Hematology: Anemia Ii

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Types of Iron D/Os

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Iron Deficiency Anemia (IDA)
Anemia of Chronic Inflammation
Sideroblastic Anemias
Iron Overload/Hemochromatosis

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Iron cycles through the body by...

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Absorption in the small intestine -->
Circulation (carried by transferrin)-->
Storage (ferritin) in bone marrow --> incorporated into protoporphyrin IX in the mitochondria of RBC precursors to make heme/Hb

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Iron Deficiency Anemia (IDA)

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Anemia associated with inadequate stores of body iron

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Anemia of chronic inflammation

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Anemia resulting from impaired mobilization of iron

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Sideroblastic anemia

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When Fe stores and mobilization are adequate, but intrinsic RBC defect prevents incorporation of Fe into heme

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Inadequate intake of iron leads to...

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Inability to produce heme/Hb
Decreased production of RBCs

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Increased need of iron in

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Periods of rapid growth
Pregnancy and nursing

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Compartments where iron is distributed

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Storage compartment: ferritin in liver and bone marrow macrophages
Transport compartment: transferrin
Functional compartment: Hb, myoglobin

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Stages of iron deficiency

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Storage Fe depletion (stage 1)
Transport Fe depletion (stage 2)
Functional Fe depletion: IDA (stage 3)

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IDA stage 1

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Decrease in serum ferritin
normal RBC morphology (no evidence of anemai)
Individuals appear healthy

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Most sensitive test for IDA

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Serum ferritin

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IDA stage 2 (Transport iron depletion)

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Exhaustion of the storage pool of iron.
RBC production continues to be normal due to Fe in the transport compartment
Still no anemia or hypochromia
? slight dec in Hb
Fe deficient erythropoeisis
FPEP eccumulates
PResence of BM sideroblasts

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What does sideroblasts indicate?

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No stored iron

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IDA stage 3 (Functional iron depletion)

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Long standing negative iron flow (usually occurring over a period of months to years), depletion of storage Fe and transport Fe leads to the last stage
Presence of anemia
Developing RBCs unable to develop normally
Most significant finding = classic microcytic/hypochromic anemia

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IDA stage 3 lab tests results

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Decreased Hb
Decreased serum iron
Increased TIBC
Decreased ferritin

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IDA stage 2 lab tests results

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Hb= normal
Serum iron= decreased
TIBC= increased
Ferritin= decreased

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IDA stage 1 lab tests results

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Hb= normal
Serum iron= normal
TIBC= normal
Ferritin= decreased

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IDA clinical features

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Pallor (unnatural paleness)
Muscle dysfunction
Inability to regulate body temp when cold or stressed
Gastritis
*Concaved fingernails (koilonychia)
*Inflammation of the tongue (glossitis)

*rarely seen

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What is pica?

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unusual craving for ingesting unnatural, non-food items:
Ice eating (pagophagia)
Dirt/clay eating (geophagia)
Laundry starch eating (amylophagia)

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More prone/susceptible to the development of IDA

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Adolescent, menstruating females = high risk
Pregnant or nursing females = high risk
Infants and growing children
GI diseases (absorption)/bleeding
Elderly widows (“tea and toast”)

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What is the role of ascorbic acid in IDA?

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Enhances the absorption of non-animal sources of iron such as cereal, breads, fruits, and vegetables.

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Tannates (tea)
Bran food (phosphates rich)
Phytates

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Inhibit iron absorption

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Screening test for IDA

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CBC
? classic pic of IDA (microcytic/hypochromic RBCs)
? RDW (>15%)
? Reticulocyte count
? Thrombocytosis
? Poikilocytosis

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Diagnostic tests for IDA

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Serum/plasma iron concentration
Total iron binding capacity (TIBC)
% transferrin saturation
Serum/plasma ferritin (most sensitive)

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IDA specialized tests

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Concentration of heme precursors (FEP/ZPP)
Serum/plasma transferrin receptor
Bone Marrow: usually not indicated for suspected, uncomplicated Fe deficiency

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What is expected in IDA patient BM?

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Mild to moderate erythroid hyperplasia with a decreased M:E ratio
Poorly hemoglobinized normoblasts
cytoplasm asynchrony = cytoplasm matures slower than nucleus
Sideroblasts are markedly reduced/absent

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What is Myeloid:erythroid ratio

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ratio of all granulocytes and precursors to nucleated erythroid precursors in the bone marrow (reference range = 1.5 – 3.3:1 in text or 2 – 4:1)

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IDA treatment/therapy

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return of strength, appetite, well-being within 3 – 5 days (increased retics within 5 – 7 days; maximal response in 7 – 10 days)

Increase in Hb at a rate of about 2 to 4 g/dL every three weeks until the Hb concentration returns to normal.

