Hemoglobin Disorders

Section 6: Hemoglobin Disorders

A. Hemoglobinopathies

Sickle Cell Disease

  • Causes

    • Substitution of glutamic acid → valine at 6th position of the β-globin chain
    • Homozygous SS genotype

  • Laboratory findings

    • Decreased hemoglobin (Hb) and increased white blood cells (WBC)
    • Reticulocytes: very high count
    • Presence of:
    • Drepanocytes (sickle-shaped red blood cells)
    • Target cells
    • Basophilic stippling
    • Howell-Jolly bodies
    • Positive solubility test (sickledex)
    • Hemoglobin electrophoresis for confirmation:
    • Majority of Hb S with increased Hb F
    • Absence of Hb A

  • Clinical Presentation

    • Vaso-occlusive crises (pain crises)
    • Aplastic crises
    • Enlarged heart (cardiomegaly)
    • Progressive loss of pulmonary or renal function
    • Stroke
    • Arthritis
    • Liver damage

  • Treatment

    • Transfusion of blood when necessary
    • Bone marrow transplant
    • Gene therapy
    • Crisis management strategies
Hemoglobin C Disease

  • Cause

    • Substitution of glutamic acid → lysine at 6th position of the β-globin chain

  • Laboratory findings

    • Presence of Hb C crystals and target cells
Hemoglobin SC Disease

  • Causes

    • Inheritance of one Hb S gene and one Hb C gene

  • Laboratory findings

    • Presence of target cells, folded erythrocytes
    • Occasionally, intracellular crystals

  • Clinical Presentation

    • Similar to sickle cell anemia but less severe
    • Associated with splenomegaly
Hemoglobin D Disease
  • Asymptomatic condition
    • Possible finding: Target cells may be observed on peripheral smear
Hemoglobin E Disease
  • Commonly found in Southeast Asia
    • Symptoms can appear in both heterozygous and homozygous forms
    • Cause:
    • Substitution of glutamic acid → lysine at 26th position of the β-globin chain
Hemoglobin H Disease
  • Characterized by mild to severe chronic hemolytic anemia
  • Associated with the absence of 3/4 of the α-globin genes
  • High prevalence in Southeast Asia, Mediterranean islands, and the Middle East

B. Thalassemias

Alpha Thalassemia

  • Causes

    • Deletion of one or more of the four α-globin genes
    1. Silent carrier (1 deletion): Asymptomatic; normal laboratory results
    2. Trait (2 deletions): Mild microcytic anemia
    3. Hb H Disease (3 deletions): Chronic hemolytic anemia
    4. Hydrops Fetalis (4 deletions): Incompatible with life; results in stillbirth

  • Laboratory findings

    • Small "golf ball" inclusions visible with Brilliant Cresyl Blue stain
    • Electrophoresis: Presence of Hb H (fast-moving band)
Beta Thalassemia

  • Causes

    • Little to no β-chain production
    • Results in:
    • Excess accumulation of unstable α-globin chains
    • Ineffective erythropoiesis
    • Shortened red cell survival

  • Laboratory findings

    • Decreased levels of hemoglobin, hematocrit, and red cell count
    • Elevated reticulocyte count
    • Electrophoresis: Predominantly Hb F up to 90%
    • Peripheral smear findings:
    • Microcytic and hypochromic red blood cells
    • Anisocytosis and poikilocytosis
    • Serum ferritin may be increased

  • Clinical Presentation

  • Treatment

    • Blood transfusions
    • Bone marrow or peripheral stem cell (PSC) transplant
    • Strategies to prevent iron overload