What is the next step in diagnosis for a patient with a picture smear showing spherocytes and tear drop cells, such as hereditary spherocytosis (HGB), considering tests like Osmotic Fragility, Bone Marrow examination, or Hemoglobin (HGB) electrophoresis?

Diagnostic Approach for Peripheral Blood Smear with Spherocytes and Tear Drop Cells

The osmotic fragility test is the most appropriate next diagnostic step for a patient with spherocytes and tear drop cells on peripheral blood smear, as it can specifically confirm hereditary spherocytosis which is strongly suggested by the presence of spherocytes. 1, 2

Understanding the Peripheral Blood Smear Findings

• Spherocytes are characteristic of hereditary spherocytosis (HS), the most common inherited hemolytic anemia, and represent red blood cells that have lost their biconcave shape due to membrane defects 1
• Tear drop cells (dacryocytes) can be seen in various conditions including myelofibrosis, myelodysplastic syndromes, and occasionally in hemolytic anemias 3
• The combination of these findings strongly suggests a red cell membrane disorder, with hereditary spherocytosis being the most likely diagnosis 2

Diagnostic Algorithm

First-line Testing: Osmotic Fragility Test

• Osmotic fragility testing is highly specific for diagnosing hereditary spherocytosis with sensitivity of 93.85% and specificity of 98.38% when properly performed 2
• The test measures the resistance of red blood cells to hemolysis in solutions of decreasing osmolarity, which is characteristically decreased in HS 4
• Modern flow cytometric osmotic fragility tests (FC-OFT) provide rapid, reproducible results requiring smaller blood volumes than traditional methods 1, 4
• EDTA is the preferred anticoagulant for osmotic fragility testing, and incubation at 37°C for 24 hours may increase diagnostic capability 4

Alternative Diagnostic Options

Hemoglobin Electrophoresis (Option A)

• Not the first-line test for suspected hereditary spherocytosis 3
• More appropriate for hemoglobinopathies (sickle cell disease, thalassemias) which typically present with different morphological findings 3
• Would not directly confirm the membrane defect suggested by spherocytes 2

Bone Marrow Examination (Option B)

• Not indicated as initial test for suspected hereditary spherocytosis 3
• More appropriate when:
  • Myelodysplastic syndrome is suspected (which could explain tear drop cells but not spherocytes) 3
  • Bone marrow infiltrative disorders are the primary concern 3
  • There are additional findings suggesting a primary bone marrow disorder 3

Supporting Laboratory Findings in Hereditary Spherocytosis

• Increased mean corpuscular hemoglobin concentration (MCHC) >34.5 g/dL (sensitivity 81%, specificity 98.9%) 5
• Increased red cell distribution width (RDW) >14.5% (sensitivity 81%, specificity 98.9%) 5
• Reticulocytosis reflecting compensatory erythropoiesis 3
• Evidence of hemolysis (elevated indirect bilirubin, decreased haptoglobin) 3

Common Pitfalls to Avoid

• Relying solely on peripheral blood morphology without confirmatory testing can lead to misdiagnosis 6
• Using heparin as anticoagulant for osmotic fragility testing reduces test accuracy 4
• Failing to consider that approximately 1.1% of the general population may have increased osmotic fragility without clinical disease (possible carriers of spherocytosis trait) 6
• Not recognizing that spherocytes may also be seen in autoimmune hemolytic anemia, which requires different diagnostic workup (direct antiglobulin test) 3

The osmotic fragility test remains the gold standard for confirming hereditary spherocytosis when spherocytes are seen on peripheral blood smear, making it the most appropriate next diagnostic step in this clinical scenario 1, 2, 4.