iron deficiency anemia a.h.emami md. associate professor of tums

Iron Deficiency AnemiaIron Deficiency Anemia

A.H.Emami MD.A.H.Emami MD.Associate professor of TUMSAssociate professor of TUMS

Learning ObjectivesLearning Objectives

Prevalence of IDAPrevalence of IDA Significance of Iron deficiencySignificance of Iron deficiency Iron homeostasis Iron homeostasis Stages of Iron deficiencyStages of Iron deficiency Symptoms & Signs of IDASymptoms & Signs of IDA Etiology of IDAEtiology of IDA Lab. Workup of IDALab. Workup of IDA Treatment of IDATreatment of IDA

IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

Data from the Third National Health Data from the Third National Health and Nutrition Examination Survey and Nutrition Examination Survey (NHANES III; 1988 to 1994) indicated (NHANES III; 1988 to 1994) indicated that iron deficiency anemia was that iron deficiency anemia was present in 1 to 2 percent of adultspresent in 1 to 2 percent of adults

It is estimated that 3% of men and It is estimated that 3% of men and 8% of women in the UK have iron 8% of women in the UK have iron deficiency anaemiadeficiency anaemia

Among low-income pregnant women Among low-income pregnant women in the US, the prevalence of anaemia in the US, the prevalence of anaemia in the first, second, and third in the first, second, and third trimesters was 9%, 14%, and 37%, trimesters was 9%, 14%, and 37%, respectivelyrespectively

IDA has been noted in up to 80% of IDA has been noted in up to 80% of Mexican pregnant women living in Mexican pregnant women living in the US and in >35% of children aged the US and in >35% of children aged under 2 years living in Argentinaunder 2 years living in Argentina

IDAIDA

The most common type of anemia all The most common type of anemia all over the worldover the world

Iron deficiency without anemia was Iron deficiency without anemia was more common, occurring in up to 11 more common, occurring in up to 11 percent of women (most often percent of women (most often premenopausal) and 4 percent of premenopausal) and 4 percent of men. men.

…………..found 36% of female and 6% of ..found 36% of female and 6% of male subjects to be iron deficient male subjects to be iron deficient without anemia.without anemia.

J Am Diet Assoc. 2005 Jun;105(6):975-8. 2005 Jun;105(6):975-8.

Prevalence of iron deficiency with and without anemia in recreationally active men and women.Prevalence of iron deficiency with and without anemia in recreationally active men and women. Sinclair LM, , Hinton PS..

Department of Nutritional Sciences, University of Missouri-Columbia, 65211, USADepartment of Nutritional Sciences, University of Missouri-Columbia, 65211, USA

In our research,85% of pregnant In our research,85% of pregnant women(on daily iron supplement) women(on daily iron supplement) were iron deficientwere iron deficient

Hemoglobin in circulating red cells and Hemoglobin in circulating red cells and developing erythroblasts — about 2.5 gdeveloping erythroblasts — about 2.5 g

Iron-containing proteins (eg, myoglobin, Iron-containing proteins (eg, myoglobin, cytochromes, catalase) — 400 mgcytochromes, catalase) — 400 mg

Plasma transferrin-bound iron — 3 to 7 mgPlasma transferrin-bound iron — 3 to 7 mg The remainder is storage iron in the form The remainder is storage iron in the form

of ferritin or hemosiderin.of ferritin or hemosiderin.

IRON BODY CONTENTIRON BODY CONTENT

Storage iron male: 800- 1000mgStorage iron male: 800- 1000mg

Female:300-500 mg Female:300-500 mg

The generally lower value for iron stores in adult women, for example, reflects the composite effect of menstrual losses (approximately 1 mg of iron loss per day), lower caloric intake, use of supplemental iron, and iron losses associated with pregnancy and lactation (about 1000 mg each for pregnancy, delivery, and nursing).

