Iron-deficiency Iron-deficiency anemia anemia

By: Dr. Sabir M. AmeenBy: Dr. Sabir M. Ameen

iron metabolismiron metabolism

Daily diet contain 15-20 mg of ironDaily diet contain 15-20 mg of iron Only 10% of this is absorbedOnly 10% of this is absorbed Absorption increases ( 20-30%) in iron-Absorption increases ( 20-30%) in iron-

deficiency and pregnancydeficiency and pregnancy Haem iron ( in meat) is better absorbed than Haem iron ( in meat) is better absorbed than

non-haem iron ( in cereals, milk)non-haem iron ( in cereals, milk) Absorption takes place in duodenum and Absorption takes place in duodenum and

jejunumjejunum Absorption is favored by acidity of stomach Absorption is favored by acidity of stomach

keeping iron in ferrous rather than ferric formkeeping iron in ferrous rather than ferric form

Iron storesIron stores

2/3 of total body iron is in circulation 2/3 of total body iron is in circulation as Hb (2500-3000 mg)as Hb (2500-3000 mg)

Iron is stored in reticuloendothelial Iron is stored in reticuloendothelial cells, hepatocytes, and skeletal cells, hepatocytes, and skeletal muscles( 500-1500 mg)muscles( 500-1500 mg)

2/3 of stored iron is in form of 2/3 of stored iron is in form of ferritinferritin and 1/3 in form of and 1/3 in form of hemosiderinhemosiderin

About 4 mg is found in plasma bound About 4 mg is found in plasma bound to to transferrintransferrin

requiermentsrequierments

Each day 0.5-1.0 mg of iron is lost in Each day 0.5-1.0 mg of iron is lost in feces, urine, and sweatfeces, urine, and sweat

Menstruating women lose 40 ml of Menstruating women lose 40 ml of blood per month ( 0.7 mg of blood per month ( 0.7 mg of iron/day)iron/day)

Blood loss in excess of 100ml Blood loss in excess of 100ml through menstruation will result in through menstruation will result in iron-deficiencyiron-deficiency

causescauses

Blood lossBlood loss Increased demands ( growth and Increased demands ( growth and

pregnancy)pregnancy) Decreased absorption ( e.g Decreased absorption ( e.g

postgastrectomy)postgastrectomy) Poor intakePoor intake

Most common is blood loss usually from Most common is blood loss usually from uterus or GITuterus or GIT

Iron-deficiency affects more than ¼ of world’s Iron-deficiency affects more than ¼ of world’s populationpopulation

Clinical featuresClinical features

Symptoms ( non-specific):Symptoms ( non-specific):

Fatigue, headaches, faintness, Fatigue, headaches, faintness, breathlessness, angina of effort, breathlessness, angina of effort, intermittent claudication, palpitationsintermittent claudication, palpitations

Signs: pallor, tachycardia, systolic flow Signs: pallor, tachycardia, systolic flow murmur, heart failure, murmur, heart failure,

Specific signs: brittle nails, koilonychia, Specific signs: brittle nails, koilonychia, atrophy of papillae of tongue, angular atrophy of papillae of tongue, angular stomatitis, brittle hair, dysphagia( Plummer-stomatitis, brittle hair, dysphagia( Plummer-Vinson or Paterson-Kelly syndrome)Vinson or Paterson-Kelly syndrome)

KoilonychiaKoilonychia

Koilonychia - spoon shaped nail

Angular stomatitisglossitisglossitis

Nutritional deficiency anemiaNutritional deficiency anemia

investigationsinvestigations Blood count and film:Blood count and film:RBCs are microcytic ( MCV < 80 fl) and hypochromic RBCs are microcytic ( MCV < 80 fl) and hypochromic

( MCH < 27pg)( MCH < 27pg)There is There is poikilocytosispoikilocytosis ( variation in shape) and ( variation in shape) and

anisocytosisanisocytosis (variation in size) (variation in size)Target cells are seenTarget cells are seen Low serum ferritinLow serum ferritin Low serum iron and high total iron binding capacity Low serum iron and high total iron binding capacity

