What does the presence of bite or blister cells on a Complete Blood Count (CBC) indicate?

Bite and Blister Cells on CBC

Bite cells (also called degmacytes) and blister cells are red blood cell abnormalities seen on peripheral blood smear that indicate oxidative hemolysis, most commonly from glucose-6-phosphate dehydrogenase (G6PD) deficiency or drug-induced oxidative injury. 1, 2, 3

Morphologic Characteristics

• Bite cells appear as poikilocytes with one or more semicircular portions removed from the cell margin, giving the appearance that a piece has been "bitten out" of the red blood cell 2, 3
• Blister cells represent an earlier stage where Heinz bodies (denatured hemoglobin) create a blister-like appearance before splenic removal creates the bite cell 3
• These cells are best identified on Wright-stained peripheral blood smears during active hemolysis 2, 3

Clinical Significance and Pathophysiology

• Bite cells form when splenic macrophages remove Heinz bodies (oxidatively denatured hemoglobin) from circulating red blood cells, leaving the characteristic semicircular defect 2, 3
• The presence of bite cells indicates ongoing oxidative stress overwhelming the red blood cell's reducing capacity, particularly in G6PD-deficient cells that lack adequate NADPH production 1, 4
• Oxidative denaturation of hemoglobin releases hemin into the RBC membrane, which further oxidizes membrane proteins and reduces cell deformability 4

Diagnostic Workup When Bite Cells Are Identified

Immediate laboratory evaluation should include:

• Complete blood count with reticulocyte count to assess degree of hemolysis and bone marrow response 5, 6
• Peripheral blood smear examination for quantification of bite cells (typically 5.5-13.6% during active hemolysis), blister cells, spherocytes, and Heinz bodies 3, 7
• Lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, and direct antiglobulin test (Coombs) to confirm hemolysis and exclude immune-mediated causes 5, 6
• G6PD enzyme activity assay to confirm deficiency (note: may be falsely normal during acute hemolysis due to young reticulocytes with higher enzyme levels; repeat 2-3 months after resolution) 1, 7

Additional targeted testing:

• Comprehensive medication review and toxicology screen for oxidant drugs including dapsone, phenazopyridine, nitrofurantoin, primaquine, sulfonamides, and methylene blue 5, 2, 3
• Methemoglobin level if cyanosis or chocolate-brown blood is present 5
• Urinalysis for hemoglobinuria (reddish discoloration without RBCs on microscopy) 7
• Assessment for infectious triggers, particularly in G6PD deficiency where infection can precipitate hemolytic crisis 1, 7

Common Causes

G6PD deficiency is the most common enzymatic cause, particularly in African-American, Mediterranean, and Asian populations 1, 7, 4

Oxidant drug exposure including phenazopyridine, dapsone, nitrofurantoin, sulfonamides, and antimalarials 2, 3

Severe oxidative stress states such as diabetic ketoacidosis, sepsis, or significant inflammatory burden 1, 7

Management Algorithm

Grade 1-2 (Hemoglobin <LLN to 8.0 g/dL):

• Immediately discontinue all potentially offending medications 5, 3
• Monitor hemoglobin, reticulocyte count, and LDH weekly 5, 6
• Provide supportive care with adequate hydration 5
• Consider prednisone 0.5-1 mg/kg/day if hemolysis is severe or progressive 5, 6

Grade 3 (Hemoglobin <8.0 g/dL with transfusion indicated):

• Permanently discontinue causative agent 5
• Hematology consultation 5
• Consider hospital admission based on clinical status and rate of hemoglobin decline 5
• Administer prednisone 1-2 mg/kg/day (oral or IV) 5
• Transfuse RBCs only to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients; avoid over-transfusion 5, 6
• Supplement with folic acid 1 mg daily to support erythropoiesis 5

Grade 4 (Life-threatening consequences):

• Immediate hospital admission 5
• Urgent hematology consultation 5
• IV methylprednisolone 1-2 mg/kg/day 5
• Aggressive supportive care including renal protection with hydration to prevent hemoglobin-induced acute tubular necrosis 7

Critical Pitfalls to Avoid

• Do not dismiss bite cells as artifact—their presence always indicates pathologic oxidative hemolysis requiring investigation 2, 3
• Do not test G6PD levels during acute hemolysis—young reticulocytes have higher enzyme activity and can yield false-negative results; repeat testing 2-3 months after resolution 1
• Do not rely solely on biochemical markers—bite cell percentage (5.5-13.6%) correlates better with hemolysis severity than traditional markers like LDH or haptoglobin, which may not be consistently elevated 3
• Do not continue oxidant medications—withdrawal of the offending drug results in improvement of hemolytic anemia and disappearance of bite cells within days to weeks 2, 3
• Do not overlook rhabdomyolysis—severe oxidative stress in G6PD deficiency can rarely cause concomitant muscle injury, particularly with inflammatory triggers 1

Expected Clinical Course

• Bite cells typically disappear from peripheral blood within days to weeks after removal of the oxidant trigger 2, 3
• Reticulocytosis peaks 5-7 days after hemolysis onset and normalizes as hemoglobin recovers 3
• Close correlation exists between hematocrit reduction, reticulocyte response, and bite cell percentage during active hemolysis 3