17 :Iron Deficiency Anemia: CBC Characteristics

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Questions and Answers

In sideroblastic anemia, what is the primary reason for the accumulation of iron in the mitochondria of erythroblasts?

  • Overproduction of transferrin receptors, causing excessive iron uptake by erythroblasts.
  • Reduced production of hepcidin, resulting in decreased iron sequestration in macrophages.
  • Defective incorporation of iron into heme, leading to its buildup within the mitochondria. (correct)
  • Increased intestinal absorption of iron due to genetic mutations.

In anemia of chronic inflammation (ACI), serum ferritin levels are typically decreased due to iron depletion.

False (B)

What is the underlying mechanism by which lead poisoning leads to sideroblastic anemia?

Lead interferes with the enzymes ferrochelatase and delta-aminolevulinic acid dehydratase, disrupting heme synthesis and causing iron accumulation in mitochondria.

In erythropoietic protoporphyria (EPP), a deficiency in the enzyme ________ leads to the accumulation of protoporphyrin IX in erythrocytes, plasma, and feces.

<p>ferrochelatase</p> Signup and view all the answers

Match the following conditions with their expected serum ferritin levels:

<p>Iron Deficiency Anemia (IDA) = Decreased Anemia of Chronic Inflammation (ACI) = Normal or Increased Sideroblastic Anemia = Usually Increased Iron Overload Conditions = Elevated</p> Signup and view all the answers

Which of the following complete blood count (CBC) characteristics is most indicative of iron deficiency anemia (IDA)?

<p>Microcytic and hypochromic RBCs with elevated RDW. (D)</p> Signup and view all the answers

In hereditary hemochromatosis, the primary cause of iron overload is repeated blood transfusions.

<p>False (B)</p> Signup and view all the answers

Describe the role of hepcidin in the pathogenesis of anemia of chronic inflammation (ACI).

<p>Hepcidin, stimulated by inflammatory cytokines, reduces iron availability by binding to ferroportin, leading to iron retention in macrophages and decreased iron absorption from the gut.</p> Signup and view all the answers

Ringed sideroblasts, a pathognomonic finding in sideroblastic anemia, are characterized by excessive iron deposition in the _________ of developing erythroblasts.

<p>mitochondria</p> Signup and view all the answers

Match the following porphyrias with their corresponding enzyme deficiency:

<p>Congenital Erythropoietic Porphyria (CEP) = Uroporphyrinogen III Synthase Erythropoietic Protoporphyria (EPP) = Ferrochelatase</p> Signup and view all the answers

Which of the following laboratory findings is consistent with iron overload?

<p>Elevated serum ferritin, decreased TIBC, and increased transferrin saturation. (C)</p> Signup and view all the answers

Soluble transferrin receptor (sTfR) levels are typically elevated in anemia of chronic inflammation (ACI).

<p>False (B)</p> Signup and view all the answers

What is the significance of an elevated free erythrocyte protoporphyrin (FEP) level in the context of iron deficiency anemia (IDA)?

<p>Elevated FEP indicates that protoporphyrin cannot be incorporated into heme due to insufficient iron, reflecting impaired heme synthesis.</p> Signup and view all the answers

In anemia of chronic inflammation (ACI), the inflammatory cytokine ________ stimulates the production of hepcidin, which then reduces iron availability.

<p>IL-6</p> Signup and view all the answers

Match the following conditions with their corresponding bone marrow findings:

<p>Iron Deficiency Anemia (IDA) = Decreased or Absent Iron stores Anemia of Chronic Inflammation (ACI) = Normal or Increased Iron stores in Macrophages Sideroblastic Anemia = Ringed Sideroblasts</p> Signup and view all the answers

Which of the following groups is at the highest risk for developing iron deficiency anemia (IDA)?

<p>Elderly individuals with nutritional deficiencies (C)</p> Signup and view all the answers

In sideroblastic anemia, soluble transferrin receptor (sTfR) levels are usually elevated as a compensatory response to iron deficiency.

<p>False (B)</p> Signup and view all the answers

Describe the characteristic features of a Wright-stained bone marrow smear in a patient with sideroblastic anemia.

<p>Presence of ring sideroblasts (erythroid precursors with iron-loaded mitochondria), anisocytosis, poikilocytosis, and basophilic stippling.</p> Signup and view all the answers

In transfusion-related hemosiderosis, Iron Chelation Therapy uses medications like _________ to remove excess iron.