( TIBC)( TIBC) Transferrin saturation ( serum iron divided by TIBC ) is Transferrin saturation ( serum iron divided by TIBC ) is

< 19%< 19% BM: erythroid hyperplasia with ragged BM: erythroid hyperplasia with ragged

normoblasts ,but BM examination is not essential for normoblasts ,but BM examination is not essential for diagnosisdiagnosis

Differential diagnosis of Differential diagnosis of microcytic and microcytic and

hypochromic anemiahypochromic anemia Thalassemia (Thalassemia (αα or or ββ): s. Fe is normal, ): s. Fe is normal,

and TIBC normal, also ferritin is and TIBC normal, also ferritin is normalnormal

Sideroblastic anemia: s. Fe is raised, Sideroblastic anemia: s. Fe is raised, TIBC is normal, serum ferritin raisedTIBC is normal, serum ferritin raised

Anemia of chronic disease: s. Fe is Anemia of chronic disease: s. Fe is reduced, TIBC is reduced, and reduced, TIBC is reduced, and serum ferritin normal or raisedserum ferritin normal or raised

treatmenttreatment

First find and treat the causeFirst find and treat the cause Then give iron to correct anemiaThen give iron to correct anemia Finally give iron to replace iron storesFinally give iron to replace iron stores Iron is best given orally as ferrous Iron is best given orally as ferrous

sulphate on empty stomach, if side sulphate on empty stomach, if side effects develop such as nausea, diarrhea effects develop such as nausea, diarrhea or constipation, tablets given with food or constipation, tablets given with food or reducing dose with another or reducing dose with another preparation as ferrous gluconatepreparation as ferrous gluconate

TreatmentTreatment

ORALORAL 200 mg of iron daily 1 hour before meal 200 mg of iron daily 1 hour before meal

(e.g. 100 mg twice daily)(e.g. 100 mg twice daily) How long?How long?

14 days + (H14 days + (Hbb required level – H required level – Hbb current current level) x 4 level) x 4

half of the dose 6 – 9 months to restore half of the dose 6 – 9 months to restore iron reserveiron reserve

Absorption Absorption is enhanced: vitis enhanced: vit C, meat, orange juice, fishC, meat, orange juice, fish is inhibited: cereals, tea, milkis inhibited: cereals, tea, milk

TreatmentTreatment

PARENTERAL IRON SUBSTITUTIONPARENTERAL IRON SUBSTITUTION Bad oral iron tolerance (nausea, diarrhoea)Bad oral iron tolerance (nausea, diarrhoea)

Necessity of quick management (CHD, CHF)Necessity of quick management (CHD, CHF) 50 - 100 mg daily50 - 100 mg daily I.v only in hospital (risk of anaphI.v only in hospital (risk of anaphyylactic lactic

shock)shock) I.m in outpatient department I.m in outpatient department Total dose by iv infusion:Total dose by iv infusion: iron to be injected (mg) = (15iron to be injected (mg) = (15 - Hb g ) x body - Hb g ) x body

weight (kg) x 3weight (kg) x 3

Failure of response to Failure of response to oral ironoral iron

Lack of complianceLack of compliance Continuing hemorrhageContinuing hemorrhage Severe malabsorptionSevere malabsorption Another cause for the anemiaAnother cause for the anemia

These possibilities should be These possibilities should be considered before using parenteral considered before using parenteral ironiron

Normal Peripheral SmearNormal Peripheral Smear

Iron Deficiency AnemiaIron Deficiency Anemia

Anemia of chronic Anemia of chronic diseasedisease (ACD) - definition(ACD) - definition

ACD is a common type of anemia ACD is a common type of anemia that occurs in patients with infectious, that occurs in patients with infectious, inflammatory, or neoplastic diseases inflammatory, or neoplastic diseases that persist for more than 1 or 2 that persist for more than 1 or 2 months.months.

