96: HEMATOPOIETIC STEM CELLS Component Role in HSC Regulation
Mesenchymal cells Secrete CXCL12, kit ligand
Overview
Endothelial cells Structural + trophic support
• All peripheral blood cells and some tissue-resident cells derive from
hematopoietic stem cells (HSCs). Osteoblasts/Osteoclasts Regulate niche via matrix remodeling
• HSCs produce hundreds of billions of blood cells daily from a pool Macrophages Indirect stem cell regulation
estimated at ~100,000 cells. Megakaryocytes Influence quiescence
• HSC failure (e.g., radiation injury) leads to death within 2–4 weeks Sympathetic neurons Modulate stem cell cycling (esp. aging)
without intervention.
Schwann cells Niche regulation
• Study of hematopoiesis serves as a model for tissue organization and
regulation. ECM proteins e.g., osteopontin, heparan sulfate
• Knowledge of HSC biology is derived largely from animal models and is
often indirect or inferential. EXCESS CAPACITY OF HSCs
• One HSC pool can serially repopulate several hosts in mice.
CARDINAL FUNCTIONS OF STEM CELLS • Regulatory mechanisms differ from those in progenitor cells.
1. Self-Renewal • Erythropoietin & G-CSF affect progenitors, not HSCs directly.
• Ensures stem cell pool is maintained over a lifetime. • HSC location and behavior modified via niche interactions (e.g.,
• Prevents exhaustion of stem cell supply. CXCL12, adhesion molecules).
2. Differentiation
• Generates mature effector cells needed for tissue function. HEMATOPOIETIC STEM CELL DIFFERENTIATION
• Defects → tissue dysfunction, organ failure, or neoplasia. HSC Hierarchy
Division Outcomes 1. HSCs
2. Multipotent progenitors (MPPs)
Division
Result Description 3. Lineage-committed progenitors
Type
o Common lymphoid progenitors (CLPs)
2 stem cells or 2 o Common myeloid progenitors (CMPs)
Symmetric Expands or depletes stem cell pool
differentiated cells ▪ Megakaryocyte-erythroid progenitors (MEPs)
1 stem cell + 1 differentiated Maintains stem cell pool while ▪ Granulocyte-monocyte progenitors (GMPs)
Asymmetric
cell supporting function 4. Precursors → Mature blood cells
Key Features of Differentiation
DEVELOPMENTAL BIOLOGY OF HSCs • Progressive loss of plasticity and proliferative capacity.
• Sequential Hematopoietic Sites: • Differentiation program: fixed ~10–14 days in humans.
1. Yolk sac: embryonic RBCs + tissue macrophages (e.g., • Some lineage bias exists among individual HSCs.
microglia). • Mature cells (e.g., granulocytes) do not proliferate.
2. Aorta-gonad-mesonephros (AGM): generates multipotent
HSCs. SELF-RENEWAL
3. Fetal liver: main site of hematopoiesis mid-gestation.
• HSCs balance:
4. Bone marrow: takes over in 2nd trimester and continues
o Apoptosis
lifelong.
o Differentiation
5. Spleen: temporary site during development.
o Self-renewal
• Circulating HSCs: • Quiescence:
o Present throughout life.
o Deeply quiescent HSCs divide infrequently (months–years).
o Short-lived in circulation (minutes in mice). o Enforced by:
o Can be harvested (e.g., for transplant).
▪ p57/CDKN1c
MOBILITY OF HSCs ▪ Niche signals: angiogenin, IL-18, angiopoietin-1
Trafficking Into Bone Marrow Age-Related Changes
• Rolling adhesion: via CD162/CD44 binding P-/E-selectins. Factor Effect on Aging Stem Cells
• Firm adhesion: via VCAM-1 ↔ VLA-4 (integrin) interaction. ↑ p16INK4a Impairs cycling
• Homing signal: CXCL12 (SDF-1) binding CXCR4 receptor. ↓ Sympathetic input Reduces stem cell activation
Mobilization for Harvest β3-adrenergic stimulation Restores youthful cycling pattern
Agent Mechanism
G-CSF Indirectly reduces CXCL12 → stem cell release MOLECULAR REGULATORS OF SELF-RENEWAL
Plerixafor Direct CXCR4 antagonist Regulator Function / Effect
Clinical Utility Allows peripheral stem cell collection (vs. BM puncture) Bmi-1 (Polycomb group) Maintains self-renewal, represses CDK inhibitors
Gfi-1 Supports HSC maintenance
HEMATOPOIETIC STEM CELL NICHE Hox genes (e.g., HoxB4) Promote HSC self-renewal
• Definition: Specialized microenvironment supporting stem cell DNMT3a, TET2 Epigenetic regulators, mutations → clonal dominance
maintenance and function.
