Blood Disorders in Infants: Membrane Abnormalities

Anemia in Children

• Anemia is defined as a decrease in hemoglobin concentration or red blood cell (RBC) volume below healthy levels.
• Cord blood hemoglobin levels: 16.8 g/dL
• 2-week-old: 16.5 g/dL
• 3-month-old: 12.09 g/dL
• 6-month-to-6-year-old: 12.01 g/dL
• 7-12-year-old: 13.01 g/dL

Clinical presentations of Anemia

• General manifestations: pallor, sleepiness, irritability, weakness, decreased exercise tolerance.
• Flow murmur: often present in anemia.
• Shortness of breath on exertion, tachycardia, cardiac dilation, and high-output heart failure can occur. These stem from increasingly severe anemia, regardless of the underlying cause.
• The heart tries to compensate by increasing heart rate (HR) and cardiac output (CO), but this may lead to hyperdynamic circulation and, over time, heart failure.

Classification of Anemia

• Morphological classification: based on RBC size (mean corpuscular volume, MCV).
  • Microcytic: <70 fL
  • Normocytic: 70-90 fL
  • Macrocytic: >90 fL
• Physiological classification: decreased RBC production or increased destruction.
  • Decreased RBC production: ineffective erythropoiesis, failure of erythropoiesis
  • Increased destruction: hemolysis (hyper-splenism), bleeding (blood loss)

Types of Anemia

• Microcytic anemia: iron deficiency anemia, thalassemias, lead poisoning, anemia of chronic disease, sideroblastic anemia
• Normocytic anemia: chronic disease, inflammation, anemia of aplastic, infection, drugs, malignancies, endocrinopathies (hypothyroidism), renal failure, acute bleeding
• Macrocytic anemia: vitamin B12 deficiency, folate deficiency, liver disease, hypothyroidism, other disorders (e.g., diamond-blackfan anemia, aplastic anemia, down syndrome)

Iron Deficiency Anemia (IDA)

• Most common cause of anemia in children.
• 15% frequency rate in children.
• Causes: increased demand, decreased intake, increased loss.
  • Increased demand: growth spurts in children and infants, puberty
  • Decreased intake: poor diet (inability to access sufficient nutrients), poor absorption (e.g., intolerance)
  • Increased loss: GI bleeding, hemolysis, surgical procedures, worm infestation

Iron Absorption

• Enhanced by: orange juice, vitamin C, soy sauce, vinegar
• Inhibited by: tea, coffee, milk, phytate

Forms of Iron in the Body

• Iron in food: meat, beans, and vegetables
• Iron in storage: ferritin (liver, spleen, muscle, bone marrow), hemosiderin (excreted in urine)
• Iron in circulation: recycled from hemoglobin breakdown

Clinical Features of Iron Deficiency Anemia

• CNS manifestations: apathy, irritability, poor concentration, poor muscle tone, cognitive deficits, poor school performance
• Pica (pagophagia): persistent craving and compulsive eating of nonfood substances like ice
• Breath-holding spells: in children.

Oral Signs in Iron Deficiency Anemia (IDA)

• Koilonychia (spoon-shaped nails)
• Atrophic glossitis (beefy red tongue)
• Cheilosis (angular stomatitis)
• Plummer-Vinson syndrome: triad of IDA, esophageal webs, and dysphagia

Lab Findings in Anemia

• Low hemoglobin, low MCV, low MCHC, elevated RDW, microcytic hypochromic red blood cells, anisocytosis with target cells, teardrops, elliptical cells, and fragmented cells
• Increased platelets with normal morphology

Treatment of Anemia

• Oral iron therapy: 3-6 mg/kg/d, divided doses
• Iron therapy results in increased reticulocyte counts within 3-5 days, peaking between 5 and 7 days with increasing hemoglobin levels thereafter)
• Iron medication is continued for 8 weeks after blood values are normalized
• To restore iron stores

Congenital Hypoplastic Anemia (Diamond-Blackfan Anemia)

• Rare congenital bone marrow failure syndrome
• Usually becomes symptomatic in early infancy.
• More than 90% of cases are recognized within the first year of life.
• Characterized by macrocytic anemia, reticulocytopenia, and deficiency or absence of red blood cells (RBC) precursors in an otherwise normal cellular bone marrow.

Associated anomalies in Diamond-Blackfan Anemia

• Microcephaly, micrognathia
• Triphalangeal thumb, bifid thumb
• Heart defects (VSD, ASD, coarctation)
• Genitourinary tract anomalies (absence or horseshoe kidney, hypospadia)
• Short stature

Diagnosis of Diamond-Blackfan Anemia

• Complete blood count: very low number of red blood cells, low hemoglobin
• Low retic count
• Bone marrow sample (biopsy): few new red blood cells

Treatment of Diamond-Blackfan Anemia

• Prednisolone
• Androgens
• Antithymocyte globulin
• Transfusion
• Stem cell transplantation

Thalassemias

• Heterogenous group of inherited disorders characterized by reduced or absent globin chain synthesis.
• Imbalance will leads to ineffective erythropoiesis and shortened RBC lifespan.