<p>deferoxamine or deferasirox</p> Signup and view all the answers

Match the following conditions with their pathogenesis:

<p>Iron Deficiency Anemia (IDA) = Insufficient iron available for hemoglobin synthesis Anemia of Chronic Inflammation (ACI) = Inflammatory cytokines impair iron utilization Sideroblastic Anemia Secondary to Lead Poisoning = Lead disrupts heme synthesis</p> Signup and view all the answers

Which of the following clinical conditions can predispose a patient to develop anemia of chronic inflammation (ACI)?

<p>Autoimmune diseases such as rheumatoid arthritis (B)</p> Signup and view all the answers

Men are at higher risk for developing iron deficiency anemia compared to women due to menstruation.

<p>False (B)</p> Signup and view all the answers

What is porphyria, and what are its two main types?

<p>Porphyria is a group of disorders caused by buildup of porphyrins. The two main types are acute porphyrias (affecting the nervous system) and cutaneous porphyrias (affecting the skin).</p> Signup and view all the answers

In congenital erythropoietic porphyria (CEP), a deficiency in _________ leads to the accumulation of type I isomers of porphyrins.

<p>uroporphyrinogen III synthase</p> Signup and view all the answers

Match the type of sideroblastic anemia with predisposing factors:

<p>Acquired Sideroblastic Anemia = Alcohol misuse, certain medications, and heavy metal toxicity Hereditary Sideroblastic Anemia = X-linked or autosomal genetic mutations</p> Signup and view all the answers

Which of the following medications is known to potentially trigger sideroblastic anemia?

<p>Anti-tuberculous agents (D)</p> Signup and view all the answers

Repeated blood donations typically lead to iron overload conditions rather than iron deficiency anemia.

<p>False (B)</p> Signup and view all the answers

What are the expected findings on a Prussian blue stain of bone marrow in a patient with sideroblastic anemia?

<p>Presence of ring sideroblasts (erythroid precursors with granules of non-heme iron in a ring around the nucleus) and increased total iron stores.</p> Signup and view all the answers

In erythropoietic protoporphyria (EPP), the primary clinical presentation involves _________ due to the accumulation of protoporphyrin IX.

<p>photosensitivity</p> Signup and view all the answers

Match the descriptions with either Hereditary Hemochromatosis or Transfusion-Related Hemosiderosis

<p>Hereditary Hemochromatosis = Caused by genetic mutations that results in excessive intestinal iron absorption. Transfusion-Related Hemosiderosis = Condition developed from repeated blood transfusions.</p> Signup and view all the answers

Flashcards

Iron Deficiency Anemia (IDA) Etiology

Develops from inadequate iron intake, impaired absorption, or chronic blood loss.

CBC of Iron Deficiency Anemia

HGB and HCT are low, MCV and MCH are low (microcytic, hypochromic), RDW is elevated.

CBC of Anemia of Chronic Inflammation

HGB is low to normal, HCT is low, MCV and MCH are normal to low, RDW is usually normal.

CBC of Sideroblastic Anemia

HGB and HCT are low, MCV is variable, MCH is low to normal, RDW is elevated.

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Lab findings in Iron Deficiency Anemia

Ferritin is decreased, serum iron is low, TIBC is increased, transferrin saturation is low, FEP and sTfR are elevated.

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Lab findings in Latent Iron Deficiency

Ferritin may be low-normal, serum iron & TIBC may be normal, sTfR starts to increase.

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Lab findings in Anemia of Chronic Inflammation

Ferritin is normal or increased, serum iron is decreased, TIBC is low or normal, transferrin saturation is low, sTfR is typically normal.

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Lab findings in Sideroblastic Anemias

Ferritin and Serum Iron are increased, TIBC is normal to low, Transferrin Saturation is increased, sTfR is usually normal.

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Lab findings in Iron Overload Conditions

Ferritin and Serum Iron are elevated, TIBC is low, Transferrin Saturation increased, sTfR is normal or low.

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Groups Most At Risk for IDA

Menstruating, pregnant or nursing women, infants to adolescents and elderly.

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Bone Marrow Smear in IDA

Smaller, pale erythroid precursors plus decreased or absent iron stores.

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Bone Marrow Smear in ACI/AI

Normal or mildly abnormal erythroid precursors plus normal to increased iron stores in macrophages.

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Bone Marrow Smear in Sideroblastic Anemia

Ring sideroblasts as a finding, cells might be different sizes (anisocytosis) and shapes (poikilocytosis), as well as basophilic stippling.

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Anemia of Chronic Inflammation (ACI)

Chronic inflammation causes low circulating iron, with sufficient storage

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Predisposing Factors for Acquired Sideroblastic Anemias

Chronic alcohol, medications, heavy metals, nutritional deficiencies, MDS, & genetic disorders.

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Causes of Elevated FEP

IDA has decreased heme synthesis because of a lack of iron, while lead poisoning interferes with heme synthesis.

