Notes on Haemolytic Anaemias and Thalassaemias

Haemolytic Anaemias and Thalassaemias

Thalassaemias Overview

• Thalassaemias are characterized by a reduction/deficiency in the synthesis of one or more globin chains.

• Major genotypes include:

  • Alpha chains: ext{α}_ ext{α}/ ext{α}_ ext{α}

  • Beta chains: ext{β}/ ext{β}

• Homozygous forms can lead to total deletion of alpha or beta chains.

Thalassaemia Major

• Genotypes:

  • For alpha chains: ext{α}0/ ext{α}0 or ext{α}+/β+.

  • For beta chains: ext{β}0/ ext{β}0

• Results in:

  • No globin chain produced (in ext{α}0/ ext{β}0)

  • Reduced globin chain production (in ext{α}+/β+)

• Consequences:

  • Decreased hemoglobin (Hb) synthesis

  • Ineffective erythropoiesis leading to chronic hemolytic anemia

  • Microcytic hypochromic anemia

Clinical Presentation of Thalassaemias

• Patients may exhibit:

  • Bony deformities:

  • Skull bossing

  • Hypertrophy of the maxilla

  • Puffy eyes and upper teeth protrusion

  • Compensatory effects from increased erythropoietic marrow:

  • Hepatosplenomegaly

  • Jaundice

  • Potential for hemachromatosis due to frequent blood transfusions and iron overload.

Alpha Thalassaemia Major

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• In the fetus, presents as Hb Barts indicating the genotype ext{- -} / ext{- -}.

• Characteristics:

  • No production of alpha chains; instead, 4 gamma (γ) chains are formed.

  • Hb Barts has high oxygen affinity and is fatal (hydrops fetalis).

  • Symptoms include hypoxia, cardiac failure in utero, and potential mother's toxaemia of pregnancy.

Laboratory Findings in Alpha Thalassaemia Major

• Results in:

  • Microcytic/hypochromic anemia

  • Low indices (Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH))

  • Increased reticulocyte count (retics)

  • No HbA or HbF, increased embryonic Hb (Hb Barts, HbH, Hb Portland)

• Poikilocytes and target cells may be present.

Alpha Thalassaemia in Adults

• Adults may present with HbH, characterized by reduced production of alpha chains and a predominant formation of beta chains (4 beta chains instead of 2 alpha and 2 beta).

• Characteristics include:

  • Unstable HbH with high O2 affinity, leading to tissue hypoxia and cyanosis.

  • Precipitation forms inclusions known as "Golf balls" due to instability.

• Clinical features mimic those of alpha thalassaemia major.

Alpha Thalassaemia Minor

• Laboratory findings indicate:

  • Genotypes could be ext{α}_ ext{α}/ ext{α}- or ext{α}-/ ext{α}_- or ext{α}α/- - .

  • Normal RBCs, HbF, and HbA levels

  • RCC (Red Cell Count) above 5.5 imes 10^{12}/L, with low indices.

Beta Thalassaemia Major

• Associated features include:

  • Distinct facial features (mongoloid appearance).

  • Skull bossing due to overactive bone marrow compensation.

  • Skin hyperpigmentation due to iron overload.

  • Increased susceptibility to infections due to splenic workloads.

  • Can lead to cardiac failure with treatment often including blood transfusion.

Laboratory Findings in Beta Thalassaemia Major

• Presents typically in the first year of life:

  • Failure to thrive

  • Hyperplastic bone marrow with severe microcytic hypochromic anemia

  • Increased reticulocyte and nucleated red cell counts.

  • Poikilocytes, with target cells known as leptocytes.

• Increased Hemoglobin F (HbF) levels detected, normal/slightly increased levels of HbA2.

Beta Thalassaemia Minor

• Laboratory findings include:

  • Low indices (MCV, MCH)

  • RCC greater than 5.5 imes 10^{12}/L

  • Normal RDW (Red Cell Distribution Width)

  • Increased HbA2, slightly increased HbF.

  • Symptoms may be mild, often confused with iron deficiency anemia.

Beta Thalassaemia Screening Techniques

• Mentzer Index:

  • MCV / RCC < 13 suggests thalassemia; if > 13, indicates iron deficiency.

  • MCH < 3.8 suggests thalassemia; if > 3.8, indicates iron deficiency.

• Thal index:

  • ext{MCV}^2 imes ext{RDW} < 65 suggests thalassemia; if > 65, indicates iron deficiency.

• Further investigation is required if thalassaemia is suspected.

Confirmation of Beta Thalassaemia

• Conducted via:

  • Alkaline Hemoglobin Electrophoresis:

  • Distribution patterns of hemoglobin types reveal various conditions.

  • Acid Hemoglobin Electrophoresis:

  • Distinction of hemoglobin variants in beta thalassemia patients is essential for diagnosis.

Hereditary Persistence of Fetal Hemoglobin (HPFH)

• Results from beta globin gene deletions/mutations leading to increased gamma chain production into adulthood.

• Can result in:

  • Absence of HbA and HbA2 if homozygous.

  • Presence of HbA2 if heterozygous.