Bone Marrow Niche Components Asxl1 Mutated in MDS, affects chromatin remodeling
,HSCs & CANCER
• Cancers may mirror tissue organization: contain cancer stem cells
(CSCs).
• CSCs exhibit:
o Self-renewal
o Differentiation
o Resistance to therapy
• Cancer initiation may not arise from stem cells, but progenitors
gaining self-renewal properties.
• Founder mutations (e.g., in TET2, DNMT3a, Asxl1) create clonal
expansion → potential malignancy.
ADDITIONAL CAPABILITIES & CLINICAL USE
Experimental/Investigational Uses
• HSCs may aid in vascular or tissue repair (e.g., stroke, MI) – still
controversial.
• Potential for reprogramming into:
o Mature immune cells (e.g., T cells for immunotherapy)
o RBCs, platelets (bypassing donors)
Gene Therapy Applications
Technique Example
Viral vectors Correcting immunodeficiencies
Blocking BCL11a to reactivate fetal globin (SCD,
Antisense therapy
thalassemia)
CRISPR-Cas9 Editing sickle cell mutation
CLINICAL IMPLICATIONS
• Umbilical cord blood:
o Rich in HSCs but limited in number → slow reconstitution.
o Low GVHD risk, useful for underrepresented ethnicities.
• Haploidentical transplants now more common than cord blood in
adults.
• Expanding gene-modified HSCs may reduce cost and improve therapy
delivery.
KEY CONCEPTS TABLE
Concept Description
Central property of HSCs enabling lifelong blood
Self-renewal
production
Differentiation hierarchy Structured steps from HSC to mature cell types
Niche Microenvironment regulating HSC fate
Dormant state protecting long-term stem cell
Quiescence
reserves
Mobilization Process of moving HSCs from marrow to blood
Promising for genetic diseases (e.g., SCD,
Gene-modified HSC therapy
immunodeficiency)
Cancer stem cells Subset of tumor cells with HSC-like properties
Reprogramming & Still experimental; potential for non-hematologic
regenerative use applications
,97: IRON DEFICIENCY AND OTHER HYPOPROLIFERATIVE 1. Negative Iron Balance Increased loss or demand > absorption
ANEMIAS 2. Iron Depletion Low ferritin, normal iron & TIBC, normal RBC indices
3. Iron-deficient Low transferrin saturation (<20%), hypochromic
DEFINITION erythropoiesis reticulocytes
• Hypoproliferative anemias: 4. Iron-deficiency anemia Microcytosis, hypochromia, low Hb, RDW↑
o Normocytic, normochromic RBCs
o Inappropriately low reticulocyte index (<2–2.5) Causes
o Includes: • Increased Demand: pregnancy, adolescence, growth
▪ Early iron deficiency • Increased Loss: menstruation, GI bleeding
▪ Anemia of chronic inflammation • Decreased Absorption: gastrectomy, celiac disease
▪ Anemia of renal disease • Inadequate Intake: poor diet, vegetarianism
▪ Hypometabolic states (protein malnutrition, Clinical Features
endocrine deficiencies) • Anemia symptoms: fatigue, pallor, SOB
▪ Marrow damage (discussed in Chap. 102) • Advanced signs: koilonychia, cheilosis
• Clue: Iron deficiency in males/postmenopausal women suggests GI
IRON METABOLISM
blood loss
• Roles of Iron: Diagnostic Labs
o Oxygen transport via hemoglobin
Test Findings in IDA
o Storage via myoglobin in muscles
o Cofactor in enzymes (e.g., cytochromes) Serum Iron Low (<50 μg/dL)
o Critical for electron transport and energy metabolism TIBC High (>360 μg/dL)
Table 1: Iron Distribution in Body Transferrin Saturation <15%
Compartment Amount (mg) Function
Ferritin Low (<15 μg/L)
Hemoglobin (RBCs) ~2500 O2 transport
RDW Elevated
Storage (Ferritin, Liver) ~1000 Reserve for future use
Reticulocyte count Low
Myoglobin (Muscle) ~300 O2 storage
Red Cell Protoporphyrin Increased (>100 μg/dL)
Enzymes (Cytochromes) ~100 Cellular metabolism
Soluble Transferrin Receptor Increased (if assay available)
Plasma Transferrin ~3 Iron transport
DIFFERENTIAL DIAGNOSIS OF MICROCYTIC ANEMIA
IRON CYCLE IN HUMANS Serum
• Intake: Disorder Ferritin RDW Comments
Iron
o Dietary absorption in duodenum/proximal jejunum
TIBC high, transferrin sat
• Transport: Iron Deficiency Low Low High
low
o Iron binds transferrin in plasma