Anemia is usually alleviated by 6 – 8 weeks

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CHr (Reticulocyte Hb Conc'n)

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Early indicator of a response and begins to increase well in advance of an increase in reticulocytes and hemoglobin

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Who benefits blood transfusion?

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Individuals with active bleeding and/or evidence for end-organ ischemia

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Anemia of chronic inflammation/dz

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Impaired mobilizatiion of iron.
Commonly associated with systemic diseases; chronic infections and inflammation; autoimmune disease; and, malignancies
Arthritis, TB, HIV, malignancies, SLE

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What is hepcidin?

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Hormone produced by hepatocytes to regulate body Fe levels

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Relationship between hepcidin & anemia of chronic inflammation

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Increased hepcidin released from the liver
Hepcidin interferes with ferroportin function
As a result, unable to mobilize Fe from intestine and macrophages

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Anemia of chronic inflammation: peripheral blood smear

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Mild to moderate anemia without reticulocytosis
30 – 40% of patients may develop microcytic/ hypochromic anemia in long standing cases

Inflammatory condition  leukocytosis and/or thrombocytosis

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Anemia of chronic inflammation Fe studies

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Serum iron= low
TIBC= low

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BM findings in anemia of chronic inflammation?

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Erytrhoid hyperplasia

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IDA versus anemia of chronic inflammation

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IDA: serum Fe= dec; TIBC= inc; serum ferritin= dec.
Anemia of chronic inflammation: serum Fe= dec; TIBC= normal/dec; serum ferritin= normal/inc.

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Anemia of critical illness

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Acute event-related anemia (e.g., after surgery, major trauma, myocardial infarction, or sepsis)

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Sideroblastic anemia (SA)

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Involve abnormalities of the enzymes regulating heme synthesis
Microcytic/hypochromic
Fe is abundant in the marrow

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Sideroblastic anemia: BM Fe stain

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Normoblasts with Fe deposits in mitochondria surrounding the nucleus (ringed sideroblasts

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Characteristics of SA

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1. Increase in total body iron;
2. Presence of ringed sideroblasts in the bone marrow

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Acquired SA

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Primary—refractory anemia with ringed sideroblasts (RARS—MDS)
Secondary—to an underlying disease: drugs, toxic substances (chemotherapy), ETOH, Pb

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Hereditary SA

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Defective heme synthesis due to an abnormal delta-aminolevulinate synthetase (ALAS) enzyme

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How does body react in decreased heme synthesis?

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Decreased heme synthesis is interpreted by the body as an increased need for iron  increased iron absorption from the GI tract

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Dz characterized by impaired heme production.

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Porphyrias

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1. Is ringed sideroblast specific to SA?

2. What is the prognosis if seen in other d/o?

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1. No

2. Associated w/ poor prognosis

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SA; Lead poisoning

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Pb interferes with heme synthesis:
1. Conversion of aminolevulinic acid (ALA) to porphobilinogen  increased ALA
2. Incorporation of Fe into protoporphyrin IX  accumulation of Fe and protoporphyrin IX

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SA: laboratory features

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Chronic exposure __> microcytic/ hypochromic anemia
Basophilic stippling , pappenheimer bodies
Poikilocytosis and target cells

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Treatment for SA

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Pb chelation by salts of EDTA  excreted in the urine

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SA: Fe studies

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Increased iron and serum ferritin

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SA: BM findings

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Erythroid hyperplasia
Normoblast are poorly hemoglobinized
Ineffective erythropoietic component

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SA: Therapy

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Phlebotomy
Removal of toxin/drug

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Hemochromatosis

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Clinical disorder that results in tissue/organ damage from excess iron

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Danger of hemochromatosis

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Excess iron deposits are stored not only in macrophages but also in liver cells (hepatocytes), cardiac cells, pancreas, as well as other tissue/organs

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Hereditary Hemochromatosis

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Mutation in the HFE gene (HLA-A locus of chromosome 6)--> excessive absorption & storage of Fe

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Secondary Hemochromatosis

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Associated w/ ineffective erythropoeisis
Chronic liver dz, transfusions, Fe injections/therapy
Alcohol

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Common screening test for hemochromatosis

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Transferrin saturation
>50% for female
>60% for male

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Purpose of hemochromatosis lab testing

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Screen for the condition
Dx the cause if organ damage
Monitor tx

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Hemochromatosis: Lab findings

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> 60% transferrin saturation
Serum ferritin:≥ 95th percentile suggests iron overload
DNA testing is necessary for diagnosing genetic mutation (HFE gene)
Anemia is not usually present (normal erythropoiesis)