Pure Red Cell Aplasia

Pure red cell aplasia (PRCA) is isolated failure of erythropoiesis, with severe anaemia, reticulocytopenia and absent marrow erythroblasts (under 5%).

• Acquired causes: thymoma (5 to 10%), large granular lymphocyte leukaemia, CLL and lymphoproliferative disease, autoimmune disease (SLE, rheumatoid arthritis), parvovirus B19 (chronic in immunodeficiency), drugs (phenytoin, azathioprine, isoniazid, sulfonamides, ribavirin), erythropoietin antibodies (epoetin associated), ABO incompatible transplant, pregnancy, idiopathic.
• Congenital form is Diamond Blackfan anaemia (separate article).
• Transient erythroblastopenia of childhood is self limiting.
• Mechanism: antibody or T cell mediated suppression of erythroid progenitors.

• Insidious pallor, fatigue, dyspnoea, tachycardia, high output signs.
• No bleeding or infection (white cells and platelets normal).
• Features of the underlying cause: myasthenia gravis, cough or chest signs in thymoma, lymphadenopathy, splenomegaly in LGL leukaemia.

• Normocytic normochromic anaemia, reticulocytes under 1% (under 10 x 10^9/L), normal white count and platelets.
• Bone marrow: normal cellularity with absent erythroid precursors, occasional giant proerythroblasts (parvovirus).
• Parvovirus B19 PCR in blood and marrow (serology unreliable in immunosuppressed).
• Chest CT for thymoma, flow cytometry for LGL, T cell receptor gene rearrangement, ANA, anti dsDNA, HIV, hepatitis, drug history.
• Anti erythropoietin antibodies in patients on ESAs (stop ESA).
• Cytogenetics to exclude MDS.

• Remove the cause: stop drugs, ESA; thymectomy for thymoma (response in about 30%); treat lymphoproliferative disease.
• Parvovirus: IVIG 0.4 g/kg daily for 5 days (or 1 g/kg for 2 days), repeat for relapses; reduce immunosuppression.
• Immunosuppression for idiopathic or autoimmune PRCA: ciclosporin 5 to 6 mg/kg/day (trough 150 to 250 µg/L), response in 65 to 75%, first line; prednisolone 1 mg/kg daily for 4 weeks (response about 40%); cyclophosphamide 50 to 100 mg daily; antithymocyte globulin 40 mg/kg/day for 4 days; rituximab 375 mg/m2 weekly for 4 doses; alemtuzumab.
• Eltrombopag has been used in refractory cases. Danazol, luspatercept in selected patients.
• Supportive transfusion with leucodepleted blood; iron chelation if overloaded.
• Monitor for relapse during taper (common).