It does not include anemias caused It does not include anemias caused by marrow replacement, blood loss, by marrow replacement, blood loss, hemolysis, renal insufficiency, hepatic hemolysis, renal insufficiency, hepatic disease, or endocrinopathy, even when disease, or endocrinopathy, even when these disthese disoorders are chronic. rders are chronic.

Anemia of chronic disease Anemia of chronic disease (ACD) -epidemiology(ACD) -epidemiology

The ACD is extremely commonThe ACD is extremely common ACD is more common thaACD is more common thann any anemia syndrome any anemia syndrome

other than blood loss with consequent iron deficiencyother than blood loss with consequent iron deficiency ACD is the most common cause of anemia in ACD is the most common cause of anemia in

hospitalized patientshospitalized patients After patients with bleeding, hemolysis, or known After patients with bleeding, hemolysis, or known

hematologic malignancy were excluded, 52% of hematologic malignancy were excluded, 52% of anemic patients met laboratory criteria for the anemic patients met laboratory criteria for the anemia of chronic disordersanemia of chronic disorders

ACD is observed in 27% of outpatients with ACD is observed in 27% of outpatients with rheumatoid arthritis and in 58% of new admissions to rheumatoid arthritis and in 58% of new admissions to hospital rheumatology unitshospital rheumatology units

Disorders Associated with the Anemia of Disorders Associated with the Anemia of Chronic Disease ACD(1)Chronic Disease ACD(1)

Chronic infectionsChronic infections

- Pulmonary infections: abscesses, tuberculosis - Pulmonary infections: abscesses, tuberculosis

- Subacute bacterial endocarditis - Subacute bacterial endocarditis

- Pelvic inflammatory disease- Pelvic inflammatory disease

- Chronic urinary tract infections- Chronic urinary tract infections

- Chronic fungal disease- Chronic fungal disease

- HIV- HIV infectionsinfections

- Osteomyelitis- Osteomyelitis Chronic, noninfectious inflammationsChronic, noninfectious inflammations

- Rheumatoid arthritis- Rheumatoid arthritis

- - SLESLE (Systemic lupus erythematosus) (Systemic lupus erythematosus)

- Sever- Severee trauma, thermal injury trauma, thermal injury

- Vasculitis- Vasculitis

Disorders Associated with the Anemia of Disorders Associated with the Anemia of Chronic Disease ACD(2)Chronic Disease ACD(2)

Malignant diseasesMalignant diseases-- Solid Solid ccancerancerss- Hodgkin’s and Non-Hodgkin’s - Hodgkin’s and Non-Hodgkin’s LympmhomasLympmhomas- Leukemias- Leukemias- Multiple myeloma- Multiple myeloma

MiscellanousMiscellanous - Alcoholic liver disease- Alcoholic liver disease

IdiopathicIdiopathic ACD ACD

Anemia of chronic disease Anemia of chronic disease (ACD) -laboratory features(1)(ACD) -laboratory features(1)

The anemia is usually mild or moderate ( Hb The anemia is usually mild or moderate ( Hb 7-11g/dl)7-11g/dl)

- lower values are observed in 20-30% of - lower values are observed in 20-30% of patientspatients

The anemia is most often normochromic and The anemia is most often normochromic and normocytic (MCHC and MCV are normal)normocytic (MCHC and MCV are normal)

ESR - usually rapidESR - usually rapid RetiReticculocytes - most often normal or slightly ulocytes - most often normal or slightly

decreased number, increased count is rare decreased number, increased count is rare

Anemia of chronic disease Anemia of chronic disease (ACD) -laboratory features(2)(ACD) -laboratory features(2)

Iron metabolismIron metabolism

1. Serum Iron - decreased (it is necessary for the 1. Serum Iron - decreased (it is necessary for the diagnosis of ACD)diagnosis of ACD)

2. TIBC - reduced or low-normal (N)2. TIBC - reduced or low-normal (N)

33. Serum Ferritin-increased or normal . Serum Ferritin-increased or normal

44. Sideroblasts in the bone marrow-reduced (5-20%). Sideroblasts in the bone marrow-reduced (5-20%)

Anemia of chronic disease Anemia of chronic disease (ACD) -therapy(ACD) -therapy (1)(1)

1. Treatment of the underlying disorder1. Treatment of the underlying disorder

2. Iron supplementation (IS)2. Iron supplementation (IS)

- ACD with chronic infection or - ACD with chronic infection or malignancy IS should be strictly avoidedmalignancy IS should be strictly avoided

- IS benefit patients with ACD associated - IS benefit patients with ACD associated with auto-immune or rheumatic disorders. with auto-immune or rheumatic disorders.

