Diagnosis: Hereditary Elliptocytosis with Active Hemolysis
The peripheral blood smear findings of elliptocytes, microcytes, anisocytosis, and marked polychromatophilia are diagnostic of hereditary elliptocytosis (HE) with active hemolysis. 1, 2
Key Diagnostic Features
The combination of morphologic findings on your smear points specifically to HE rather than other hereditary hemolytic anemias:
Elliptocytes are the pathognomonic feature of HE, distinguishing it from hereditary spherocytosis (which shows spherocytes) and pyruvate kinase deficiency (which shows relatively normal morphology) 1, 3, 4
Microcytes and marked anisocytosis indicate red cell fragmentation, which is the cellular hallmark that correlates with severity of hemolysis in HE 2. The extent of microcytosis directly reflects the degree of cell fragmentation and predicts clinical severity 2
Marked polychromatophilia (elevated reticulocytes) confirms active hemolysis and bone marrow compensation 1
Confirm the Diagnosis
Order these specific tests to confirm HE and assess severity:
Direct antiglobulin test (Coombs) - must be negative to exclude autoimmune hemolytic anemia, which can also show fragmented cells 5
Hemolysis markers: LDH (elevated), haptoglobin (reduced), indirect bilirubin (elevated) 1
Complete blood count with reticulocyte count to quantify the hemolytic rate 1
Peripheral blood smear review by hematopathology to confirm elliptocytes and quantify fragmentation 4
SDS-PAGE gel electrophoresis of erythrocyte membrane proteins to detect protein 4.1R deficiency or spectrin variants, which confirms the diagnosis definitively 4, 6
Critical Differential Diagnosis Considerations
Hereditary pyropoikilocytosis (HPP) can present identically with elliptocytes, microcytes, and marked fragmentation 7, 4. HPP is essentially a severe variant of HE with enhanced thermal instability of the cytoskeleton 7. If hemolysis is severe, consider thermal instability testing 7.
Pyruvate kinase deficiency would show normal or near-normal red cell morphology without elliptocytes, making it unlikely here 1, 3.
Hereditary spherocytosis would show spherocytes rather than elliptocytes as the predominant abnormal cell type 5, 4.
Management Algorithm
Assess Clinical Severity
Determine if the patient has compensated hemolysis or symptomatic anemia:
Compensated hemolysis (asymptomatic, Hb >10 g/dL): Most HE patients fall into this category and require observation only 6
Symptomatic hemolytic anemia (transfusion-dependent, Hb <8 g/dL, growth impairment in children): Consider splenectomy 3
Monitor for Complications
Screen for these specific complications at diagnosis and periodically:
Cholelithiasis: Obtain abdominal ultrasound, especially after age 10 years, as gallstones occur even without splenectomy 5. Risk is higher with coinheritance of UGT1A1 polymorphisms 5
Iron overload: Check ferritin and transferrin saturation, as iron overload can occur even without transfusions due to ineffective erythropoiesis 3. Consider liver MRI if ferritin is elevated 8
Aplastic crisis: Educate patient about parvovirus B19 risk, which can cause life-threatening red cell aplasia 5
Splenectomy Considerations
Splenectomy is indicated only for:
- Transfusion-dependent anemia
- Growth failure in children
- Severe symptomatic anemia affecting quality of life 3
Post-splenectomy, monitor for:
- Thromboembolic events (lifelong risk) 5
- Continued gallstone formation (risk persists) 5
- Persistent iron overload (can still occur) 3
Critical Pitfalls to Avoid
Do not order enzyme testing (pyruvate kinase assay) when elliptocytes are present - the morphology already establishes the diagnosis as a membrane disorder, not an enzyme deficiency 1, 3, 4
Obtain family history - HE is autosomal dominant, so one parent typically has elliptocytes on their smear, though they may be asymptomatic 6
Check for recent transfusions before any specialized testing - donor red cells can mask the true morphology and protein abnormalities for up to 120 days 3
The degree of microcytosis (cell fragmentation) is the single best predictor of hemolysis severity 2, so quantify the percentage of microcytic cells on the CBC histogram to guide management intensity 2