o Delivered to erythroid precursors via transferrin receptor Thalassemia Normal/↑ Normal/↑ Normal Target cells, high RBC count
• Utilization: Anemia of Low TIBC, transferrin sat
Low Normal/↑ Normal
o Incorporated into heme in RBC precursors Inflammation ~15%
• Recycling: Myelodysplastic
Normal Normal/↑ Variable
Ring sideroblasts, ineffective
o Senescent RBCs phagocytosed by RE system Syndromes erythropoiesis
o Iron is released via ferroportin, rebinds to transferrin
• Storage: TREATMENT OF IRON-DEFICIENCY ANEMIA
o Excess iron stored as ferritin (soluble) and hemosiderin 1. Red Cell Transfusion
(insoluble) • Reserved for symptomatic patients with CV instability or severe anemia
• Also replenishes iron stores
NUTRITIONAL IRON BALANCE 2. Oral Iron Therapy
• Daily Requirement: • Preferred in uncomplicated IDA
o Men: ~1 mg/day • Iron salts (e.g., ferrous sulfate): 50–65 mg elemental iron/tablet
o Women: ~1.4 mg/day
• Dose: Up to 200 mg elemental iron/day in divided doses
• Sources of Loss:
o Menstruation, GI bleeding, skin/gut epithelial shedding • Absorption: Best on empty stomach; enhanced by vitamin C
• Absorption: • Duration: Continue 6–12 months after Hb normalization to replenish
o Regulated by hepcidin stores
o Occurs via DMT-1 (apical) and ferroportin (basolateral) • Response:
o Enhanced by low iron/hepcidin, erythropoietic demand o Reticulocyte count rise in 4–7 days
o Hb rise by ~1 g/dL per week
IRON-DEFICIENCY ANEMIA (IDA) 3. Parenteral Iron Therapy
• Epidemiology: • Indications:
o Most common nutritional deficiency globally o GI intolerance to oral iron
o Affects >1 billion people o Malabsorption
Stages of Iron Deficiency o Need for rapid replenishment (e.g., EPO therapy)
Stage Characteristics
, • Preparations: | Drug | Iron Dose/Infusion | Notes | |------|--------------------|--
-----| | Ferumoxytol | 510 mg | Low risk of reaction | | Iron sucrose | 200
mg | Safe, widely used | | Ferric gluconate | 125 mg | Moderate risk | |
Ferric carboxymaltose | 750 mg | Once-weekly dosing | | Ferric
derisomaltose | 1000 mg | Newer, single-infusion possible |
• Dose Calculation:
o Weight (kg) × 2.3 × (15 - Hb) + 500–1000 mg (stores)
OTHER HYPOPROLIFERATIVE ANEMIAS
1. Anemia of Chronic Inflammation (AI)
• Causes: Infection, inflammation, malignancy, autoimmune disease
• Mechanisms:
o Cytokine-induced EPO suppression (IL-1, TNF, IFN-γ)
o Impaired iron reutilization
o Hepcidin overproduction blocks ferroportin (iron export)
• Lab features:
o Low serum iron, low TIBC
o Normal/↑ ferritin
o Hypoproliferative marrow
o Mild anemia (Hb usually >9 g/dL)
2. Renal Disease
• Inadequate EPO production
• Uremic toxins suppress marrow
• Treatment: Recombinant EPO, iron supplementation
3. Hypometabolic States
• Causes: Hypothyroidism, hypopituitarism, protein-calorie malnutrition
• Feature: Low EPO production
4. Marrow Damage
• Discussed in Chap. 102
SUMMARY
• Iron-deficiency anemia is the most common cause of anemia worldwide
• It progresses through well-defined stages and is associated with
characteristic lab features
• Diagnosis requires integration of clinical context and lab tests (especially
ferritin)
• Treatment depends on severity and etiology; most can be treated with
oral iron
• Anemia of inflammation mimics IDA but differs in ferritin and iron
utilization patterns
• Hepcidin is the central regulator of iron metabolism and is elevated in
inflammation
Mesenchymal cells Secrete CXCL12, kit ligand
Overview
Endothelial cells Structural + trophic support
• All peripheral blood cells and some tissue-resident cells derive from
hematopoietic stem cells (HSCs). Osteoblasts/Osteoclasts Regulate niche via matrix remodeling
• HSCs produce hundreds of billions of blood cells daily from a pool Macrophages Indirect stem cell regulation
estimated at ~100,000 cells. Megakaryocytes Influence quiescence
• HSC failure (e.g., radiation injury) leads to death within 2–4 weeks Sympathetic neurons Modulate stem cell cycling (esp. aging)
without intervention.