- when ACD is complicated by iron - when ACD is complicated by iron deficiency deficiency (about 27% patients)(about 27% patients)

Anemia of chronic disease Anemia of chronic disease (ACD) -therapy(ACD) -therapy (2)(2)

3. Transfusion demand (about 30% )patients 3. Transfusion demand (about 30% )patients who have low Hb and are symptomatic who have low Hb and are symptomatic

4. Recombinant erythropoietin 10.000 units 3 4. Recombinant erythropoietin 10.000 units 3 times a week i.v. or s.c. 2-3times a week i.v. or s.c. 2-3 doses, in doses, in the the absence of response 20000absence of response 20000 u u, If there is still , If there is still no respose, the treatment should be no respose, the treatment should be discontinued. (in 40% of patients it reduces discontinued. (in 40% of patients it reduces number of transfusions)number of transfusions)

5. Iron chelation with deferoxamine - in some 5. Iron chelation with deferoxamine - in some patients therapy was associated with a rise in patients therapy was associated with a rise in hemoglobin levelhemoglobin level

6. In future anti-TNF-antibodies 6. In future anti-TNF-antibodies

Aplastic and Aplastic and Hypoplastic Hypoplastic

AnemiasAnemiasWhat happens when the bone What happens when the bone

marrow shuts down?marrow shuts down?

Aplastic anemiaAplastic anemia

is a severe, life-threatening syndrome in is a severe, life-threatening syndrome in which production of erythrocytes, WBCs, which production of erythrocytes, WBCs, and platelets have failed.and platelets have failed.

may occur in all age groups and both may occur in all age groups and both genders.genders.

is characterized by is characterized by peripheral peripheral pancytopeniapancytopenia and accompanied by a and accompanied by a hypocellular bone marrow.hypocellular bone marrow.

Hypocellular bone Hypocellular bone marrow in aplastic marrow in aplastic

anemiaanemia

Aplastic anemiaAplastic anemia PathophysiologyPathophysiology::

The primary defect is a reduction in or depletion The primary defect is a reduction in or depletion of hematopoietic precursor of hematopoietic precursor stem cellsstem cells with with decreased production of all cell lines. decreased production of all cell lines.

This may be due to quantitative or qualitative This may be due to quantitative or qualitative damage to the pluripotential stem cell.damage to the pluripotential stem cell.

In rare instances it is the result of abnormal In rare instances it is the result of abnormal hormonal stimulation of stem cell proliferation hormonal stimulation of stem cell proliferation

or the result of a defective bone marrow or the result of a defective bone marrow microenvironment microenvironment

or from cellular or humoral or from cellular or humoral immunosuppression of hematopoiesisimmunosuppression of hematopoiesis..

Aplastic anemiaAplastic anemia EtiologyEtiology

AcquiredAcquired MostMost cases are cases are idiopathicidiopathic Exposure to ionizing radiation. Whole Exposure to ionizing radiation. Whole

body radiation of 300-500 rads can body radiation of 300-500 rads can completely wipe out the bone marrow. completely wipe out the bone marrow. With sublethal doses, the bone marrow With sublethal doses, the bone marrow eventually recovers.eventually recovers.

Chemical agents – with a benzene ring, Chemical agents – with a benzene ring, chemotherapeutic agents, and certain chemotherapeutic agents, and certain insecticides.insecticides.

Idiosyncratic reactions to some Idiosyncratic reactions to some commonly used drugs such as commonly used drugs such as chloramphenicol or quinacrine.chloramphenicol or quinacrine.

