Recovery from aplastic anaemia after institution of haemodialysis

Katsuko Shiraya1, Yoshifumi Ubara1, Hideyuki Katori1, Yoshio Matsushita1, Tetsuo Tagami1, Masafumi Yokota1, Akiko Kitamura1, Fumi Takemoto1, Shigeko Hara1, Yoshitomo Mutoh2 and Akira Yamada1

1 Kidney Centre 2 Department of Hematology, Toranomon Hospital, Japan

Sir,

Recently, administration of recombinant human erythropoietin (rHuEpo) has been reported to be an effective treatment for patients with aplastic anaemia (AA) [1]. We report here a primary AA patient complicated with end-stage renal disease (ESRD). Although he did not respond to high dose administration of rHuEpo before introduction to haemodialysis (HD), he showed marked improvement in erythropoietic cell-line as well as megakaryocytes with administration of a low dose of rHuEpo after initiation of HD.

Case

A 66-year-old male had a history of exposure to trichloro-ethylene from 5 to 35 years of age. At the age of 50 (1982), he was diagnosed as having diabetes mellitus. The following year, he visited a clinic with a complaint of haemorrhagic diathesis, and AA was diagnosed. Until then, any drugs with the potential of bone marrow (BM) suppression were not administered. Oral oxymetholene (30 mg/day) improved his anaemia. In 1992, he developed diabetic nephropathy. In 1994, oral administration of oxymetholone had to be stopped because of adverse effects. In November 1995 it was noted that peripheral red blood cells were markedly decreased. High doses of intravenous rHuEpo (12 000 U/week) were administered for 2 months, with no desirable responses. On March 14 1996, he was admitted to our hospital complaining of worsened renal function. Laboratory findings demonstrated severe pancytopenia; red blood cell (RBC) count was 189x104/µl, haematocrit was 16.4%, white blood cell count was 1700/µl, platelet count was 1.6x104/µl. Serum level of creatinine (4.3 mg/dl) and urea nitrogen (67 mg/dl) were increased, total bilirubin was in the normal range (0.4 mg/dl). Serum iron (188 µg/dl) and ferritin (510 µg/l) were increased, haptoglobin (13.6 mg/dl) was decreased. Erythropoietin concentration was in the normal range (18.9 mU/ml). Massive proteinuria (3 g/day) was noted, 24-h creatinine clearance test was 10.5 ml/min. BM was markedly hypoplastic (nucleated cell count: (NCC) 2.35x104/µl), but no cytological abnormality was noted.

Diagnosis as AA complicated with ESRD was made. Oral administration of metenolone acetate (15 mg/day) showed no effect, and the patient needed RBC transfusion of 400 ml weekly. Regular HD twice a week was instituted and intravenous rHuEpo (6000 U/week) administration was started on May 29. After 2 months, a gradual improvement in the peripheral blood cell count was observed. Two months thereafter, demand for RBC transfusion significantly decreased. In November 1996, HD session was increased to 3 times a week and rHuEpo was increased to 9000 U/week. After May 1997, RBC transfusion was no longer necessary (Figure 1Go). Two years after the start of HD and rHuEpo therapy, BM examination proved normocellular marrow (NCC 16.7x104/µl) with slight erythroid hyperplasia, and significantly increased megakaryocytes (16/mm2).



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Fig. 1. Clinical course of the patient.

 

Comment.

In this case, rHuEpo induced an increase in both erythropoietic cell-line and megakaryocytes. Recently, rHuEpo therapy was shown to stimulate megakaryopoiesis [2], and in a few patients with AA treated with rHuEpo, significant trilineage responses are reported [3,4]. According to Callen et al. in more than 80% of cases of azotemic patients, BM was hypercellular and no patient was found to have aplastic BM [5]. Although, in our case, the finding of BM examination was compatible with AA, ESRD seems to have modified the course of AA, because haematological data worsened in parallel with the deterioration of renal function. Anaemia in patients with ESRD is induced by factors such as deficit in erythropoietin production, haemolysis, malnutrition and so on [2,5,6]. Also, Lamperi et al. reported that uraemic toxins may reduce the metabolic activity of BM cells [6]. In fact in the present case, although administration of rHuEpo 12 000 U/week was ineffective before institution of HD, rapid regeneration of BM occurred with administration of rHuEpo only 6000 U/week after institution of HD. The clinical course of our case suggests a possible relationship between the response of BM to rHuEpo and the removal of uraemic toxins by HD.

References

  1. Yoshida Y, Anzai N, Kawabata H, Kohsaka Y, Okuma M. Serial changes in endogenous erythropoietin levels in patients with myelodysplastic syndromes and aplastic anemia undergoing erythropoietin treatment. Ann Hematol1993; 66: 175–180[ISI][Medline]
  2. Horina JH, Schmid CR, Roob JM et al. Bone marrow changes following treatment of renal anemia with erythropoietin. Kidney Int1991; 40: 917–922[ISI][Medline]
  3. Bernell P. Aplastic anemia with a trilineage resonse to erythropoietin therapy. J Intern Med1996; 239: 79–81[ISI][Medline]
  4. Nakamura N, Kubo K, Komatsu Y et al. A case of aplastic anemia combined with chronic renal failure improved after administration of high-dose recombinant human erythropoietin. Touseki-Kaishi1992; 25: 1271–1277
  5. Callen IR, Limarzi LR. Blood and bone marrow studies in renal disease. Am J Clin Path1950; 20: 3–23[ISI][Medline]
  6. Lamperi S, Bandiani G, Fiorio P, Muttini P, Scaringi G. Effects of some substances retained in uremia on erythropoiesis: the effect on bone marrow cell cultures. Nephron1974; 13: 278–287[ISI][Medline]




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