Schwann cells Niche regulation
• Study of hematopoiesis serves as a model for tissue organization and
regulation. ECM proteins e.g., osteopontin, heparan sulfate
• Knowledge of HSC biology is derived largely from animal models and is
often indirect or inferential. EXCESS CAPACITY OF HSCs
• One HSC pool can serially repopulate several hosts in mice.
CARDINAL FUNCTIONS OF STEM CELLS • Regulatory mechanisms differ from those in progenitor cells.
1. Self-Renewal • Erythropoietin & G-CSF affect progenitors, not HSCs directly.
• Ensures stem cell pool is maintained over a lifetime. • HSC location and behavior modified via niche interactions (e.g.,
• Prevents exhaustion of stem cell supply. CXCL12, adhesion molecules).
2. Differentiation
• Generates mature effector cells needed for tissue function. HEMATOPOIETIC STEM CELL DIFFERENTIATION
• Defects → tissue dysfunction, organ failure, or neoplasia. HSC Hierarchy
Division Outcomes 1. HSCs
2. Multipotent progenitors (MPPs)
Division
Result Description 3. Lineage-committed progenitors
Type
o Common lymphoid progenitors (CLPs)
2 stem cells or 2 o Common myeloid progenitors (CMPs)
Symmetric Expands or depletes stem cell pool
differentiated cells ▪ Megakaryocyte-erythroid progenitors (MEPs)
1 stem cell + 1 differentiated Maintains stem cell pool while ▪ Granulocyte-monocyte progenitors (GMPs)
Asymmetric
cell supporting function 4. Precursors → Mature blood cells
Key Features of Differentiation
DEVELOPMENTAL BIOLOGY OF HSCs • Progressive loss of plasticity and proliferative capacity.
• Sequential Hematopoietic Sites: • Differentiation program: fixed ~10–14 days in humans.
1. Yolk sac: embryonic RBCs + tissue macrophages (e.g., • Some lineage bias exists among individual HSCs.
microglia). • Mature cells (e.g., granulocytes) do not proliferate.
2. Aorta-gonad-mesonephros (AGM): generates multipotent
HSCs. SELF-RENEWAL
3. Fetal liver: main site of hematopoiesis mid-gestation.
• HSCs balance:
4. Bone marrow: takes over in 2nd trimester and continues
o Apoptosis
lifelong.
o Differentiation
5. Spleen: temporary site during development.
o Self-renewal
• Circulating HSCs: • Quiescence:
o Present throughout life.
o Deeply quiescent HSCs divide infrequently (months–years).
o Short-lived in circulation (minutes in mice). o Enforced by:
o Can be harvested (e.g., for transplant).
▪ p57/CDKN1c
MOBILITY OF HSCs ▪ Niche signals: angiogenin, IL-18, angiopoietin-1
Trafficking Into Bone Marrow Age-Related Changes
• Rolling adhesion: via CD162/CD44 binding P-/E-selectins. Factor Effect on Aging Stem Cells
• Firm adhesion: via VCAM-1 ↔ VLA-4 (integrin) interaction. ↑ p16INK4a Impairs cycling
• Homing signal: CXCL12 (SDF-1) binding CXCR4 receptor. ↓ Sympathetic input Reduces stem cell activation
Mobilization for Harvest β3-adrenergic stimulation Restores youthful cycling pattern
Agent Mechanism
G-CSF Indirectly reduces CXCL12 → stem cell release MOLECULAR REGULATORS OF SELF-RENEWAL
Plerixafor Direct CXCR4 antagonist Regulator Function / Effect
Clinical Utility Allows peripheral stem cell collection (vs. BM puncture) Bmi-1 (Polycomb group) Maintains self-renewal, represses CDK inhibitors
Gfi-1 Supports HSC maintenance
HEMATOPOIETIC STEM CELL NICHE Hox genes (e.g., HoxB4) Promote HSC self-renewal
• Definition: Specialized microenvironment supporting stem cell DNMT3a, TET2 Epigenetic regulators, mutations → clonal dominance
maintenance and function.
