Red cell aplasia

Roberts, H.J. 1990. Pentachlorophenol-associated aplastic anemia, red cell aplasia, leukemia and other blood disorders. Jour. Florida Medic. Assoc. 77 86-90. 

Kharagjitsingh, A.V. et al., Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated antibodies, and pure red cell aplasia in dialysis patients, Kidney Int., 68, 1215, 2005. 

Pure red cell aplasia (PRCA) PRCA has been reported in a limited number of patients exposed to epoetin alfa. This has been reported predominantly in patients with CRF. Evaluate any patient with loss of response to epoetin alfa for the etiology of loss of effect. Discontinue epoetin alfa in any patient with evidence of PRCA and evaluate the patient for the presence of binding and neutralizing antibodies to epoetin alfa, native erythropoietin, and any other recombinant erythropoietin administered to the patient. In patients with PRCA secondary to neutralizing antibodies to erythropoietin, do not administer epoetin alfa, and do not switch such patients to another product as anti-erythropoietin antibodies cross-react with other erythropoietins. 

An inverse log-linear relationship has been found between hematocrit and plasma erythropoietin in anemic patients with normal renal function. Patients with chronic renal failure have inappropriately low erythropoietin levels for their degree of anemia [10]. The severity of anemia correlates with the extent of renal dysfunction. Intravenous or subcutaneous recombinant human erythropoietin given three times a week is the treatment of choice. Some patients seem to do well on only one injection per week. One version of erythropoietin, Epocrit, marketed outside the United States, has been associated with pure red cell aplasia. 

Allergic reactions to ESAs have been infrequent. There have been a small number of cases of pure red cell aplasia (PRCA) accompanied by neutralizing antibodies to erythropoietin. PRCA was most commonly seen in dialysis patients treated subcutaneously for a long period with a particular form of epoetin alfa (Eprex with a polysorbate 80 stabilizer rather than human serum albumin) that is not available in the USA. After regulatory agencies required that Eprex be administered intravenously rather than subcutaneously, the rate of ESA-associated PRCA diminished. However, rare cases have still been seen with all ESAs administered subcutaneously for long periods to patients with chronic kidney disease. 

Epoetin alfa Agonist of erythropoietin receptors expressed by red cell progenitors Stimulates erythroid proliferation and differentiation, and induces the release of reticulocytes from the bone marrow Treatment of anemia, especially anemia associated with chronic renal failure, HIV infection, cancer, and prematurity prevention of the need for transfusion in patients undergoing certain types of elective surgery IV or SC administration 1-3 times per week Toxicity Hypertension, thrombotic complications, and, very rarely, pure red cell aplasia to reduce the risk of serious CV events, hemoglobin levels should be maintained < 12 g/dL... 

McKoy JM et al Epoetin-associated pure red cell aplasia Past, present, and future considerations. Transfusion 2008 48 1754. [PMID 18482185]... 

Anecdotal exposure to pentachlorophenol has been associated with aplastic anaemia and/or red-cell aplasia (Roberts, 1983). Thirteen cases of industrial, home and accidental pentachlorophenol exposure in 11 men and two women having aplastic anaemia, pure red cell aplasia and associated disorders were reported. Exposure levels were not known except for one patient, who had concentrations in the serum of 250 ng/mL and in bone marrow of 330 ng/mL (Roberts, 1990). 

The most dangerous adverse reaction of sulfonylureas is agranulocytosis. Aplastic anemia (79), red cell aplasia (80), pure white cell aplasia (81), bone marrow aplasia, and hemolytic anemia have been described during treatment with chlorpropamide (82), glibenclamide (83), or tolbutamide (84). 

Leuprolide acetate has been reported to cause normochromic normocytic anemia in patients with benign prostatic hyperplasia (37). The anemia is usually transient, and the hemoglobin returns to baseline 6 months after stopping androgen suppression. There is a single case report of more serious red cell aplasia in a patient receiving gonadorelin, with resolution after treatment was withdrawn (38). 

Maeda H, Arai Y, Aoki Y, Okubo K, Okada T, Ueda Y. Leuprolide causes pure red cell aplasia. J Urol 1998 160(2) 501. 

Abbreviations EPO erythropoietin GH growth hormone PRCA pure red cell aplasia RIA radioimmunoassay SC subcutaneous TNF tumor necrosis factor. 

Boven K, Knight J, Bader F, Rossert J, Eckardt KU, Casadevall N Epoetin associated pure red cell aplasia in patients with chronic kidney disease solving the mystery. Nephrol. Dial. Transplant. (2005) 20 (Suppl 3) iii33-iii40. 

Bunn HF. Drug-induced autoimmune red-cell aplasia. N Engl J Med 2002 346 522-3. 

Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-Dupont P, Michaud P, Papo T, Ugo V,Teyssandier I, Varet B, Mayeux P. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med 2002 346 469-75. 

Lim LC. Acquired red cell aplasia in association with the use of recombinant erythropoietin in chronic renal failure. Hematology 2005 10 255-9. 

Other general effects include cholestasis, hepatocellular toxicity, thrombocytopenia, neutropenia, red cell aplasia, and haemolytic anaemia. Ovulation may be reduced or delayed (reversibly). 

Ide, T., Sata, M., Nouno, R., Yamashita, F., Nakano, H., Tanikawa, K. Clinical evaluation of four cases of acute viral hepatitis complicated by pure red cell aplasia. Amer. X Gastroenterol. 1994 89 257-262... 

Creemers GJ, van Boven WP, Lowenberg B, van der Heul C. Azathioprine-associated pure red cell aplasia. J Intern Med 1993 233(l) 85-7. 

Pruijt JF, Haanen JB, Hollander AA, den Ottolander GJ. Azathioprine-induced pure red-cell aplasia. Nephrol Dial Transplant 1996 ll(7) 1371-3. 

Cavanzo FJ, Garcia CF, Botero RC. Chronic cholestasis, paucity of bile ducts, red cell aplasia, and the Stevens-Johnson syndrome. An ampicillin-associated case. Gastroenterology 1990 99(3) 854-6. 

Some 15 cases of thrombocytopenia, reversible after withdrawal of carbamazepine, have been published (SED-13, 147) (41,42). There have also been single case reports of reticulocytosis (SED-13,147) (43), leukopenia with thrombocytopenia with Henoch-Schonlein purpura (SEDA-18,63), hemolytic anemia, and pure red cell aplasia (SED-13,147) (44). 

Buitendag DJ. Pure red-cell aplasia associated with carbamazepine. A case report. S Afr Med J 1990 78(4) 214-15. 

Worldwide, 112 cases of pure red cell aplasia have been reported after subcutaneous administration of epoetin alfa (especially Eprex) in patients with chronic renal insufficiency. In these patients, neutralizing anti-eiythropoietin antibodies were detected (82-84) these antibodies cross-react with all other erythropoietin products. This adverse... 

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