Keywords
antiepileptic therapy - carbamazepine - pure red cell aplasia
Introduction
Pure red cell aplasia (PRCA) is a relatively rare disease. Acquired PRCA is usually
transient when compared with the congenital variety. Acquired PRCA can be associated
with malnutrition, drugs, toxins, and infections. Carbamazepine (C15H12N2O) is a tricyclic compound that is most efficient against partial seizure with or
without secondary generalization. Carbamazepine is known to cause a variety of hematologic
abnormalities.
Case
A 32-year-old unmarried woman was admitted with fatigue for 4 months. She denied history
of fever, weight loss, loss of appetite, bleeding manifestations, high-risk behavior,
had no sick contacts, and had no history of addictions. She had been on carbamazepine
therapy for 4 years (200 mg twice daily) for seizure disorder. She had severe pallor
but had no lymphadenopathy or hepatosplenomegaly.
Hemoglobin was 4.5 g/dL (normocytic and normochromic), total leucocyte count 6,500/mL
with 64% neutrophils, and platelet count 3,56,000/µL. The blood chemistry was normal.
Peripheral smear showed predominantly normocytic normochromic red blood cells with
scattered microcytes and macrocytes ([Fig. 1]). White blood cells and platelets were adequate. Absolute reticulocyte count was
0.3% and reticulocyte index was 0.13. Stool occult blood was negative and had no ova
or cyst. Iron studies were normal (serum iron was 164 µg/dL, total iron-binding capacity
294 µg/dL, and serum ferritin 401 ng/mL). Human immunodeficiency virus (HIV), hepatitis
B, and hepatitis C serologies were negative. Serum vitamin B12 and folic acid were normal. Bone marrow trephine biopsy showed marked erythroid hypoplasia
with normal myeloid and megakaryocyte maturation. There was no marrow fibrosis on
reticulin staining, and immunohistochemistry for E-cadherin for identifying the erythroid
lineage showed positivity in few cells confirming marked erythroid hypoplasia ([Fig. 2]). The patient was diagnosed to have PRCA as there was normocytic normochromic anemia,
with a very low reticulocyte count, marked erythroid hypoplasia, without evidence
of hemolysis and normal leucocyte and platelet counts. The Naranjo adverse drug reactions
probability score was 10, suggesting that carbamazepine was the probable cause for
PRCA. Carbamazepine was discontinued and patient was started on levetiracetam 500
mg three times daily for seizure. She also received packed cell transfusions. When
reviewed after 3 months, she was asymptomatic and hemoglobin was 11.5 g/dL.
Fig. 1 Peripheral smear showing predominantly normocytic normochromic red blood cells with
scattered microcytes and macrocytes (hematoxylin and eosin staining).
Fig. 2 (A) Bone marrow trephine biopsy showing marked erythroid hypoplasia with normal myeloid
and megakaryocyte maturation and mild lymphocytic infiltration. (B) Reticulin showing no fibrosis in the marrow. (C) Immunohistochemistry for E-cadherin showing positivity in very few cells. (D) Immunohistochemistry for CD45 highlighting the mild lymphocytic infiltration (hematoxylin
and eosin staining).
Discussion
Pure red cell aplasia is a rare disease and may be congenital or acquired. Severe
normocytic anemia, reticulocytopenia, and absence of erythroblasts from an otherwise
normal bone marrow should raise the suspicion of PRCA.[1] Acquired PRCA is usually transient in nature in contrast to the congenital variety.
Acquired PRCA can be associated with drugs, toxins, and infectious agents or from
unknown causes.
Several mechanisms are postulated in the pathogenesis of drug-induced PRCA, including
toxic interference by drugs with the metabolism of nucleated red cells, immunologically
mediated reaction with antibodies formed against red cell precursors, and specific
inhibitory effect on DNA synthesis probably at the step of deoxyriboside formation.[2] Drug-induced PRCA is reversible after discontinuation of the offending drug.
Antiepileptics such as diphenylhydantoin, sodium valproate, and carbamazepine were
previously reported to be associated with PRCA.[3]
[4]
[5] Drugs can be responsible for various red blood cell–related syndromes, including
hemolytic anemia, methemoglobinemia, PRCA, sideroblastic anemia, megaloblastic anemia,
and polycythemia.
Pure red cell aplasia is an uncommon complication of carbamazepine therapy. PRCA after
carbamazepine therapy was previously reported in a 2-year-old boy after 6 months at
a daily dose of 10 mg/kg. It resolved following discontinuation of carbamazepine.[4] Few more cases of carbamazepine-induced PRCA were reported previously in the literature.[6]
[7]
[8]
[9] We present this case to make the readers aware of an extremely rare complication
related to carbamazepine, which is reversible with discontinuation of the drug.