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Etiology of Hereditary Hemochromatosis

Is caused by genetic mutations, most commonly in the HFE gene.

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Etiology of Transfusion-Related Hemosiderosis

Secondary iron overload due to repeated blood transfusions.

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Erythropoietic porphyrias Result From

Erythropoietic porphyrias result from inherited enzyme defects in the heme biosynthesis pathway.

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Pathogenesis of IDA

IDA has decreased heme synthesis because of insufficient iron.

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Pathogenesis of ACI

ACI results from chronic inflammatory conditions that lead to decreased iron absorption.

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Sideroblastic Anemia - Lead Pathogenesis

Lead Interferes with Enzymes.

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Porphyria

A group of rare disorders caused by a buildup of natural chemicals called porphyrins in the body.

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Sideroblastic anemia

Inadequate supplies of iron for production of hemoglobin, diseases that interfere with the production of protoporphyrin also can produce anemia

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Study Notes

  • Complete blood count (CBC) results can indicate iron deficiency anemia, anemia of chronic inflammation, and sideroblastic anemias

Iron Deficiency Anemia

  • Develops due to inadequate iron intake, expanded iron needs without compensation, impaired absorption, or chronic hemoglobin loss
  • Inadequate intake can starve the erythron for iron
  • Impaired absorption prevents iron absorption through the enterocyte into the blood
  • Chronic blood loss results from repeated blood donations, hemorrhage, or hemolysis
  • Excessive heme iron loss can occur from gastrointestinal bleeding (ulcers, tumors), or heavy menstrual bleeding

CBC Characteristics

  • Hemoglobin (HGB): Low
  • Hematocrit (HCT): Low
  • Mean Corpuscular Volume (MCV): Low (microcytic)
  • Mean Corpuscular Hemoglobin (MCH): Low (hypochromic)
  • Red Cell Distribution Width (RDW): Elevated, indicating variation in red blood cell (RBC) size
  • RBC Count: Typically low
  • RBC Morphology: Hypochromic and microcytic RBCs, often with increased anisocytosis and poikilocytosis

Anemia of Chronic Inflammation

  • Also known as Anemia of Chronic Disease

CBC Characteristics

  • Hemoglobin (HGB): Low to normal
  • Hematocrit (HCT): Low
  • Mean Corpuscular Volume (MCV): Normal to low (normocytic to microcytic)
  • Mean Corpuscular Hemoglobin (MCH): Normal to low (normochromic to hypochromic)
  • Red Cell Distribution Width (RDW): Usually normal, unless there is a coexisting iron deficiency
  • RBC Count: Low
  • RBC Morphology: Normocytic and normochromic, though microcytic and hypochromic RBCs can occur in cases with concurrent iron deficiency

Sideroblastic Anemias

CBC Characteristics

  • Hemoglobin (HGB): Low
  • Hematocrit (HCT): Low
  • Mean Corpuscular Volume (MCV): Low, normal, or high (microcytic, normocytic, or macrocytic)
  • Mean Corpuscular Hemoglobin (MCH): Low to normal
  • Red Cell Distribution Width (RDW): Elevated
  • RBC Count: Low
  • RBC Morphology: Presence of ringed sideroblasts in the bone marrow, anisocytosis, poikilocytosis, basophilic stippling, and dimorphic RBC population

Iron Deficiency Anemia (IDA)

Classical Iron Studies

  • Serum Ferritin: Decreased levels
  • Serum Iron: Low levels
  • Total Iron Binding Capacity (TIBC): Increased
  • Transferrin Saturation: Low
  • Free Erythrocyte Protoporphyrin (FEP): Elevated
  • sTfR: Elevated

Latent Iron Deficiency

Iron Studies

  • Serum Ferritin: May start to decrease
  • Serum Iron and TIBC: Might not show significant abnormalities
  • Soluble Transferrin Receptor (sTfR): Starts to increase

Anemia of Chronic Inflammation (ACI)

Iron Studies

  • Serum Ferritin: Normal or increased
  • Serum Iron: Decreased
  • TIBC: Usually low or normal
  • Transferrin Saturation: Low
  • sTfR: Typically normal

Sideroblastic Anemias

Iron Studies

  • Serum Ferritin and Serum Iron: Usually increased
  • TIBC: Normal to low
  • Transferrin Saturation: Increased
  • sTfR: Usually normal
  • Bone Marrow: Presence of ringed sideroblasts

Iron Overload Conditions

Iron Studies

  • Serum Ferritin: Elevated
  • Serum Iron: Increased
  • TIBC: Low
  • Transferrin Saturation: Significantly increased, often more than 50%
  • Liver Biopsy or MRI: Increased hepatic iron concentration
  • sTfR: Normal or low

