBC Hgb 7.0 Hct 22.8 WBC count 5,000 platelet
  count count 285,000 MCV 72 retic count 1.1
• Ferritin lt 4 vitamin B12 and folate normal

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Case report

• Case 2 KK
• 70 year old white female noted to have anemia in
  2004 with pre-op evaluation for eye surgery
• GI evaluation normal responded to oral iron
• May 2006 increased fatigue found to have Hgb 6.6
  Hct 22.2 WBC count 7,100 platelet count
  423,000
• Ferritin lt 4 vitamin B12 and folate normal

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Case report

• Case 3 KH
• 43 year old WF had gastric bypass surgery in 1999
  for weight of 340 lbs. Noted to be iron deficient
  in 2004 with partial response to oral iron.
• No bleeding and no menstrual cycles.
• CBC Hgb 9.8 Hct 31.4 WBC count 5,600 platelet
  count 341,000 MCV 67
• Ferritin 13 9 saturated vitamin B12 and
  folate normal

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Case report

• Case 4 ES
• 75 year old WF persistently anemic since 2000.
  Has received 5 units RBCs since 2005.
• No bleeding and she is post-menopausal
• GI workup showed gastritis on EGD which healed
  colonoscopy negative
• CBC Hgb 11.6 Hct 35.7 MCV 72 retic count 1.1
• Ferritin 7 vitamin B12 and folate normal

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Gastrointestinal sideropenia

• Case Laboratory data Response
• Case 1 Anti-gliadin abs () Responded to IV
• SA Anti-endomysial abs () iron dextran
  gluten-free diet
• Case 2 H. pylori antibody () Treated for H.
  pylori
• KK Responded to IV iron
• dextran Hgb 13.4
• Case 3 Responded to IV
• KH iron dextran
• Case 4 Bacterial overgrowth Treated with IV
  iron
• ES syndrome diagnosed dextran treated with
  rifaximin

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Celiac disease (Gluten-sensitive enteropathy)

• Common symptoms are diarrhea, abdominal pain and
  bloating
• Pathologic diagnosis by finding villous atrophy
  of small bowel mucosa
• Laboratory testing by IgA antibodies against
  gliadin, endomysium or tissue transglutaminase
  (sensitivity 90-95)

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Iron Deficiency in Celiac disease

• 484 adult patients with iron deficiency anemia
  were evaluated
• Compared with 498 non-anemic controls
• All screened for IgA anti-endomysial antibodies
• 17/484 anemic pts were IgA-EmA antibody positive
• 1/498 non-anemic pts. were IgA-EmA postiive
• All antibody positive patients were biopsy
  confirmed celiac disease
• 10/17 patients were pre-menopausal woman

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Prevalence of celiac disease in patients with
iron deficiency anemia

• Study No. pts. positive positive
• by biopsy by biopsy
• McIntyre 1993 114 -- 2.6
• Corazza 1995 200 8 5
• Unsworth 2000 483 6.6 4.6
• Haslam 2001 216 2.3 --
• Howard 2002 258 10.9 4.7
• Ransford 2002 484 3.5 2.3

Halfdanarson et al. Blood epub Sept 14, 2006
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Iron Deficiency in Celiac Disease

• 1026 cases of biopsy-proven celiac disease (644
  children 382 adults)
• 702 (68) women
• Extra-intestinal symptoms in adults
• Iron deficiency anemia 46Dermatitis
  herpetiformis
• Diabetes mellitus
• Short-stature in children

Am J Gastroenterology 1999 94691
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Treatment of Celiac disease with a Gluten-free
diet

• 190 patients with iron deficiency anemia
• 18 diagnosed with celiac disease by duodenal
  biopsy

Am J Gastroenterology (2001) 96133.
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Celiac disease and Iron Deficiency

• Celiac disease should be considered as a possible
  cause of anemia in patients with unexplained iron
  deficiency anemia including menstruating women
• Iron deficiency is common in celiac disease
• Celiac disease is frequently found in patients
  with iron deficiency
• Gluten-free diet and iron supplementation will
  replete the iron stores

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Helicobacter pylori infection

• H. pylori infection usually acquired by oral
  ingestion in childhood
• Prevalence 20-50 in industrialized countries
• Prevalence inversely related to socioeconomic
  conditions
• May be inadvertently cured by antibiotics
  treatment for other reasons
• Causes continuous gastric inflammation in all
  infected subjects

