RBC DO: MICROCYTIC / HYPOCHROMIC ANEMIA

Iron deficiency anemia

Most common form of anemia world widely

Iron deficiency anemia

It is an example of a nutritional anemia

Iron deficiency anemia

ETIOLOGY

• Inadequate intake of iron

• Increase demand (e.g., Pregnancy, infancy, and childhood)

• Impaired iron absorption (e.g., Celiac disease and decrease stomach acidity)

• Chronic blood loss (e.g., Chronic GI bleeding, prolong menorrhagia, fibroid tumors, or hemorrhoids)

Iron deficiency anemia

Clinical signs and symptoms

Fatigue, weakness, and shortness of breath, especially with exertion, sore tongue (glossitis), inflamed cracks at the corners of the mouth (angular cheilosis), Koilonychia (spooning of the fingernails) may be seen if the deficiency is long-standing. Patients also may experience cravings for nonfood items, called pica.

Functional

IRON COMPARTMENTS IN NORMAL HUMAN

Hemoglobin iron in the blood

Functional

IRON COMPARTMENTS IN NORMAL HUMAN

Myoglobin iron in muscles

Functional

IRON COMPARTMENTS IN NORMAL HUMAN

Peroxidase, catalase, cytochromes, riboflavin enzymes in all cells

Storage

IRON COMPARTMENTS IN NORMAL HUMAN

Ferritin and hemosiderin mostly in macrophages and hepatocytes; small amounts in all cells except mature RBC

Transport

IRON COMPARTMENTS IN NORMAL HUMAN

Transferrin in plasma

1 - STORAGE DEPLETION

STAGES OF IDA

Hemoglobin: NORMAL

Serum Iron: NORMAL

TIBC:NORMAL

Ferritin: DECREASED

2 - TRANSPORT DEPLETION

STAGES OF IDA

Hemoglobin: NORMAL

Serum Iron: DECREASED

TIBC: INCREASED

Ferritin: DECREASED

3 - Functional depletion / Frank’s/ Full-Blown IDA

STAGES OF IDA

Hemoglobin: DECREASED

Serum Iron: DECREASED

TIBC: INCREASED

Ferritin: DECREASED

1. Hookworms

2. Trichuris trichiura

3. Schistosoma mansoni

4. Schistosoma haematobium

Parasites associated with IDA

Anemia of Chronic disease/Inflammation

The Second most common type of anemia world widely

Anemia of Chronic disease/Inflammation

It is the most common anemia in hospitalized patient (nosocomial anemia)

Anemia of Chronic disease/Inflammation

Commonly associated with systemic diseases, including chronic inflammatory conditions such as rheumatoid arthritis, chronic infections such as tuberculosis or human immunodeficiency virus infection, and malignancies

Anemia of Chronic disease/Inflammation

ETIOLOGY

Due to inability to use available iron for hemoglobin production

Anemia of Chronic disease/Inflammation

ETIOLOGY

Impaired release of storage iron associated with increased Acute phase reactants such as Hepcidin (decreases release of iron from stores), Ferritin, and Lactoferrin

Sideroblastic anemia

Caused by blocks in the protoporphyrin pathway resulting in defective hemoglobin synthesis and iron overload

Sideroblastic anemia

In this type of anemia, the body has adequate iron but is unable to incorporate it into hemoglobin synthesis. The iron enters the developing erythrocyte but then accumulates in the perinuclear mitochondria of metarubricytes

Ring sideroblasts

is an erythroid precursor containing at least five iron granules per cell, and these iron-containing mitochondria must circle at least one-third of the nucleus

ringed sideroblasts

Sideroblastic anemia

From 10% to 40% of the nucleated erythrocytes in the bone marrow are

Sideroblastic anemia

Excess iron accumulates in the mitochondrial region of the mature RBC in circulation; cells are called ringed siderocytes; inclusions are siderotic granules (Pappenheimer bodies on Wright’s- stained smears)

Perl’s Prussian blue stain

Sideroblasts and Siderocytes are best demonstrated using

Sideroblastic anemia

ETIOLOGY

♥ Miscellaneous disorders (e.g., uremia, thyrotoxicosis, and porphyria)

Sideroblastic anemia

ETIOLOGY

♥ Idiopathic -unknown cause

Sideroblastic anemia

ETIOLOGY

♥ Toxins, including alcohol, and chronic lead poisoning

Sideroblastic anemia

ETIOLOGY

♥ Secondary to drugs: isoniazid (INH), chloramphenicol; after chemotherapy

Sideroblastic anemia

ETIOLOGY

♥ Association with malignant marrow disorders: acute myelogenous leukemia,

polycythemia vera, myeloma, myelodysplastic syndromes

Sideroblastic anemia

ETIOLOGY

♥ Acquired defect: primary (one of the myelodysplastic syndromes); may evolve into

acute myelogenous leukemia

Sideroblastic anemia

ETIOLOGY

♥ Congenital defect: hereditary sex linked (primarily males); autosomal

Primary

Types of Sideroblastic anemia that is irreversible; causes of block is unknown

Secondary

Types of Sideroblastic anemia that is reversible; causes include alcohol, anti-TB drugs, Chloramphenicol

