Microcytic Hypochromic Anemia M Qari

Differential diagnosis of microcytic hypochromic anemia Iron deficiency and iron deficiency anemia The anemia of chronic disorders Sideroblastic anemias Thalassemia Major Lead Poisoning Hereditary pyropoikilocytosis

Iron metabolism Most body iron is present in haemoglobin in circulating red cells The macrophages of the reticuloendotelial system store iron released from haemoglobin as ferritin and haemosiderin They release iron to plasma, where it attaches to transferrin which takes it to tissues with transferrin receptors – especially the bone marrow – where the iron is incorporated by erythroid cells into haemoglobin There is a small loss of iron each day in urine, faeces, skin and nails and in menstruating females as blood (1-2 mg daily) is replaced by iron absorbed from the diet.

RBC-The important players (2) Iron key element in the production of hemoglobin absorption is poor Transferrin iron transporter Ferritin iron binder, measure of iron stores, *also acute phase reactant*

Stages in the development of iron deficiency Prelatent reduction in iron stores without reduced serum iron levels Hb (N), MCV (N), iron absorption (), transferin saturation (N), serum ferritin (), marrow iron () Latent iron stores are exhausted, but the blood haemoglobin level remains normal Hb (N), MCV (N), TIBC (), serum ferritin (), transferin saturation (), marrow iron (absent) Iron deficiency anemia blood haemoglobin concentration falls below the lower limit of normal Hb (), MCV (), TIBC (), serum ferritin (), transferin saturation (), marrow iron (absent)

Iron deficiency and iron deficiency anemia The characteristic sequence of events ensues when the total body iron level begins to fall: 1. decreases the iron stores in the macrophages of the liver, spleen and bone marrow 2. increases the amount of free erythrocyte protoporphiryn (FEP) 3. begins the production of microcytic erythrocytes 4. decreases the blood haemoglobin concentration

Definitions Anemia-values of hemoglobin, hematocrit or RBC counts which are more than 2 standard deviations below the mean HGB<13.5 g/dL (men) <12 (women) HCT<41% (men) <36 (women)

Microcytic Anemia MCV <80 Reduced iron availability Reduced heme synthesis Reduced globin production

Microcytic Anemia REDUCED IRON AVAILABILTY Iron Deficiency Deficient Diet/Absorption Increased Requirements Blood Loss Iron Sequestration Anemia of Chronic Disease Low serum iron, low TIBC, normal serum ferritin MANY!! Chronic infection, inflammation, cancer, liver disease

Microcytic Anemia REDUCED HEME SYNTHESIS Lead poisoning Acquired or congenital sideroblastic anemia Characteristic smear finding: Basophylic stippling

Microcytic Anemia REDUCED GLOBIN PRODUCTION Thalassemias Smear Characteristics Hypochromia Microcytosis Target Cells Tear Drops

Lab tests of iron deficiency of increased severity NORMAL Fe deficiency Without anemia With mild anemia With severe anemia Serum Iron 60-150 <60 <40 Iron Binding Capacity 300-360 300-390 350-400 >410 Saturation 20-50 30 <15 <10 Hemoglobin Normal 9-12 6-7 Serum Ferritin 40-200 <20 0-10

Differential Diagnosis-Revisited Classification by Pathophysiology Blood Loss Decreased Production Increased Destruction

Iron deficiency anemia Definition and etiologic factors The end result of a long period of negative iron balance decreased iron intake inadequate diet, impaired absorption, gastric surgery, celiac disease increased iron loss gastrointestinal bleeding (haemorrhoids, salicylate ingestion, peptic ulcer, neoplasm, ulcerative colitis) excessive menstrual flow, blood donation, disorders of hemostasis increased physiologic requirements for iron infancy, pregnancy, lactation cause unknown (idiopathic hypochromic anemia)

Iron deficiency anemia Clinical manifestation Presentation of underlying disease 37% anemia symptoms 63%

Evaluation of the Patient HISTORY Is the patient bleeding? Actively? In past? Is there evidence for increased RBC destruction? Is the bone marrow suppressed? Is the patient nutritionally deficient? Pica? PMH including medication review, toxin exposure

Evaluation of the Patient (2) REVIW OF SYMPTOMS Decreased oxygen delivery to tissues Exertional dyspnea Dyspnea at rest Fatigue Signs and symptoms of hyperdynamic state Bounding pulses Palpitations Life threatening: heart failure, angina, myocardial infarction Hypovolemia Fatiguablitiy, postural dizziness, lethargy, hypotension, shock and death

