Hereditary Hemolytic Anemia (Blood Dyscrasia)
The most likely cause of this patient's anemia is a hereditary hemolytic disorder—specifically a blood dyscrasia such as hereditary spherocytosis, pyruvate kinase deficiency, or thalassemia—given the combination of family history of anemia, splenomegaly, and evidence of chronic hemolysis in a young patient. 1
Clinical Reasoning
The key diagnostic features pointing toward hereditary hemolytic anemia include:
- Family history of anemia strongly suggests an inherited disorder rather than acquired causes 1
- Palpable splenomegaly indicates chronic hemolysis with splenic sequestration of abnormal red blood cells 1
- Young age (17 years) with no prior medical history makes chronic disease or malignancy less likely
- Pale conjunctiva reflects the anemia itself, which in hereditary hemolytic disorders results from accelerated red cell destruction 1
Differential Diagnosis Analysis
Why Blood Dyscrasia (Answer A) is Correct:
Hereditary hemolytic anemias present with chronic hemolysis features including increased reticulocyte count, elevated LDH, reduced haptoglobin, and elevated bilirubin. 1 The splenomegaly occurs because younger defective erythrocytes are selectively sequestered by the spleen in conditions like pyruvate kinase deficiency and membrane disorders. 1
The family history is particularly telling—hereditary hemolytic diseases including red cell enzyme deficiencies, membrane disorders, and hemoglobinopathies are inherited conditions that commonly present with positive family history. 1, 2
Why Other Options are Less Likely:
Iron deficiency (Answer B): While iron deficiency can cause pale conjunctiva, it does not typically cause splenomegaly. 1 Iron deficiency anemia results from dietary insufficiency, GI blood loss, or malabsorption—none of which explain the splenomegaly or family history. 1 Additionally, serum ferritin would be low (<12 μg/dL) in iron deficiency, whereas in hereditary hemolytic anemias, iron parameters may actually be increased disproportionally even without transfusions. 1
Malignancy (Answer C): While hematologic malignancies can cause anemia and splenomegaly, they are uncommon in a 17-year-old with no prior medical history and would not explain the family history of anemia. 3
Vitamin deficiency (Answer D): Megaloblastic anemias from B12 or folate deficiency cause macrocytic anemia, not the presentation seen here, and do not typically cause splenomegaly or have familial patterns. 3
Diagnostic Workup Needed
The diagnostic approach should exclude immune-mediated hemolysis, then evaluate for specific hereditary disorders: 1
- Complete blood count with reticulocyte count (expect elevated reticulocytes indicating hemolysis) 1
- Peripheral blood smear to assess red cell morphology (spherocytes suggest hereditary spherocytosis; relatively normal morphology with some anisocytosis/poikilocytosis suggests enzyme deficiency) 1
- Hemolysis markers: LDH (elevated), haptoglobin (reduced), indirect bilirubin (elevated) 1
- Direct antiglobulin test (Coombs) to exclude autoimmune hemolytic anemia 1, 3
- Hemoglobin electrophoresis to evaluate for thalassemia or hemoglobinopathies 2, 4
- Red cell enzyme assays (particularly pyruvate kinase) if other tests are unrevealing 1
Important Clinical Pitfalls
Do not assume dietary iron deficiency or dismiss the family history. 1 A positive family history of anemia should prompt investigation for hereditary disorders, and the presence of splenomegaly essentially rules out simple nutritional deficiency. 1
Reticulocyte count may not be as elevated as expected in hereditary hemolytic anemias before splenectomy because younger defective cells are preferentially sequestered in the spleen, creating a falsely reassuring reticulocyte response. 1