Complete Blood Count Findings in Hydroxyurea Toxicity
Hydroxyurea toxicity manifests on CBC as pancytopenia—specifically anemia (hemoglobin <10 g/dL), neutropenia (absolute neutrophil count <1.0 × 10⁹/L), and thrombocytopenia (platelet count <100 × 10⁹/L)—with macrocytosis being a characteristic finding even at therapeutic doses. 1, 2, 3
Primary Hematologic Abnormalities
Anemia
- Hemoglobin drops below 10 g/dL, which represents the mandatory discontinuation threshold per NCCN and European LeukemiaNet guidelines 2, 3
- The anemia is typically megaloblastic in nature with macrocytosis (elevated MCV) 4
- A linear increase in mean red cell volume occurs, with the entire normocyte population replaced by abnormally large erythrocytes within 150 days of continuous therapy 4
- Hemolytic anemia can occur as a less common manifestation, requiring assessment of LDH, haptoglobin, reticulocyte count, bilirubin, and Coombs test to differentiate from pure marrow suppression 2, 5
Neutropenia
- Absolute neutrophil count falls below 1.0 × 10⁹/L in toxicity, meeting criteria for immediate dose reduction or discontinuation 2, 3
- This represents one of the three cardinal cytopenias defining hydroxyurea intolerance 6
Thrombocytopenia
- Platelet count drops below 100 × 10⁹/L (for polycythemia vera) or below 50 × 10⁹/L (for primary myelofibrosis) at the lowest effective dose 2, 6
- Thrombocytopenia is specifically recognized as a dose-limiting toxicity requiring discontinuation 6, 7
Characteristic Morphologic Changes
Macrocytosis (Even at Therapeutic Doses)
- Macrocytosis develops universally during hydroxyurea therapy and should not be confused with vitamin B12 or folate deficiency 4
- The bone marrow shows megaloblastic morphology with increased iron stores and sideroblasts, compatible with ineffective erythropoiesis 4
- Serum folate and cobalamin levels remain normal despite the megaloblastic appearance 4
Reticulocyte Response
- Reticulocyte count typically declines as the maximum tolerated dose is approached, signaling impending marrow suppression 2
- In sickle cell disease monitoring, a declining reticulocyte trend indicates dose escalation should stop 2
Critical Monitoring Parameters
Frequency of CBC Monitoring
- Weekly CBC until stable dose achieved, then monthly for psoriasis patients 1
- Every 2–4 weeks during dose titration, then every 1–3 months on stable dose for myeloproliferative disorders 3
- Every 4 weeks while adjusting doses in sickle cell disease, then every 8–12 weeks after stabilization 2
Additional Laboratory Findings
- Bone marrow cellularity decreases with reduced maturing granulocytes 8
- Increased bone marrow iron stores and sideroblasts reflect ineffective erythropoiesis 4
- Elevations in serum uric acid, BUN, and creatinine may accompany hematologic toxicity 1, 7
Management Algorithm When Toxicity Detected
Immediate discontinuation is mandatory when any of the following thresholds are met 2, 3:
- Hemoglobin <10 g/dL
- Absolute neutrophil count <1.0 × 10⁹/L
- Platelet count <100 × 10⁹/L (polycythemia vera) or <50 × 10⁹/L (primary myelofibrosis)
After hematologic recovery (hemoglobin >10 g/dL and resolution of other cytopenias), hydroxyurea may be restarted at a 25–50% lower dose than the dose that caused suppression 2
Bone marrow suppression is reversible, typically resolving within 2 weeks of temporary discontinuation in sickle cell disease patients 2
Common Pitfall
Do not assume all hydroxyurea-induced anemia is purely from marrow suppression—hemolytic anemia can occur and requires specific evaluation with hemolysis markers (LDH, haptoglobin, indirect bilirubin, Coombs test) to guide appropriate management 2, 5. The presence of macrocytosis alone does not exclude concurrent hemolysis.