Storage iron in adult men has been estimated as being approximately 10 mg/kg, and is found mostly in liver, spleen, and bone marrow

For ferritin levels in the range from 20 to 300 ng/mL, there appears to be a direct quantitative relationship between the ferritin concentration and iron stores

Iron stores (mg)= (8 to 10) x ferritin (ng/mL)

Iron in daily DietIron in daily DietMale FemaleMale Female

15-20 mg 10-15 mg15-20 mg 10-15 mgDaily Iron NeedDaily Iron Need

Male FemaleMale Female1 mg 2 mg1 mg 2 mg

Iron BioavailabilityIron Bioavailability

Oxalates, Phytates,& Phosphetes Oxalates, Phytates,& Phosphetes

retard iron absorption retard iron absorption

Iron BioavailabilityIron Bioavailability

Ascorbate, lactate, pyruvate, Ascorbate, lactate, pyruvate, succinate, fructose,cystein and succinate, fructose,cystein and sorbitol increase iron absorptionsorbitol increase iron absorption

IRON ABSORPTION

Heme iron: Heme carrier Protein 1Heme iron: Heme carrier Protein 1

(HCP1)??(HCP1)??

.Ferric iron:.Ferric iron:

duodenal cytochrom b reductaseduodenal cytochrom b reductase

divalent metal transporter(DMT)1divalent metal transporter(DMT)1

FerroportinFerroportin

HephaestinHephaestin

HepcidinHepcidin

Causes of iron deficiency:Causes of iron deficiency:1-Increased demand for iron and / or hematopoiesis1-Increased demand for iron and / or hematopoiesis •• pregnancy pregnancy •• rapid growth in infancy or adolescence. rapid growth in infancy or adolescence. •• erythropoietin therapy erythropoietin therapy2- Increased iron loss2- Increased iron loss••chronic blood loss chronic blood loss ••MensesMenses••Acute blood lossAcute blood loss••Blood donationBlood donation••Phlebotomy as treatment for polycetemia veraPhlebotomy as treatment for polycetemia vera3- Decreased iron intake or absorption3- Decreased iron intake or absorption •• inadequate diet inadequate diet•• malabsorption from disease (sprue, crohn’s disease) malabsorption from disease (sprue, crohn’s disease)•• malabsorption from surgery (post-gastrectomy) malabsorption from surgery (post-gastrectomy) •• acute or chronic inflammation acute or chronic inflammation

Blood loss

Although reduced gastrointestinal absorption of iron and a diet deficient in iron can also cause iron deficiency, it is most reasonable to believe, as a first assumption, that iron deficiency reflects blood loss, in order to avoiding missing an occult malignancy or other bleeding intestinal lesion

In a study of 9024 participants in the NHANES I study, men and postmenopausal women with iron deficiency anemia had an increased risk of being diagnosed with a gastrointestinal malignancy within the subsequent two years (relative risk versus non-iron deficient controls 31, 95% CI 9-107)

In a report dealing with 148 consecutive patients with iron deficiency anemia, 18 patients (12 percent) were found to have a malignant tumor . Using multivariate analysis, the odds ratio for the presence of malignancy in a patient with a serum ferritin <10 microg/L and an LDH >250 U/L, when compared with patients having a ferritin >10 and an LDH <250, was 74 (95% CI 7-776).

Decreased iron absorption

Gastrointestinal malabsorption of iron is a relatively uncommon cause of iron deficiency, although it may be observed in certain diseases associated with generalized malabsorption or achlorhydria [4]. However, the use of proton pump inhibitors, which reduce gastric acid secretion, has not been associated with clinical iron deficiency.

These diagnoses (eg, atrophic gastritis, Helicobacter pylori gastritis, celiac disease) should be considered in patients with otherwise unexplained iron deficiency, especially when there is refractoriness to oral iron therapy

Celiac disease was the cause of iron deficiency in up to 10 percent of patients referred to a gastroenterologist in one report , and in up to 8.5 percent of patients with iron deficiency anemia unresponsive to oral iron therapy in another study

Clinical ManifestationsClinical Manifestations

Clinical manifestationsClinical manifestations

The usual presenting symptoms in The usual presenting symptoms in adults, as seen in current practice, adults, as seen in current practice, are primarily due to anemia and are primarily due to anemia and include weakness, headache, include weakness, headache, irritability and varying degrees of irritability and varying degrees of fatigue and exercise intolerance.fatigue and exercise intolerance.


Most frequently,symptoms are Most frequently,symptoms are misinterpreted as depression. misinterpreted as depression.


However, many patients are However, many patients are asymptomatic and present only with asymptomatic and present only with anemia. anemia.