Bone Marrow Niche Components Asxl1 Mutated in MDS, affects chromatin remodeling
,HSCs & CANCER
• Cancers may mirror tissue organization: contain cancer stem cells
(CSCs).
• CSCs exhibit:
o Self-renewal
o Differentiation
o Resistance to therapy
• Cancer initiation may not arise from stem cells, but progenitors
gaining self-renewal properties.
• Founder mutations (e.g., in TET2, DNMT3a, Asxl1) create clonal
expansion → potential malignancy.
ADDITIONAL CAPABILITIES & CLINICAL USE
Experimental/Investigational Uses
• HSCs may aid in vascular or tissue repair (e.g., stroke, MI) – still
controversial.
• Potential for reprogramming into:
o Mature immune cells (e.g., T cells for immunotherapy)
o RBCs, platelets (bypassing donors)
Gene Therapy Applications
Technique Example
Viral vectors Correcting immunodeficiencies
Blocking BCL11a to reactivate fetal globin (SCD,
Antisense therapy
thalassemia)
CRISPR-Cas9 Editing sickle cell mutation
CLINICAL IMPLICATIONS
• Umbilical cord blood:
o Rich in HSCs but limited in number → slow reconstitution.
o Low GVHD risk, useful for underrepresented ethnicities.
• Haploidentical transplants now more common than cord blood in
adults.
• Expanding gene-modified HSCs may reduce cost and improve therapy
delivery.
KEY CONCEPTS TABLE
Concept Description
Central property of HSCs enabling lifelong blood
Self-renewal
production
Differentiation hierarchy Structured steps from HSC to mature cell types
Niche Microenvironment regulating HSC fate
Dormant state protecting long-term stem cell
Quiescence
reserves
Mobilization Process of moving HSCs from marrow to blood
Promising for genetic diseases (e.g., SCD,
Gene-modified HSC therapy
immunodeficiency)
Cancer stem cells Subset of tumor cells with HSC-like properties
Reprogramming & Still experimental; potential for non-hematologic
regenerative use applications
,97: IRON DEFICIENCY AND OTHER HYPOPROLIFERATIVE 1. Negative Iron Balance Increased loss or demand > absorption
ANEMIAS 2. Iron Depletion Low ferritin, normal iron & TIBC, normal RBC indices
3. Iron-deficient Low transferrin saturation (<20%), hypochromic
DEFINITION erythropoiesis reticulocytes
• Hypoproliferative anemias: 4. Iron-deficiency anemia Microcytosis, hypochromia, low Hb, RDW↑
o Normocytic, normochromic RBCs
o Inappropriately low reticulocyte index (<2–2.5) Causes
o Includes: • Increased Demand: pregnancy, adolescence, growth
▪ Early iron deficiency • Increased Loss: menstruation, GI bleeding
▪ Anemia of chronic inflammation • Decreased Absorption: gastrectomy, celiac disease
▪ Anemia of renal disease • Inadequate Intake: poor diet, vegetarianism
▪ Hypometabolic states (protein malnutrition, Clinical Features
endocrine deficiencies) • Anemia symptoms: fatigue, pallor, SOB
▪ Marrow damage (discussed in Chap. 102) • Advanced signs: koilonychia, cheilosis
• Clue: Iron deficiency in males/postmenopausal women suggests GI
IRON METABOLISM
blood loss
• Roles of Iron: Diagnostic Labs
o Oxygen transport via hemoglobin
Test Findings in IDA
o Storage via myoglobin in muscles
o Cofactor in enzymes (e.g., cytochromes) Serum Iron Low (<50 μg/dL)
o Critical for electron transport and energy metabolism TIBC High (>360 μg/dL)
Table 1: Iron Distribution in Body Transferrin Saturation <15%
Compartment Amount (mg) Function
Ferritin Low (<15 μg/L)
Hemoglobin (RBCs) ~2500 O2 transport
RDW Elevated
Storage (Ferritin, Liver) ~1000 Reserve for future use
Reticulocyte count Low
Myoglobin (Muscle) ~300 O2 storage
Red Cell Protoporphyrin Increased (>100 μg/dL)
Enzymes (Cytochromes) ~100 Cellular metabolism
Soluble Transferrin Receptor Increased (if assay available)
Plasma Transferrin ~3 Iron transport