Dr. Barry Marshall, Nobel laureate
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Effects of H. pylori infection

• High acid output
• Antral gastritis
• Duodenal ulcer
• Low acid output
• Atrophic gastritis
• Gastric ulcer
• Gastric cancer
• MALT lymphoma

Rugae are almost completely lacking
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H. pylori infection and iron deficiency anemia

• Epidemiologic studies show H. pylori ()
  associated with decreased ferritin levels

Herschko, C Best Practice Clin Hemat 2005 18363
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H. pylori infection Mechanism of iron deficiency

• Occult GI bleeding
• Competition for dietary iron -
• would expect more patients to be
• iron deficient
• Effect on gastric secretion
• High intragastric pH
• Low gastric juice ascorbic acid

Possible cause of iron deficiency in H. pylori
infection mediated by achlorhydria
Annibale, B. et al. Gut 2003 52496
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Treatment of H. pylori infection Effect on pH
and ascorbic acid
Treatment of H. pylori depends on presence of
atrophy
Annibale, B. et al. Gut 2003 52496
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Atrophic Gastritis and Iron Deficiency Anemia

• Other causes of achlorhydria are associated with
  iron deficiency (pernicious anemia chronic
  alcohol use)

Gastrin for the diagnosis of atrophic
gastritis Diagnosis confirmed by
EGD Sensitivity 100 Specificity 74
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Anemic patients with atrophic body gastritis
Macrocytic anemia Microcytic anemia at
presentation at presentation Number of
pts. 44 36 Gender male/female
21/23 3/33 Age median (range) 65
(30-83) 45 (22-74) H. pylori positive
2 (4.5) 22 (61.1) Serum gastrin
pg/ml 491 (70-250) 236 (50-1400) Vitamin
B12 pg/ml 88 (20-320) 425 (165-840)
H. pylori seems to have a role in the development
of atrophic gastritis
Marigninani, et al. Am J. Gastro 1999 94766-772
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Bariatric surgery

• Laparoscopic banding Restricts caloric intake
• Roux-en-Y gastric bypass (RYGB) Malabsorptive
  and Restrictive
• Malabsorptive procedures more likely to result in
  nutritional deficiencies

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Bariatric surgery and iron deficiency

• Randomizes study of patient undegoing RYGB
  gastric bypass
• Ferrous sulfate 320 mg PO bid vs placebo

Brolin, et al. Arch Surg 1998 133740-744.
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Bacterial overgrowth syndrome

• Causes
• Alterations in intestinal anatomy (blind loop
  syndrome)
• Gastrointestinal motility disorder
• Achlorhydria
• Complications
• Abdominal pain, bloating diarrhea, weight loss,
  malabsorption
• No data on iron deficiency

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Possible evaluation of iron deficiency in the
absence of bleeding

• Endoscopic evaluation with small bowel biopsy for
  celiac disease
• Antibody studies for celiac disease
• H. pylori studies
• Anti-parietal cell and anti-intrinsic factor
  antibodies
• Gastrin level
• Studies for bacterial overgrowth

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Explaining unexplained iron deficiency anemia

• 150 consecutive patients with iron deficiency
  anemia referred to a hematology clinic
• No apparent GI disease or GI bleeding
• All patients anemic after oral iron supplements
• Screened for
• Celiac disease (anti-endomysial antibodies)
• Atrophic gastritis (gastrin, anti-parietal cell
  antibodies)
• H. pylori (IgG antibodies, urease breath test)

Hershko, C. et al. Haematologica 2005 90585-95
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Explaining unexplained iron deficiency anemia
Hershko, C. et al. Haematologica 2005 90585-95
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Explaining unexplained iron deficiency anemia
Response to oral iron therapy Refractory to
oral iron treatment 82 (55) Increased Hgb gt
1g/dl 48 (32) Intolerance to oral iron 4
(3) Non-compliance 10 (7) Prefer up front IV
iron therapy 3 (2) RBC transfusions 3 (2)
Hershko, C. et al. Haematologica 2005 90585-95
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Conclusions

• Evaluation of iron deficiency anemia should
  include evaluation for celiac disease, H. pylori
  and atrophic gastritis
• Refractoriness to oral iron therapy suggests
  abnormal iron absorption
• Males and post-menopausal females are most likely
  to have diagnostic studies