PICAPICA

PICAPICA

refers to a perverted appetite for refers to a perverted appetite for substances not fit as food :substances not fit as food :

GeophaiaGeophaia PagophagiaPagophagia AmylophagiaAmylophagia ……..(carrot,tea,dried lemon ,cube ..(carrot,tea,dried lemon ,cube

sugar)sugar)

PICAPICA

Pagophagia, or pica for ice, is considered quite specific for the iron deficiency state

PICAPICA

It may be present in patients who are not anemic and responds rapidly to treatment with iron, often before any increase is noted in the hemoglobin concentration. In one study of 55 unselected patients with iron deficiency anemia secondary to gastrointestinal blood loss, pica was present in 32 and pagophagia in 28

Neuromuscular symptomsNeuromuscular symptoms

Impaired auditory developmentImpaired auditory development Impaired cognitive developmentImpaired cognitive development Involuntary movements Involuntary movements (during sleep)(during sleep)

Restless leg syndromeRestless leg syndrome

The sensitivity and specificity for The sensitivity and specificity for pallor in the palms, nail beds, face, pallor in the palms, nail beds, face, or conjunctivae as a predictor for or conjunctivae as a predictor for anemia varies from 19 to 70 percent anemia varies from 19 to 70 percent and 70 to 100 percent, respectivelyand 70 to 100 percent, respectively

Lab. FeaturesLab. Features

Initial testing of the anemic patient Initial testing of the anemic patient should include a "complete" blood should include a "complete" blood count (CBC). This routinely includes count (CBC). This routinely includes HGB, HCT, RBC count, RBC indices, HGB, HCT, RBC count, RBC indices, and white blood cell (WBC) count.and white blood cell (WBC) count.


Three RBC indices are usually Three RBC indices are usually measured by automated blood measured by automated blood counters: mean corpuscular volume counters: mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular (MCH), and mean corpuscular hemoglobin concentration (MCHC) hemoglobin concentration (MCHC)

The values for MCH and MCHC The values for MCH and MCHC generally parallel the information generally parallel the information obtained from the MCV (ie, larger or obtained from the MCV (ie, larger or smaller RBCs tend to have higher or smaller RBCs tend to have higher or lower values for MCH, respectively). lower values for MCH, respectively).

The normal range for MCV is from 80 The normal range for MCV is from 80 to 100 femtoliters (fL).to 100 femtoliters (fL).


Accordingly, the blood smear should Accordingly, the blood smear should always be reviewed by an always be reviewed by an experienced examiner, since many experienced examiner, since many important changes may be missed by important changes may be missed by the inexperienced observer and may the inexperienced observer and may not be detected by automated blood not be detected by automated blood counters counters

IDAIDA

More complete evaluation for iron More complete evaluation for iron deficiency is indicated when the deficiency is indicated when the history (menometrorrhagia, history (menometrorrhagia, symptoms of peptic ulcer disease) symptoms of peptic ulcer disease) and preliminary laboratory data (low and preliminary laboratory data (low MCV, low MCH, high RDW, increased MCV, low MCH, high RDW, increased platelet count) support this diagnosisplatelet count) support this diagnosis

In this setting, the plasma levels of In this setting, the plasma levels of iron, iron binding capacity iron, iron binding capacity (transferrin), transferrin saturation, (transferrin), transferrin saturation, or ferritin should be measuredor ferritin should be measured

Laboratory iron studies:Laboratory iron studies:

1- Serum iron (50-150mg/dl)1- Serum iron (50-150mg/dl)1-Total iron-binding capacity TIBC (300-360 mg/dl)1-Total iron-binding capacity TIBC (300-360 mg/dl)1-Transferrin saturation (serum iron × 100 ÷ TIBC)1-Transferrin saturation (serum iron × 100 ÷ TIBC)2- Serum ferritin Serum ferritin3- Marrow iron stores3- Marrow iron stores4- Red cell protoporphyrin levels4- Red cell protoporphyrin levels5- Serum level of transferrin receptor5- Serum level of transferrin receptor

IDAIDA

Stages of iron deficiency :Stages of iron deficiency :