DIFFERENTIAL DIAGNOSIS OF MICROCYTIC ANEMIA
IRON CYCLE IN HUMANS Serum
• Intake: Disorder Ferritin RDW Comments
Iron
o Dietary absorption in duodenum/proximal jejunum
TIBC high, transferrin sat
• Transport: Iron Deficiency Low Low High
low
o Iron binds transferrin in plasma
o Delivered to erythroid precursors via transferrin receptor Thalassemia Normal/↑ Normal/↑ Normal Target cells, high RBC count
• Utilization: Anemia of Low TIBC, transferrin sat
Low Normal/↑ Normal
o Incorporated into heme in RBC precursors Inflammation ~15%
• Recycling: Myelodysplastic
Normal Normal/↑ Variable
Ring sideroblasts, ineffective
o Senescent RBCs phagocytosed by RE system Syndromes erythropoiesis
o Iron is released via ferroportin, rebinds to transferrin
• Storage: TREATMENT OF IRON-DEFICIENCY ANEMIA
o Excess iron stored as ferritin (soluble) and hemosiderin 1. Red Cell Transfusion
(insoluble) • Reserved for symptomatic patients with CV instability or severe anemia
• Also replenishes iron stores
NUTRITIONAL IRON BALANCE 2. Oral Iron Therapy
• Daily Requirement: • Preferred in uncomplicated IDA
o Men: ~1 mg/day • Iron salts (e.g., ferrous sulfate): 50–65 mg elemental iron/tablet
o Women: ~1.4 mg/day
• Dose: Up to 200 mg elemental iron/day in divided doses
• Sources of Loss:
o Menstruation, GI bleeding, skin/gut epithelial shedding • Absorption: Best on empty stomach; enhanced by vitamin C
• Absorption: • Duration: Continue 6–12 months after Hb normalization to replenish
o Regulated by hepcidin stores
o Occurs via DMT-1 (apical) and ferroportin (basolateral) • Response:
o Enhanced by low iron/hepcidin, erythropoietic demand o Reticulocyte count rise in 4–7 days
o Hb rise by ~1 g/dL per week
IRON-DEFICIENCY ANEMIA (IDA) 3. Parenteral Iron Therapy
• Epidemiology: • Indications:
o Most common nutritional deficiency globally o GI intolerance to oral iron
o Affects >1 billion people o Malabsorption
Stages of Iron Deficiency o Need for rapid replenishment (e.g., EPO therapy)
Stage Characteristics
, • Preparations: | Drug | Iron Dose/Infusion | Notes | |------|--------------------|--
-----| | Ferumoxytol | 510 mg | Low risk of reaction | | Iron sucrose | 200
mg | Safe, widely used | | Ferric gluconate | 125 mg | Moderate risk | |
Ferric carboxymaltose | 750 mg | Once-weekly dosing | | Ferric
derisomaltose | 1000 mg | Newer, single-infusion possible |
• Dose Calculation:
o Weight (kg) × 2.3 × (15 - Hb) + 500–1000 mg (stores)
OTHER HYPOPROLIFERATIVE ANEMIAS
1. Anemia of Chronic Inflammation (AI)
• Causes: Infection, inflammation, malignancy, autoimmune disease
• Mechanisms:
o Cytokine-induced EPO suppression (IL-1, TNF, IFN-γ)
o Impaired iron reutilization
o Hepcidin overproduction blocks ferroportin (iron export)
• Lab features:
o Low serum iron, low TIBC
o Normal/↑ ferritin
o Hypoproliferative marrow
o Mild anemia (Hb usually >9 g/dL)
2. Renal Disease
• Inadequate EPO production
• Uremic toxins suppress marrow
• Treatment: Recombinant EPO, iron supplementation
3. Hypometabolic States
• Causes: Hypothyroidism, hypopituitarism, protein-calorie malnutrition
• Feature: Low EPO production
4. Marrow Damage
• Discussed in Chap. 102
SUMMARY
• Iron-deficiency anemia is the most common cause of anemia worldwide
• It progresses through well-defined stages and is associated with
characteristic lab features
• Diagnosis requires integration of clinical context and lab tests (especially
ferritin)
• Treatment depends on severity and etiology; most can be treated with
oral iron
• Anemia of inflammation mimics IDA but differs in ferritin and iron
utilization patterns
• Hepcidin is the central regulator of iron metabolism and is elevated in
inflammation
