Dr Abdul Mannan FRCPath FCPS
Blood🩸Doctor
Hereditary elliptocytosis (HE) :
Heterogeneous group of disorders defined by elliptocytes in blood due to RBC membrane skeletal protein abnormality
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Etiology/Pathogenesis • Intrinsic membrane protein abnormalities  Alterations in RBC membrane function and shape • Defects in α-spectrin, β-spectrin, band 4.1, and glycophorin C genes  Point mutations, gene deletions or insertions, and mRNA processing defects  Most cases have spectrin defects Clinical Issues • Familial/inherited anemia • > 85% of HE cases asymptomatic • Gene mutation testing generally not warranted • RBC transfusion may be necessary for symptomatic anemia • HPP in neonate confirmed with elliptocytes on maternal/paternal blood smear Microscopic • Elliptocytes on blood smear • Increased polychromasia secondary to bone marrow response to anemia • Bone marrow shows erythroid hyperplasia Top Differential Diagnoses • Blood RBC artifact • Iron deficiency anemia
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Here are two microscopic images showing the characteristic red blood cell morphologies in these conditions:
Hereditary Elliptocytosis
Blood film showing predominance of elliptical/oval-shaped red blood cells without significant fragmentation. Note the "cigar-shaped" appearance of many cells.
Figure 1: Microscopic appearance of red blood cells in Hereditary Elliptocytosis (left)
Hereditary Pyropoikilocytosis
Blood film demonstrating extreme poikilocytosis with elliptocytes, microspherocytes and fragmented red cells. Note the marked variation in size and shape.
Figure 2: Microscopic appearance of red blood cells in Hereditary Pyropoikilocytosis (right)
graph TD;
A["Blood film shows elliptocytes / ovalocytes"] --> B{"Are there marked fragments and bizarre poikilocytes?"};
B -- No --> C["Predominantly neat elliptocytes/ovalocytes"];
C --> C1["Check CBC: MCV normal or mildly low"];
C --> C2["Consider Iron studies"];
C1 --> D{"Ferritin low?"};
D -- Yes --> D1["Iron Deficiency Anaemia with pencil cells"];
D -- No --> D2["Hereditary Elliptocytosis (HE)"];
B -- Yes --> E["Elliptocytes + fragments + microspherocytes + anisopoikilocytosis"];
E --> E1["MCV very low (25–60 fL)"];
E1 --> F["Hereditary Pyropoikilocytosis (HPP)"];
F --> G["Usually infancy/childhood, severe haemolysis, spectrin mutations"];
%% Differentials for fragments
E --> H{"Clinical context of acute haemolysis, thrombocytopenia?"};
H -- Yes --> H1["Microangiopathic haemolytic anaemia (TTP/HUS/DIC)"];
H -- Burns --> H2["Burn-related poikilocytosis"];
%% Outputs
D1:::iron
D2:::he
F:::hpp
H1:::maha
H2:::burn
classDef iron fill:#f9f,stroke:#333,stroke-width:2px;
classDef he fill:#bbf,stroke:#333,stroke-width:2px;
classDef hpp fill:#f96,stroke:#333,stroke-width:2px;
classDef maha fill:#faa,stroke:#333,stroke-width:2px;
classDef burn fill:#cfc,stroke:#333,stroke-width:2px;
Epidemiology • Incidence  Worldwide HE estimated at 1 in 2,000-4,000 individuals  True incidence not known due to many affected individuals being asymptomatic  HPP uncommon
Age  HE presents at young age if symptomatic (~ 10%), otherwise incidental finding later in life  HPP manifests in early infancy due to severe anemia and neonatal jaundice
• Sex  No sex predilection
• Ethnicity
HE, HPP – Worldwide distribution; more common in African and Mediterranean populations (may confer malaria resistance)
HSE – White families of European descent
Southeast Asian ovalocytosis (SAO) – Malaysia, Philippines, Indonesia