Risk Groups for Iron Deficiency Anemia

  • Women, especially menstruating, pregnant, or nursing women
  • Infants to adolescents
  • Elderly, due to nutritional deficiencies or complications of concurrent disorders
  • Men and post-menopausal women (without menstrual period for 12 months) are at lower risk

Iron Deficiency Anemia (IDA) Bone Marrow Smear

Wright-stained

  • Erythroid precursors are smaller and hypochromatic
  • Increase in erythroid precursors

Prussian blue stain

  • Shows decreased or absent iron stores

Anemia of Chronic Inflammation (ACI/AI) Bone Marrow Smear

Wright-stained

  • Erythroid precursors may be normocytic and normochromic, or mildly microcytic and hypochromatic
  • Presence of adequate or mildly increased erythroid precursors, with ineffective erythropoiesis

Prussian blue stain

  • Shows normal or increased iron stores in bone marrow macrophages

Sideroblastic Anemia Bone Marrow Smear

Wright-stained

  • Presence of ring sideroblasts
  • Cells might be different sizes and shapes

Prussian blue stain

  • Shows presence of ring sideroblasts
  • Total iron stores are usually increased

Clinical Conditions Predisposing to ACI/AI

  • Anemia of chronic inflammation (ACI) occurs due to chronic inflammation from other disorders
  • Ferroportin is blocked, keeping iron inside cells
  • Hepcidin increases with inflammation and suppresses ferroportin

Porphyria Defined

  • A buildup of natural chemicals called porphyrins in the body

Types and Symptoms

  • Acute Porphyrias: Affect the nervous system, causing severe abdominal pain, nausea, vomiting, muscle pain, weakness, and mental changes
  • Cutaneous Porphyrias: Affect the skin, causing sensitivity to sunlight, painful skin redness, swelling, blisters, and changes in skin color

Sideroblastic Anemia Defined

  • Inadequate supplies of iron for production of hemoglobin interferes with protoporphyrin production

Hereditary SAs

  • Mutations can be X-linked or autosomal

Acquired SAs

  • Primary sideroblastic anemia is refractory
  • Secondary sideroblastic anemias are caused by drugs and bone marrow toxins

Predisposing Factors for Acquired Sideroblastic Anemias

  • Alcohol Misuse
  • Medications
  • Heavy Metal Toxicity
  • Nutritional Deficiencies
  • Myelodysplastic Syndromes (MDS)
  • Other Health Challenges

Clinical Significance of Increased FEP Levels

Iron Deficiency Anemia

  • FEP accumulates because it cannot be incorporated into heme without sufficient iron

Lead Poisoning

  • FEP increases due to the inability to progress heme synthesis properly

Anemia of Chronic Disease

  • FEP may be increased due to impaired heme synthesis under inflammatory conditions

Sideroblastic Anemia

  • FEP levels increase because heme synthesis is disrupted

Pathogenesis of Anemias and Hemochromatosis

Iron Deficiency Anemia (IDA)

  • Results from insufficient iron available for hemoglobin synthesis due to inadequate dietary intake, increased demand, poor absorption, or chronic blood loss

Anemia of Chronic Inflammation (ACI)

  • Results from chronic inflammatory conditions, where inflammatory cytokines stimulate hepcidin production, leading to iron restriction

Sideroblastic Anemia Secondary to Lead Poisoning

  • Lead poisoning disrupts heme synthesis by inhibiting critical enzymes, leading to iron accumulation in the mitochondria of erythroblasts

Hereditary Hemochromatosis

Etiology

  • Caused by genetic mutations, most commonly in the HFE gene

Laboratory Diagnosis

  • Serum Ferritin: Elevated
  • Transferrin Saturation: Increased (> 45%)
  • Genetic Testing

Treatment

  • Phlebotomy & Dietary Management

Etiology

  • Secondary iron overload due to repeated blood transfusions

Laboratory Diagnosis

  • Serum Ferritin: Elevated
  • Liver Biopsy or MRI

Treatment

  • Iron Chelation Therapy & Monitoring

Erythropoietic Porphyrias

Congenital Erythropoietic Porphyria (CEP)

  • Caused by a deficiency in the enzyme uroporphyrinogen III synthase
  • Anemia may be present due to hemolytic anemia
  • Elevated levels of uroporphyrin I and coproporphyrin I in urine
  • Photosensitivity, Discolored urine

Erythropoietic Protoporphyria (EPP)

  • Results from a partial deficiency of the enzyme ferrochelatase
  • CBC is often normal
  • Elevated free protoporphyrin levels
  • Non-blistering photosensitivity, Chronic liver disease

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