CASE HISTORY:

A 59 years old gentleman, long standing diabetic, hypertensive and who had undergone PTCA previously, was diagnosed with chronic kidney disease. He gradually became dialysis dependent. This patient was regularly dialysed at our institute and also planned for renal transplant surgery. He was found to be anemic and was routinely evaluated. He was initiated on treatment with recombinant human erythropoietin alpha. Following that, his hemoglobin levels gradually increased, but after few months, his hemoglobin dropped. On further evaluation, his stool occult blood, upper GI endoscopy and colonoscopy were negative, while his peripheral smear showed dimorphic anemia with severe reticulocytopenia. Bone marrow aspiration and cytology was suggestive of PURE RED CELL APLASIA. Parvovirus antibody was also negative. He was treated with steroids and cyclosporine and with multiple transfusions of leucodepleted RBCs, as he was listed for renal transplant. He underwent more than 40 units of RBC transfusions.

In the following period, he underwent renal transplant surgery through a live renal donor. In the post-operative period, he required one unit of transfusion. He was also treated with Hypoxia inducible factor activators. However, his hemoglobin stabilized gradually and was found that his pure red cell aplasia had disappeared. He is now maintaining hemoglobin of 12 g% without the requirement of transfusions or iron supplements.

DISCUSSION:

Pure red cell aplasia (PRCA)  is defined as a normochromic normocytic anemia with severe reticulocytopenia and marked reduction of erythroid precursors from the bone marrow. It can be congenital or acquired. The congenital form is called the Diamond Blackfann anemia. Primary acquired PRCA is generally an antibody mediated condition, however, secondary acquired PRCA is associated with SLE, lymphoproliferative disorders, infections like parvovirus B19, etc.

Patients with chronic kidney disease have anemia, which is essentially due to the reduced erythropoietin produced by the kidneys. We supplement these patients with erythropoietin through the subcutaneous route. These erythropoietin stimulating analogues (ESA) have been implicated in the pathogenesis of PRCA in CKD patients. These analogues have been found to be immunogenic and elicit anti-erythropoeitin antibodies (anti-EPO antibodies). These antibodies suppress the erythroid cell line in the bone marrow without affecting the granulocyte and platelet lineages. There has been extensive literature studying the anti EPO antibodies in the production of PRCA in the CKD patients who are on erythropoietin analogues. Analysis of anti EPO antibodies will help in the diagnosis, apart from excluding the other possibility like drugs, infections, etc.

PRCA is treated with based on its cause. The need for recurrent blood transfusions in these patients are managed appropriately, keeping in mind the iron overload which can happen. In case of drugs causing PRCA, the offending drug has to be stopped. The infections need to be treated. For Parvovirus B19 infections, IVIg has to be administered. On the exclusion of the above, and suspicion of anti EPO antibodies causing PRCA, immunosuppression is advised to the patients including steroid and non-steroidal agents. The usual regimen includes prednisone and cyclosporine, which effectively treat the PRCA.

In our patient, he was extensively evaluated for the cause of PRCA and was concluded that he had developed it due to the administration of subcutaneous erythropoietin analogues based on the exclusion of other causes. He was given multiple leucodepleted RBC transfusions along with steroids and cyclosporine. This patient, then underwent renal transplant, following which his need for blood transfusions, steroids and cyclosporine were reduced. The transplanted kidney has reduced his needs for erythropoietin administration, by taking over its production, which explains his sustaining hemoglobin levels post renal transplant.

Dr. Balaji Kirushnan
Consultant Nephrologist
Nephrology Department, Kauvery Hospital, Chennai