Aplastic anemiaAplastic anemia InfectionsInfections – – viral and bacterial viral and bacterial

infections such as infectious infections such as infectious mononucleosis, infectious hepatitis, mononucleosis, infectious hepatitis, CMV, and miliary TB occasionallyCMV, and miliary TB occasionally

PregnancyPregnancy (rare) (rare) Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria – –

this is a stem cell disease in which the this is a stem cell disease in which the membranes of RBCs, WBCs and platelets membranes of RBCs, WBCs and platelets have an abnormality making them susceptible have an abnormality making them susceptible to complement- mediated lysis.to complement- mediated lysis.

Other diseasesOther diseases – preleukemia and – preleukemia and carcinomacarcinoma

Aplastic anemiaAplastic anemia Congenital disordersCongenital disorders

Fanconi’s anemiaFanconi’s anemia – – the disorder usually the disorder usually becomes symptomatic ~ 5 years of age. becomes symptomatic ~ 5 years of age. Congenital defects such as skin Congenital defects such as skin hyperpigmentation and short stature are also hyperpigmentation and short stature are also seen in affected individuals.seen in affected individuals.

Familial aplastic anemia – a subset of Familial aplastic anemia – a subset of Fanconi’s anemia in which the congenital Fanconi’s anemia in which the congenital defects are absent.defects are absent.

Clinical manifestationsClinical manifestations FatigueFatigue Heart palpitationsHeart palpitations PallorPallor InfectionsInfections PetechiaePetechiae Mucosal bleedingMucosal bleeding

Aplastic anemiaAplastic anemia Lab findingsLab findings

Severe pancytopenia with Severe pancytopenia with relative relative lymphocytosislymphocytosis (lymphocytes live a (lymphocytes live a long time)long time)

Normochromic, normocytic RBCs Normochromic, normocytic RBCs (may be slightly macrocytic)(may be slightly macrocytic)

Mild to moderate anisocytosis and Mild to moderate anisocytosis and poikilocytosispoikilocytosis

Decreased reticulocyte countDecreased reticulocyte count Hypocellular bone marrowHypocellular bone marrow with > with >

70% yellow marrow70% yellow marrow

TreatmentTreatment

in untreated cases the prognosis is in untreated cases the prognosis is poorpoor

Remove causative agent, if Remove causative agent, if knownknown

Multiple transfusionsMultiple transfusionsBone marrow transplantBone marrow transplantImmunosuppressionImmunosuppression

Treatment of aplastic Treatment of aplastic anemiaanemia

Supportive care: transfusion of leucocyte-Supportive care: transfusion of leucocyte-depleted red cells and platelets given to depleted red cells and platelets given to prevent HLA alloimmunisation to prevent HLA alloimmunisation to minimise the risk of rejection of a BM minimise the risk of rejection of a BM transplant and to prevent febrile transplant and to prevent febrile transfusion reactionstransfusion reactions

BM transplantation: is the treatment of BM transplantation: is the treatment of choice for pts choice for pts < 20 yrs of age who have an < 20 yrs of age who have an HLA-identical sibling is available. Patients HLA-identical sibling is available. Patients over 45 yrs are not eligible for BMT over 45 yrs are not eligible for BMT whether an HLA-identical donor is whether an HLA-identical donor is available or not, because of the high risk available or not, because of the high risk of GVHDof GVHD

treatmenttreatment

Immunosuppression: used for Immunosuppression: used for patients older than 45 and those in patients older than 45 and those in whom BMT is not available. Anti-whom BMT is not available. Anti-lymphocyte globulin ( ALG) and lymphocyte globulin ( ALG) and cyclosporin are used alone or in cyclosporin are used alone or in combinationcombination

prognosisprognosis

A bad prognosis ( i.e: severe A bad prognosis ( i.e: severe aplastic anemia) is associated with aplastic anemia) is associated with presence 2 of the following:presence 2 of the following:

1.1. Absolute neutrophil count Absolute neutrophil count < 500< 500

2.2. Platelet count < 20000Platelet count < 20000

3.3. Reticulocyte count of 40000/mm3Reticulocyte count of 40000/mm3