Evaluation of the Patient (3) PHYSICAL EXAM •Stable or Unstable? -ABCs -Vitals •Pallor •Jaundice -hemolysis •Lymphadenopathy •Hepatosplenomegally •Bony Pain •Petechiae •Rectal-? Occult blood

Laboratory Evaluation Initial Testing CBC w/ differential (includes RBC indices) Reticulocyte count Peripheral blood smear CBC-red cell indices-size-micro,macro, normo, color(chromasia) WBC-leukopenia should alert to bone marrow suppression Differential-immature forms Retic count-high-indicates increased response to continued hemolysis or blood loss stable anemia w/ low retic is strong evidence for deficient production of RBCs (reduced marrow response) Smear-as above, nuceated RBCs hematologic dz(sickle, thal,hemolytic anemia), things missed by automated counters: schistocytes, RBC parasits, evidence for hemolysis

Laboratory Evaluation (2) Bleeding Serial HCT or HGB Iron Deficiency Iron Studies Hemolysis Serum LDH, indirect bilirubin, haptoglobin, coombs, coagulation studies Bone Marrow Examination Others-directed by clinical indication hemoglobin electrophoresis B12/folate levels

Differential Diagnosis Classification by Pathophysiology Blood Loss Decreased Production Increased Destruction Classification by Morphology Normocytic Microcytic Macrocytic

Symptoms of anemia Fatigue Dizziness Headache Palpitation Dyspnea Lethargy Disturbances in menstruation Impaired growth in infancy

Symptoms of iron deficiency Irritability Poor attention span Lack interest in surroundings Poor work performance Behavioural disturbances Pica Defective structure and function of epithelial tissue especially affected are the hair, the skin, the nails, the tongue, the mouth, the hypopharynx and the stomach Increased frequency of infection

Pica The habitual ingestion of unusual substances earth, clay (geophagia) laundry starch (amylophagia) ice (pagophagia) Usually is a manifestation of iron deficiency and is relieved when the deficiency is treated

Abnormalities in physical examination Pallor of skin, lips, nail beds and conjunctival mucosa Nails - flattened, fragile, brittle, koilonychia, spoon-shaped Tongue and mouth glossitis, angular cheliosis, stomatitis dysphagia (Peterson-Kelly or Plummer-Vinson syndrome (carcinoma in situ) Stomach atrophic gastritis, (reduction in gastric secretion, malabsorbtion) The cause of these changes in iron deficiency is uncertain, but may be related to the iron requirement of many enzymes present in epithelial and other cells

Laboratory findings (1) Blood tests erythrocytes hemoglobin level  the volume of packed red cells (VPRC)  RBC  MCV and MCH  anisocytosis poikilocytosis hypochromia leukocytes normal platelets usually thrombocytosis

Laboratory findings (2) Iron metabolism tests serum iron concentration  total iron-binding capacity  saturation of transferrin  serum ferritin levels  sideroblasts  serum transferrin receptors  FEP 

Management of iron deficiency anemia Correction of the iron deficiency orally intramuscularly intravenously Treatment of the underlying disease

Oral iron therapy The optimal daily dose - 200 mg of elemental iron Ferrous Gluconate 5 tablets/day Fumarate 3 tablets/day sulphate 3 tablets/day iron is absorbed more completely when the stomach is empty it is necessary to continue treatment for 3 - 6 months after the anemia is relived iron absorption is enhanced: vitC, meat, orange juice, fish is inhibited: cereals, tea, milk side effects heartburn, nausea, abdominal cramps, diarrhoea

Failure of oral iron therapy Incorrect diagnosis Complicating illness Failure of the patient to take prescribed medication Inadequate prescription (dose or form) Continuing iron loss in excess of intake Malabsorbtion of iron

Parenteral iron therapy (1) Is indicated when the patient demonstrated intolerance to oral iron loses iron (blood) at a rate to rapid for the oral intake has a disorder of gastrointestinal tract is unable to absorb iron from gastrointestinal tract

Parenteral iron therapy (2) Preparations and administration iron - dextran complex (50mg iron /ml) intramuscularly or intravenously necessary is the test for hypersensitivity the maximal recommended daily dose - 100mg (2ml) total dose is calculated from the amount of iron needed to restore the haemoglobin deficit and to replenish stores iron to be injected (mg) = (15-pts Hb/g%/) x body weight (kg) x 3

Parenteral iron therapy (3) Side effects local: pain at the injection site, discoloration of the skin, lymph nodes become tender for several weeks, pain in the vein injected, flushing, metallic taste systemic: immediate: hypotension, headache, malaise, urticaria, nausea, anphylactoid reactions delayed: lymphadenophaty, myalgia, artralgia, fever