Iron Iron Deficiency Deficiency

AnemiaAnemia（缺铁性贫血）（缺铁性贫血）

瑞金医院血液科瑞金医院血液科

Normal iron Normal iron physiologyphysiology

Question ?Question ?

• Total body iron?- 4 g- 40 g- 400 g

Important Fe-containing Important Fe-containing compounds in the humancompounds in the human

Total body iron

Operational iron

Hemoglobin （血红蛋白） 2.6 g 67 %

Myoglobin （肌红蛋白） 0.13 g 15 %

Transferrin （转铁蛋白） 3 mg 0.1 %

other heme-containing enzymes:cytochromes, peroxidase, catalase

Storage iron Ferritin and hemosiderin（铁蛋白、含铁血黄素）

0.52 g 13 %0.48 g 12 %

About 4 g

The body’s iron economyThe body’s iron economy

DefinitionDefinition

HistoryHistory

• Anemia:male<120g/l,female<110g/l• Caused by lack of iron• Medieval times• “chlorosis”, a term derived from Gree

k word meaning “green”• “green sickness” greenish pallor as a prominent manifest

ation

1 ） Stage 1: Iron depletion ( 铁耗减阶段） storage iron is decreased or absent serum iron concentration and blood hemoglobin levels are normal

2 ） Stage 2: Iron deficient erythropoiesis ( 红细胞内铁缺乏阶段） storage iron is decreased or absent low serum iron concentration and transferrin saturation, without frank anemia

3 ） Stage 3: Iron deficiency anemia （缺铁性贫血阶段） storage iron is decreased or absent low serum iron concentration and transferrin saturation low hemoglobin level and hematocrit value hypochromic microcytic erythrocytes

PrevalencePrevalence

The incidence of IDA in USAThe incidence of IDA in USA

• < 1% adult men younger than 50 years of age

• 2-4% adult men older than 50 years of age

• 9-11% in menstruating women• 1-7% postmenopausal women• Particularly common in infants (6-20

months) and pregnant women

The incidence of IDA in ShanghaiThe incidence of IDA in Shanghai

Age Iron deficiency（ %

）

Iron deficiency anemia（ %）

6个月 ~2岁的婴幼儿

75.0~82.5 33.8~45.7

育龄妇女 43.32 11.39

妊娠 3个月以上妇女

66.27 19.28

10 岁 ~17 岁青少年 13.17 9.84

EtiologyEtiology andand PathogenesisPathogenesis

• Insufficient iron in the diet and periods of rapid growth

• Poor absorption of iron by the body • Ongoing blood loss, most commonly

from menstruation or from gradual blood loss in the intestinal tract

EtiologyEtiology

Insufficient iron in the diet and Insufficient iron in the diet and periods of rapid growthperiods of rapid growth

• Infants, children, and adolescents in rapid growth phases Infants - cow’s milk, prematurity and low birth weight1-3 years old children - cow’s milk and low iron foodadolescents - more growth occurs, menstrual blood loss

• Pregnant or lactating women having an increased requirement for ironFetus for erythropoiesis, blood loss at delivery, and lactation - 900mgiron-deficiency mothers are likely to have babies with low iron reserves

MalabsorptionMalabsorption Atrophic gastritis （萎缩性胃炎） Achlorhydria （胃酸缺乏） Drugs that increase gastric PH : antaacid Gastric surgery : gastrectomy

（胃切除术） Duodenal bypass

Blood lossBlood loss• In most adult cases, iron deficiency results from blood loss. Clinically sig

nificant blood loss can be occult, meaning the source of the blood loss is unknown.

A careful history is useful in determining the source of blood lossGastrointestinal Upper Nosebleeds (including telangiectasia ）鼻出血 Varices 血管曲张 Gastritis 胃炎 Ulcer 溃疡 Lower Meckel’s diverticulum (Children) 憩室 Milk-induced enteropathy (Children) 肠病 Helminthiasis 肠虫病 Tumor or polyps 肿瘤或息肉 Ulcerative colitis 溃疡性结肠炎 Arteriovenous malformation 动静脉畸形 Diverticuli 憩室 Hemorrhoids 痔疮 Vaginal Increased menstrual flow 月经过多 Tumor 肿瘤 Urinary Tumor 肿瘤 Chronic infection 慢性感染 Pulmonary Pulmonary hemosiderosis 肺含铁血黄素沉着症 Tuberculosis 结核 Bronchiectasis 支气管扩张

PathogenesisPathogenesis

• Not enough iron

• Limited hemoglobin production

• Decreased red blood cells/Fe-enzymes

• Insufficient oxygen

• Cells and tissues hypoxia/biologic function

Clinical Clinical ManifestationManifestation

• Symptoms of primary disease

• Symptoms of anemia

• Symptoms of iron deficiency in the tissues

Symptoms caused by anemiaSymptoms caused by anemia

• Fatigue and weakness • Dizziness or a feeling of being

lightheaded • Palpitations and breathlessness• Pale skin and mucous membranes• Irritability • Decreased appetite