Normal Hemoglobin (Hb) in Adults

• Hb A: 2α, 2β (more than 95%)
• Hb F: 2α, 2γ (less than 2.5%)
• Hb A2: 2α, 2δ (2-3.4%)

Beta-Thalassemia Major

• Characterized by severe microcytic, hypochromic anemia
• Detected early in childhood (after 6 months)
• Infants fail to thrive
• Pallor, variable jaundice, abdominal enlargement, hepatosplenomegaly.
• Marked bone changes (due to expansion of marrow space for increased erythropoiesis).
• Characteristic changes in skull, long bones and hand bones (crew-cut skull)

Sickle Cell Disease (SCD)

• Inherited red blood cell disorder
• Normal RBCs are round, move through small tubes to deliver oxygen
• Abnormal HbS polymerizes, forms rigid fibers, distorts RBCs into sickle shapes when deoxygenated
• Consequences: reduced RBC deformability, hemolysis, vaso-occlusion, ischemia and inflammation

Sickle Cell Anemia: Pathophysiology

• Molecular basis; substitution of valine for glutamic acid on beta-globin chain
• Consequences: reduced RBC deformability, hemolysis, vaso-occlusion, ischemia and inflammation.
• Chronic hemolytic anemia.
• Sickle cells adhere to endothelial cells and can activate inflammatory pathways, leading to tissue damage and organ dysfunction

Clinical Features of Pain Crisis

• Sudden onset of severe deep pain (bones, joints, chest, back, and abdomen)
• Pain lasting hours to days
• Accompanying symptoms: swelling, tenderness, fever (if infection is present), tachycardia
• Common sites: dactylitis, long bones (femur, humerus), ribs, and sternum
• Recurrent Crises: chronic pain, organ damage, and avascular necrosis.

G6PD Deficiency

• Deficiency of G6PD is the most common red cell enzyme defect leading to hemolytic anemia.
• X-linked recessive inheritance; high frequency in certain populations (African, Mediterranean, and Asian ancestry).
• Hundreds of G6PD variants are characterized.

G6PD Deficiency: Clinical Presentations

• Neonatal jaundice and episodic acute hemolytic anemia, often induced by infections, certain drugs (including fava beans), or other stressors
• Episodes of hemolysis are associated with pallor, jaundice, hemoglobinuria and sometimes cardiovascular compromise
• Children are asymptomatic between episodes of hemolysis.
• Dark-colored urine ("coca- cola colored urine") is a typical sign

G6PD Deficiency: Triggering Agents

• Medications: antibacterial (sulfonamides, trimethoprim, sulfamethoxazole, nalidixic acid, chloramphenicol, nitrofurantoin), antimalarials (primaquine, pamaquine, chloroquine, quinacrine)
• Chemicals: phenacetin, vitamin K analogs, methylene blue, probenecid, acetylsalicylic acid, phenazopyridine, phenylhydrazine, benzene, naphthalene
• Illness: diabetic acidosis

G6PD Deficiency: Diagnosis

• Fall in hemoglobin and hematocrit
• Free hemoglobin in plasma and urine
• Heinz bodies: precipitated hemoglobin within red blood cells
• Reticulocytosis: increased number of reticulocytes (immature red blood cells)

G6PD Deficiency: Prevention and Treatment

• Prevention of hemolysis is essential.
• Supportive care (e.g., blood transfusions) may be necessary in severe cases or when Hb is <7 g/dL.
• Discontinuing the causative oxidant agent is crucial for recovery.

Hereditary Spherocytosis

• Common inherited abnormality of the red blood cell (RBC) membrane.
• Usually transmitted as an autosomal dominant or less commonly autosomal recessive disorder.
• 25% of patients have no previous family history.
• De-novo mutations or undetected mild disease in parents

Hereditary Spherocytosis: Clinical Presentations

• Neonatal period: hyperbilirubinemia, potentially severe enough to require phototherapy or exchange transfusions.
• Features of anemia: splenomegaly

Hereditary Spherocytosis: Lab Findings

• Normochromic, normocytic anemia
• Hb maintained 6-9 gm/dL
• Spherocytosis (spherical red blood cells)
• Reticulocytosis elevated reticulocytes)

Hereditary Spherocytosis: Treatment

• Splenectomy: removal of spleen to relieve anemia symptoms