- Iron store depletion- Iron store depletion- Iron – deficient erythropoiesis- Iron – deficient erythropoiesis- Iron – deficiency Anemia- Iron – deficiency Anemia

Differential diagnosis Differential diagnosis

- Thalassemias- Thalassemias- Chronic inflammatory - Chronic inflammatory diseasedisease- Myelodysplastic syndromes- Myelodysplastic syndromes

Minor thalasemia:Minor thalasemia:

consider mcvconsider mcv

RBC countRBC count

(>5.000.000 vs.<5.000.000)(>5.000.000 vs.<5.000.000)

Anemia of chronic disorder:Anemia of chronic disorder:

25% of patients with ACD present 25% of patients with ACD present with hypochromic microcytic anemiawith hypochromic microcytic anemia

Hypothyroidism:Hypothyroidism:

In women it presents with severe iron In women it presents with severe iron deficiency anemia(due to increased deficiency anemia(due to increased mens. Loss) which is partially mens. Loss) which is partially responsive to iron replacement.responsive to iron replacement.

Ferritin is an acute phase reactant, Ferritin is an acute phase reactant, with plasma levels increasing in liver with plasma levels increasing in liver disease, infection, inflammation, and disease, infection, inflammation, and malignancy.malignancy.

The effect of inflammation is to The effect of inflammation is to elevate serum ferritin approximately elevate serum ferritin approximately threefold .threefold .

A useful rule-of-thumb in such A useful rule-of-thumb in such patients is to divide the patient's patients is to divide the patient's serum ferritin concentration by threeserum ferritin concentration by three

MDS-sideroblastic anemiaMDS-sideroblastic anemia

Consider morphologic ghangesConsider morphologic ghanges

Delineation of causeDelineation of cause

Once the diagnosis of anemia due to Once the diagnosis of anemia due to iron deficiency is established, iron deficiency is established, attempts must be made to identify attempts must be made to identify the cause.the cause.


The search starts with the history, The search starts with the history, which in women is directed to which in women is directed to menses, pregnancy, delivery, menses, pregnancy, delivery, lactation, and, in both men and lactation, and, in both men and women, to sources of overt or occult women, to sources of overt or occult blood loss.blood loss.


The standard test for detecting The standard test for detecting occult gastrointestinal bleeding has occult gastrointestinal bleeding has been the Hemoccult II card, which been the Hemoccult II card, which has a low sensitivity for detecting has a low sensitivity for detecting colon cancer.colon cancer.


Subsequent evaluation is determined Subsequent evaluation is determined by the initial findings. The initial test by the initial findings. The initial test that is performed (colonoscopy or that is performed (colonoscopy or endoscopic examination of the upper endoscopic examination of the upper gastrointestinal tract) can be chosen gastrointestinal tract) can be chosen based upon the findings on the based upon the findings on the history.history.


One report, for example, One report, for example, prospectively evaluated 100 patients prospectively evaluated 100 patients with presumed occult fecal blood loss with presumed occult fecal blood loss with colonoscopy, with colonoscopy, esophagogastroduodenoscopy, and, esophagogastroduodenoscopy, and, if these tests are negative, if these tests are negative, radiographic examination of the radiographic examination of the small intestine small intestine


. A source of bleeding was identified . A source of bleeding was identified in 62 patients (62 percent). A lesion in 62 patients (62 percent). A lesion was seen on colonoscopy in 25, was seen on colonoscopy in 25, endoscopic examination of the upper endoscopic examination of the upper gastrointestinal tract in 36, and both gastrointestinal tract in 36, and both in one.in one.


Peptic ulcer disease (duodenal, Peptic ulcer disease (duodenal, gastric, or anastomotic) was the gastric, or anastomotic) was the primary abnormality found in the primary abnormality found in the upper gastrointestinal tract.upper gastrointestinal tract.


Cancer, detected in 11 patients, was Cancer, detected in 11 patients, was the most common finding on the most common finding on colonoscopy.colonoscopy.


No abnormalities were seen on No abnormalities were seen on radiographic studies of the small radiographic studies of the small bowel in 38 patients.bowel in 38 patients.