Neuromuscular systemNeuromuscular system

• Neuralgia pains• Numbness and tinglingChildren• Developmental delay• Ischemic stroke• Increased intracranial pressure• Papilledema• Clinical picture of pseudotumor cerebri

Epithelial tissuesEpithelial tissues

• Nails - koilonychia : “spoon-shaped” nails

• Tongue and mouth- atrophy of lingual papillae- ulcerations or fissures at the corners of the mouth

• Stomach- Gastritis

Koilonychia Koilonychia （匙状指）（匙状指）

Koilonychia, or spooning of the fingernails, is another abnormality that may be seen in severe, long-standing iron deficiency. Normally, the cells of the nail bed proliferate rapidly, but their growth is impaired by iron deficiency, producing thin nails that are soft and fragile. The abnormalities are now rarely seen. But they are obvious clinical signs that aid in diagnosis when present.

Pica patient:

Pica, the craving to eat unusual substance such as dirt, clay, ice, laundry starch, salt, cardboard, or hair, is a classic manifestation of iron deficiency and is usually cured promptly by iron therapy.

Pica Pica （异食癖）（异食癖）

Glossitis （ smooth, red tongue)

stomatitis

angular cheilitis

Laboratory Laboratory featuresfeatures

Erythrocytes and bone marrowErythrocytes and bone marrow

Blood smear

Hemoglobin concentration

MCV ( 平均红细胞体积 )<80fl

MCH ( 平均红细胞血红蛋白量 )<27pg

MCHC ( 平均红细胞血红蛋白浓度 )<32%

Bone marrow smear

Stainable iron in the bone marrowStainable iron in the bone marrow

Prussian blue reaction

Iron metabolismIron metabolism

• Serum iron concentration - normal : 9.0 - 30.0 mol/L - IDA : < 9.0 mol/L

Serum iron directly measures the amount of iron in the blood, but may not accurately reflect how much iron is concentrated in the body's cells

• Iron binding capacity- normal : 54.0 - 77.0 mol/L - IDA : >77.0 mol/L

a measure of the amount of transferrin in blood

Iron metabolismIron metabolism

• Transferrin saturationNormal : 15.0 - 50.0%IDA : <15.0%

The assays used to measure with serum iron and Iron binding capacity together, to differentiate iron deficiency from other diseases. In IDA, iron binding capacity is often increased, while transferrin saturation is often less than 15%.

Iron metabolismIron metabolism• Soluble transferrin receptor(sTfR) > 8mg/L sTfR is a normal proteolytic cleavage product of transferrin recep

tor derived from erythroid precursor cells. Because it is not elevated in the anemia of chronic disease, it can be particularly useful in distinguishing that condition from iron deficiency.

• Serum ferritin concentration <12 g/L Serum ferritin reflects is the single best serum measure of storage

iron and is one of the earliest indicators of depleted iron levels.

• FEP ( 游离原卟啉 ) >0.9 mol/L Assay of free erythrocyte protoporphyrin is most commonly perfo

rmed in children to distinguish various disorders that may be confused with iron deficiency. Measurement of free erythrocyte protoporphyrin can help distinguish between iron deficiency anemia, in which the level is high, and thalassemia, in which the level is low.

• FEP/Hb>4.5 μg/gHb • ZPP ( 锌原卟啉） > 0.96 mol/L ( 全血） When iron is not available for incorporation into protoporphyrin,

the zinc chelate of protoporphyrin forms readily. Patients with elevated ZPP should undergo further testing to differentiating iron deficiency from some other causes of anemia.

DiagnosisDiagnosis

• ID 血清铁蛋白 <12 μg/L 骨髓可染铁消失，铁粒幼细胞小于 15 ％ 血红蛋白和血清铁指标正常

• IDE ID 的 ＋ 转铁蛋白饱和度 <15% FEP/Hb >4.5 μg/gHb 血红蛋白尚正常

• IDA ID 的 ＋ ＋ 小细胞低色素性贫血：男性 Hb<120g/L ，女性 Hb<110g/L, 孕妇

Hb<100g/L; MCV<80fl, MCH<27pg,MCHC<32%• 病因诊断

Causes for IDACauses for IDA• In infants and young children, inadequate nutrition or e

xcessive cow’s milk consumption probably accounts for most cases of iron deficiency. Blood loss should also be assessed.

• In iron-deficient adults, the history of surgeries or intravascular hemolysis should be noted.

• In women of childbearing age, menstrual loss is a primary consideration

• In male and female patients of other ages, gastrointestinal blood loss should be considered if no other source is apparent.