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Anemia, when present in lead poisoning, is most often normocytic and normochromic; however, with chronic exposure to lead, a microcytic, hypochromic clinical picture may be seen (t/f)

lead poisoning

Multiple blocks in the protoporphyrin pathway that affect heme synthesis

lead poisoning

Presence of many coarse Basophilic stipplings

lead poisoning

what will lead to acquired sideroblastic anemia and acquired porphyria

lead poisoning

It inhibits ferrochelatase and D-ala synthase enzyme in Heme/Protoporphyrin pathway

Iron Deficiency Anemia (IDA)

LABORATORY FEATURES IN MICROCYTIC / HYPOCHROMIC ANEMIAS

SERUM IRON: ↓

SERUM TIBC: ↑

% SATURATION: ↓

% SIDEROBLASTS: ↓

IRON STORES: ↓

SERUM FERRITIN: ↓

ZPP: ↑

Hb A2: N-↓

Hb F: N

Beta thalassemia

LABORATORY FEATURES IN MICROCYTIC / HYPOCHROMIC ANEMIAS

SERUM IRON: N(↑)

SERUM TIBC: N

% SATURATION: N

% SIDEROBLASTS: N(↑)

IRON STORES: N-↑

SERUM FERRITIN: N-↑

ZPP: N

Hb A2: ↑

Hb F: N-↑

Anemia of chronic dx

LABORATORY FEATURES IN MICROCYTIC / HYPOCHROMIC ANEMIAS

SERUM IRON: ↓

SERUM TIBC: N-↓

% SATURATION: ↓

% SIDEROBLASTS: ↓

IRON STORES: N-↑

SERUM FERRITIN: N-↑

ZPP: ↑

Hb A2: N

Hb F: N

Sideroblastic anemia

LABORATORY FEATURES IN MICROCYTIC / HYPOCHROMIC ANEMIAS

SERUM IRON: ↑

SERUM TIBC: ↓

% SATURATION: ↑

% SIDEROBLASTS: ↑

IRON STORES: ↑

SERUM FERRITIN: ↑

ZPP: ↑

Hb A2: N

Hb F: N-↑

Serum Iron

Indicator of available transport iron

Serum Iron

Used for the differential diagnosis of disorders of iron metabolism

non hemolyzed serum and should be obtained in the morning (because serum iron levels may be approximately 25 % lower in the evening)

Spx of Serum Iron

12 hrs

How many hours of fasting is required for Serum Iron

12 hrs

How many hours of fasting is required for TIBC

50 to 160 ug/dl

ref range of Serum iron

250 to 400 ug/dl

ref range of TIBC

40 to 400 ng/ml (rodaks)

Men: 15 to 200 ug/ L

Women:12 to 150 ug/L

ref range of Serum Ferritin

<50 ug/dl of RBC (approximate only bc it depends on the method being used )

ref range of Free Erythrocyte Protoporphyrin

Total iron binding capacity (TIBC)

Indirect indicator of iron stores

Total iron binding capacity (TIBC)

Indirectly measures the concentration of transferrin by measuring its ability to bind iron

non hemolyzed serum

Spx of TIBC

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TIBC Values are independent on the time of day the sample is drawn (t/f)

Serum Ferritin

Reveals the body’s tissue on iron stores

Serum Ferritin

♥ Good indicator of iron storage status

Serum Ferritin

♥ Useful in diagnosis of iron deficiency

Serum Ferritin

♥ Generally, the first laboratory test to become abnormal when iron stores become to decline

Serum Ferritin

♥ Measured using radioimmunoassay

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Free Erythrocyte Protoporphyrin (t/f)

RBCs produce slightly more protoporphyrin than is necessary, but in iron deficiency, protoporphyrin levels build up in RBCs to several times the normal

Free Erythrocyte Protoporphyrin

May be measured directly by a hemato-fluorometer or by an extraction and fluorescence method

Free Erythrocyte Protoporphyrin

♥ Differentiating thalassemia, IDA, & anemia of chronic infection

% Transferrin saturation = Serum Iron / TIBC x 100

Formula of % Transferrin saturation

Perl’s Prussian blue (Rous-test) stain

is actually a chemical compound with the formula Fe7(CN). The compound forms during the staining process, which uses acidic potassium ferrocyanide as the reagent/ stain

Perl’s Prussian blue (Rous-test) stain

is considered the gold standard for assessment of body iron stores.

Perl’s Prussian blue (Rous-test) stain

It is used to confirm hemosiderinuria

diffuse cytoplasmic blueness

Perl’s Prussian blue (Rous-test) stain in Ferric reaction

ferritin is not typically detected, likely because of the intact protein cage. In high concentration, it can appear as a -

dark blue granules

Perl’s Prussian blue (Rous-test) stain in Hemosiderin reaction

hemosiderin stains readily, forming distinct -

Lower right quadrant

In Thomas Plot TRUE IDA is located in what quadrant

Lower left quadrant

In Thomas Plot FUNCTIONAL IDA is located in what quadrant

Upper right quadrant

In Thomas Plot LATENT IDA is located in what quadrant