Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha

Treatment of chronic hepatitis C with interferon (IFN)-alpha often has hematotoxic effects. We evaluated the effects of acute vs. chronic and standard vs. pegylated IFN-alpha on hematopoiesis.

We studied hematopoiesis in 46 patients with chronic hepatitis C receiving single high-dose IN-Falpha2b followed by daily dose standard or weekly pegylated IFN before combination antiviral therapy.

Single high-dose therapy resulted in a significant drop in hemoglobin (HB), leukocytes, and platelet count. Although platelets, stimulated by a significant increase in thrombopoietin (TPO), and leukocytes recovered quickly, HB remained below baseline for 7 days. Daily standard or weekly pegylated IFN-alpha leads to a more pronounced drop in all 3 lineages with concomitant increases in TPO and erythropoietin (EPO). No difference was observed between standard and pegylated IFN, except for HB, which fell more during pegylated IFN therapy. Consecutive combination antiviral therapy aggravated the anemia but not the drop in leukocytes or thrombocytes.

The drop in all 3 hematopoietic lineages through IFN-alpha treatment, high-dose standard, standard daily dose, or pegylated, is caused by a combination of bone marrow inhibition and probably some other rapid acting mechanisms. Hematopoietic growth factors are increased as a consequence but cannot overcome the bone marrow suppression.