Differential Differential diagnosisdiagnosis

Diseases that can complicate or be confused Diseases that can complicate or be confused with iron deficiencywith iron deficiency

Disease Manifestation

Anemia of chronic disease (chronic infections and inflammation, malignancy)

Not responsive to iron therapy; associated disease may also cause blood loss and coexistent iron deficiency. Measurement of stainable iron may help

β-thalassemia May have normalization of hemoglobin A2 levels if iron deficiency coexists. After iron stores have been replenished, an abnormalities hemoglobin electrophoresis will be shown(including elevated hemoglobin A2 level)

α-thalassemia Low MCV, even with normal hemoglobin; hemoglobin electrophoresis not helpful

Sideroblastic anemia Hypochromic blood picture, but bone marrow examination confirms diagnosis

Folate or cobalamin deficiency

MCV is normal when coexistent with iron deficiency. Serum folate concentration and cobalamin concentration will help diagnosis

Thalassemia minorThalassemia minor• Southeast Asia• Hypochromia, microcytosis• Elevated erythrocyte count• Very low MCV 60-70 fl• Normal or increased iron concentration• Increased proportions of hemoglobin A2 or F,

or by the presence of electrophoresis of hemoglobin H or Lepore

Anemia of chronic inflammatory Anemia of chronic inflammatory disease and malignancydisease and malignancy

• Normochromia and normocytic, but 20 -30% hypochromic, microcytic

• Decreased serum iron concentration• Increased transferrin saturation• Increased serum ferritin • Normal or increased stainable iron in bone ma

rrow

Anemia of hemolytic diseaseAnemia of hemolytic disease

• Poikilocytosis, polychromatophilia, and other morphologic features characteristic of hemolysis

• Marked reticulocytosis• Normal or increased serum iron concentration

TherapyTherapy

Principle:

• Iron replacement therapy • To treat the causes of iron deficiency

Dietary therapyDietary therapy

• Neither meat nor any other dietary article contains enough iron to be useful therapeutically

• 3-oz steak provides only 3 mg ironprovision of sufficient

iron for treatment?

4540 g of steak

Oral iron therapyOral iron therapy

制剂 规格 含铁量（ %）硫酸亚铁 0.3 g/ 片 20

富马酸亚铁 0.2 g/ 片 33

葡萄糖酸亚铁 0.3 g/ 片 12

枸橼酸铁胺 10 % 溶液 20

右旋糖酐铁 25 mg/ 片 35

琥珀酸亚铁（速力菲）

0.1 g/ 片 35

多糖铁复合物（力蜚能）

150 mg/ 胶囊 46

维铁缓释片（福乃得）

1 片 硫酸亚铁 525mgVitc 500mg

Oral iron therapyOral iron therapy• Effective, safe, and inexpensive• Enhanced by the presence of orange

juice, meat, poultry and fish• Decreased by cereals, tea and milk• Side effect :

- gastrointestinal irritation heartburn, nausea, diarrhea

taken immediately after or even with a meal

Response to oral iron therapyResponse to oral iron therapy• Varies according to factors such as patient complianc

e, efficiency of absorption, and rate of continued iron loss.

• 7 to 10 days : reticulocyte count increases • after 2-3 weeks : hemoglobin level increases • 2 months : hemoglobin level reach the normal range• Iron replacement should be continued until body iron

stores have been replenished, usually requiring an additional 4 to 6 months of therapy after the hemoglobin level has been corrected

Failure of oral iron therapyFailure of oral iron therapy• Blood loss greater than hemoglobin regeneration• Incorrect diagnosis (e.g., thalassemia trait)• Superimposed infection, inflammation, malignancy, o

r uremia• Noncompliance• Lead poisoning• Defective gastrointestinal iron absorption• Concomitant folate or cobalamin deficiency• Copper deficiency• Renal failure resulting in erythropoietin deficiency• Rare, inherited defects of iron transport or use

• Severe iron deficiency anemia• Unable to tolerate oral iron therapy• Iron (blood) loss too rapid for oral intake to com

pensate for the loss(hereditary hemorrhagic telangiectasia)

• Disorders of gastrointestinal tract(ulcerative colitis)

• Unable to maintain iron balance on treatment with hemodialysis

• Functional iron deficiency because of concurrent treatment with erythropoietin

Indications for intravenous Iron DextrIndications for intravenous Iron Dextran Therapyan Therapy

Iron Dextran therapyIron Dextran therapy• 右旋糖酐铁 (iron-dextran complex) 是最

常用的注射铁剂，首次给药须用 0.5ml 作为试验剂量， 1 小时后无过敏反应可给足量治疗，第一天给 50mg ，以后每日或隔日给 100mg ，直至总需量

• 注射用铁的总需量按公式计算：（需达到的血红蛋白浓度－患者的血红蛋白

浓度） X 0.33 X 患者体重（ kg ）

Side effects of Side effects of Iron Dextran therapyIron Dextran therapy

• Pain in the vein injected, flushing• Metalic taste• Hypotension, headache, malaise, and na

usea• Lymphadenopathy, myalgia, arthralgia,

and fever• Anaphylactic reaction

PrognosisPrognosis

• Rarely, iron-deficiency anemia is so severe that hospitalization may be necessary. A blood transfusion may be required to treat severe, life-threatening anemia.

Key pointsKey points• Three stages of iron deficiency

anemia

• Diagnosis

• Iron therapy