ANEMIA IN CROHNS-DISEASE - IMPORTANCE OF INADEQUATE ERYTHROPOIETIN PRODUCTION AND IRON-DEFICIENCY

Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress er ythropoietin production. This study was performed to investigate the i mportance of iron status, inflammatory activity, and endogenous erythr opoietin concentrations for the development of anemia in Crohn's disea se. In 49 consecutive patients with Crohn's disease, hemoglobin, infla mmatory activity (Crohn's disease activity index, C-reactive protein, alpha(1)-acid glycoprotein), iron status (serum iron, transferrin, tra nsferrin saturation, ferritin), and serum erythropoietin levels were s tudied. Anemic (Hb < 12.0 g/dl; N = 16) vs nonanemic patients (Hb grea ter than or equal to 12 g/dl; N = 33) showed reduced iron compartments leg, ferritin 28.7 +/- 12.9 mu g/liter vs 63.2 +/- 15.0 mu g/liter, t ransferrin saturation 6.2 +/- 1.4% vs 11.5 +/- 1.3%, P < 0.01) but no differences in inflammatory activity. An inverse correlation between e rythropoietin and hemoglobin concentrations was found (r = -0.62; P < 0.001), but the increase in erythropoietin levels was inadequate to th e degree of anemia. There was no correlation between erythropoietin an d interleukin-6 serum levels. Four of five anemic patients with hemogl obin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml N aCl, weekly, intravenously). Two of them additionally received recombi nant human erythropoietin (150 units/kg, 3x weekly, subcutaneously). A fter five weeks all patients had a marked increase in hemoglobin. Howe ver, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only. No side effects were seen. Our data demonstrate that inadequate erythropoietin production and iron deficiency are pathogenetic factors of anemia in Crohn's disease. The therapeutic management using recombinant human er ythropoietin and parenteral iron is reasonable and effective.