Intravascular hemolysis with iron Intravascular hemolysis with iron losses through the urine losses through the urine

Pulmonary hemosiderosisPulmonary hemosiderosis Gastrointestinal iron malabsorption Gastrointestinal iron malabsorption

(often with concomitant bleeding)(often with concomitant bleeding) Response to therapy with Response to therapy with

erythropoietin, in which there is a erythropoietin, in which there is a demand for iron to allow for demand for iron to allow for increased red cell productionincreased red cell production

If there is any other cytopenia,always If there is any other cytopenia,always consider MDS& PNHconsider MDS& PNH

Treatment of IDATreatment of IDA

- Treatment of the causes- Treatment of the causes- - Red cell transfusionRed cell transfusion- Oral iron therapy:- Oral iron therapy: tablet-Elixir tablet-Elixir


There are a few simple principles There are a few simple principles governing the use of oral iron:governing the use of oral iron:

1-Iron should be given two hours 1-Iron should be given two hours before, or four hours after, ingestion before, or four hours after, ingestion of antacids. of antacids.


2-Iron is absorbed best from the 2-Iron is absorbed best from the duodenum and proximal jejunum. duodenum and proximal jejunum. Therefore, the more expensive Therefore, the more expensive enteric coated or sustained release enteric coated or sustained release capsules, which release iron further capsules, which release iron further down in the GI tract, are down in the GI tract, are counterproductive. counterproductive.


3-Iron salts should not be given with 3-Iron salts should not be given with food because the phosphates, food because the phosphates, phytates, and tannates in food bind phytates, and tannates in food bind the iron and impair its absorption the iron and impair its absorption


4-The iron preparation used should be 4-The iron preparation used should be based upon cost and effectiveness based upon cost and effectiveness with minimal side effects. The with minimal side effects. The cheapest preparation is ferrous cheapest preparation is ferrous sulfate; each tablet contains 325 mg sulfate; each tablet contains 325 mg of iron salts, of which 65 mg is of iron salts, of which 65 mg is elemental ironelemental iron

Response To TreatmentResponse To Treatment

Check baseline retic. CountCheck baseline retic. Count Start of reticulocytosis:d 3-4Start of reticulocytosis:d 3-4 Max. reticulocytosis:d 7-10Max. reticulocytosis:d 7-10 Onset of Hb. Rise:d 14Onset of Hb. Rise:d 14 Hb.rise:1 gr/dl/weekHb.rise:1 gr/dl/week

Failure to respond to oral iron Failure to respond to oral iron therapytherapy

*Incorrect diagnosis *Incorrect diagnosis

* Presence of a coexisting disease * Presence of a coexisting disease interfering with response interfering with response

**Patient is not taking the medication **Patient is not taking the medication *Medication is not being absorbed for *Medication is not being absorbed for physical reasons physical reasons

**Iron (blood) loss or need is in excess of the **Iron (blood) loss or need is in excess of the amount ingested amount ingested

* The patient has malabsorption for iron* The patient has malabsorption for iron

- Parental iron therapy- Parental iron therapy IM - IV IM - IVBody weight (Lbs)*(15 or13 - Body weight (Lbs)*(15 or13 - patientpatient’’s Hb g/dl)s Hb g/dl)+ 500 or 1000 = Total dose (mg)+ 500 or 1000 = Total dose (mg)

There is disagreement as to how There is disagreement as to how long to continue iron therapylong to continue iron therapy

PREVENTION PREVENTION

CDC guidelines:CDC guidelines:

For girls ages 12 to 18 and For girls ages 12 to 18 and nonpregnant women of childbearing nonpregnant women of childbearing age: screening for anemia every 5 to age: screening for anemia every 5 to 10 years during a routine 10 years during a routine examination examination

women with risk factors for iron women with risk factors for iron deficiency :Annual screeningdeficiency :Annual screening

Pregnant women should begin taking Pregnant women should begin taking low dose (30 mg/day) oral iron at the low dose (30 mg/day) oral iron at the first prenatal visit as primary first prenatal visit as primary prevention of iron deficiency prevention of iron deficiency

Women should also be screened for Women should also be screened for iron deficiency at the first prenatal iron deficiency at the first prenatal visit visit

postmenopausal women do not need postmenopausal women do not need routine screening for iron deficiency. routine screening for iron deficiency.

iron deficiency anemia a.h.emami md. associate professor of tums

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