Hematopoiesis Overview

Hematopoiesis

• The process of forming blood components from hematopoietic stem cells in the bone marrow.
• Begins in the yolk sac during fetal development, transitions to the liver, and primarily occurs in the bone marrow during the later months of pregnancy.
• Hematopoiesis persists in the sternum and flat bones until late in life, crucial for bone marrow examination via puncture.
• Extra-medullary hematopoiesis can occur in the liver and spleen under conditions of increased blood cell production.
• Erythropoiesis involves hematopoietic stem cells differentiating into myeloid progenitors, then into erythrocytes, a process of maturation culminating in hemoglobin production.
• Reticulocytes, large cells with residual DNA, enter the peripheral blood and mature into erythrocytes.

Anemia

• A reduction in hemoglobin, hematocrit, or red blood cell count below the mean, differing by age and sex.
• Anemia is a sign, not a diagnosis, requiring identification of the underlying cause.
• Hemoglobin levels vary by age, peaking at birth and decreasing during infancy before increasing to adult levels.

Classification and Etiology of Anemia

• Decreased RBC Production: Bone marrow failure (Parvovirus B19, Diamond Blackfan Anemia), or nutritional deficiencies (iron, folic acid, B12, protein).

• Increased RBC Destruction (Hemolysis):

  • Corpuscular: RBC membrane defects (hereditary spherocytosis) or enzyme deficiencies (glucose 6-phosphate dehydrogenase deficiency).
  • Extracorpuscular: Immune (autoimmune hemolytic anemia) or non-immune factors (infections, burns), or hypersplenism (excessive RBC destruction by an enlarged spleen).

• Blood Loss:

  • Acute: Typically results in normocytic, normochromic anemia.
  • Chronic: Repeated small blood losses lead to iron deficiency anemia.

• Laboratory Approach:

  • Complete Blood Count (CBC): Initial step, determining hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW).
  • Reticulocytes: Indicate bone marrow activity.
  • Peripheral Blood Smear Examination: Microscopic assessment of blood cells.

Case Scenario

• Patient: 18-month-old male, pale for 2-3 weeks.
• Clinical Features: Normal appetite and activity, no infections; pale, well-appearing, no bruises or petechiae; clear breath sounds; grade 2 systolic ejection murmur (suggests hyperdynamic circulation).
• CBC Findings: Very low hemoglobin (4.5 g/dL), low hematocrit, significantly low MCV (41 femtoliter; normal at this age is 72 femtoliter).
• Possible Diagnosis: Iron deficiency anemia based on low hemoglobin, low hematocrit, and low MCV. Increased RDW (24 vs. normal 14) is a crucial indicator. Normal white blood cell, platelet, and bilirubin counts suggest the anemia is not hemolytic.
• Blood film analysis reveals small, hypochromic red blood cells (RBCs), anisocytosis (variation in RBC size), and poikilocytosis (variation in RBC shape), and target cells.

Iron Deficiency Anemia - Introduction

• High RDW (24) is a key indicator.
• Other blood counts (white blood cells, platelets, bilirubin) are normal, crucial to assess the type of anemia.
• Hypochromic microcytic anemia, predominantly microcytic, due to elevated RDW.
• Lack of evidence for hemolysis rules out hemolytic causes.
• Blood film shows small and hypochromic RBCs (low hemoglobin), anisocytosis, poikilocytosis, and target cells.
• Strong suggestion for iron deficiency anemia.

Iron Deficiency Anemia

• Iron is essential for hematopoiesis, enzymes, and cellular function.
• Worldwide, iron deficiency is prevalent, especially in infants and children (6-24 months).
• Infants depend on birth iron stores depleted during the first 6 months.
• Breast milk has limited iron, requiring supplementation post-6 months.
• Iron deficiency is more common in developing nations due to malnutrition and lack of access to iron supplement.
• Untreated iron deficiency in children can impact neurodevelopment.

Iron Metabolism and Dietary Intake

• Iron balance (absorption vs loss) is critical.
• Iron deficiency develops when iron intake fails to meet the body's needs over time.
• Heme iron (animal sources: red meat, chicken, fish, eggs) absorbs more effectively.
• Non-heme iron (vegetables, cereals) absorbs less efficiently.
• Breastfed infants require supplementation after 6 months to meet iron demands.
• Formula-fed infants usually have adequate iron.
• Premature babies require earlier supplementation due to lower initial iron stores.

Causes of Iron Deficiency

• Insufficient birth iron stores, common in preterm infants.
• Multiple births often lead to lower iron stores per infant.
• Fetal blood loss during delivery.
• Impaired iron absorption.
• Cow's milk allergy impedes iron absorption.
• Chronic/recurrent blood loss (e.g., bleeding disorders like Von Willebrand disease).
• Inadequate dietary intake, especially with early cow's milk introduction or prolonged exclusive breastfeeding beyond 6 months.
• Breast milk provides iron, but not enough for a growing infant.
• Increased iron in weaning foods/supplements crucial.

Stages of Iron Deficiency

• Stage 1: Iron Depletion: Decreased iron stores and ferritin; normal hemoglobin and blood film.
• Stage 2: Iron Deficiency: Depleted iron stores, low ferritin, reduced circulating iron; erythropoiesis affected; normal hemoglobin; increased RDW and decreased MCV/MCH.
• Stage 3: Iron Deficiency Anemia: Complete depletion; all indicators of iron deficiency with clinically apparent anemia.

Iron Deficiency Anemia: Clinical Manifestations

• Underlying Etiology: Prematurity, malnutrition, feeding problems.
• General Anemia Manifestations: Headaches, insomnia, shortness of breath, fatigue, dizziness, difficulty concentrating, attention problems (children).
• Pallor: Reduced oxyhemoglobin in skin and mucous membranes, evident in palm creases.
• Organ System Manifestations: Anorexia, pica (unusual cravings), pagophagia (ice cravings); short attention span, irritability, learning problems, reduced school performance, growth retardation, increased infections, decreased muscle endurance, fatigue.

Diagnosing Iron Deficiency Anemia

• Clinical Suspicion: History, physical examination (pallor).
• Laboratory Tests: CBC (RBC indices, MCV, MCH), reticulocyte count, blood film.
• Serum Ferritin: Confirmatory test, but levels can be high in acute infections.
• Therapeutic Trial of Iron: Give iron and observe improvement in neuro function, reticulocyte count, and hemoglobin, supporting the diagnosis.

Treatment

• Addressing the Cause: Dietary advice (iron-rich foods), optimizing iron absorption in vegetarians.
• Oral Iron Therapy: 3-6 mg/kg/day elemental iron for 3-6 months post-hemoglobin normalization.
• Monitoring: Regular follow-up to assess improvement and ensure compliance.
• Non-response to oral iron: Investigate chronic blood loss, cow's milk allergy, incorrect diagnosis (e.g., thalassemia), malabsorption, or other co-existing nutritional deficiencies.

Blood Transfusions for Iron Deficiency Anemia

• Transfusions usually unnecessary; iron deficiency anemia is generally well-managed.
• Hemoglobin rarely falls critically low (3-4 g/dL) requiring immediate transfusions.
• Transfusions may be considered for extremely low hemoglobin (under 3-4 g/dL) only after iron supplementation, letting the body produce its own blood cells.