Use of alveolar carbon monoxide to measure the effect of ribavirin on red blood cell survival†

Abstract

A major side effect of ribavirin (RBV) treatment is anemia. While this anemia is thought to result from increased RBC turnover, RBC survival has not been determined in subjects receiving RBV due to the complexity of the techniques commonly used to quantitate RBC life span. We recently described a simple, rapid, non-invasive technique that utilizes measurements of alveolar carbon monoxide (CO) concentration to determine RBC survival. In the present report, this method was employed to assess RBC survival in patients receiving RBV for hepatitis C. Each of the 31 measurements of RBC survival in 12 subjects with RBV-associated anemia was below the lower limit of normal (77 days), and the average survival (46 ± 14 days) in these subjects was only about 38% of that of healthy controls (122 ± 23 days). Five hepatitis C patients not undergoing RBV treatment had normal RBC survivals (112 ± 17 days). While the mean reticulocyte percentage was significantly elevated in subjects treated with RBV, 59% of these measurements fell within the limits of normal. We conclude that RBV-associated anemia consistently is associated with reduced RBC survival as determined from breath CO measurements and that this reduced survival frequently is not associated with an elevated reticulocyte count. Am.

Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy

“…Further, with the same parameter values, we estimate that the RBC lifespan is 38 days (95% CI: 19–55 days) in Japanese patients with <1000 µM and 33 days (95% CI: 14–53 days) in Japanese patients with >1000 µM. These estimates of the RBC lifespan are in close agreement with independent estimates, 39±13 days, from measurements of alveolar carbon monoxide [49], [50], presenting another successful test of our model. Finally, we find that our predictions of the dependence of on and using the same parameters above are also in agreement with observations in the Japanese patients [47] (Fig.…”

“…This dramatic accumulation of ribavirin may induce oxidative damage and result in enhanced extra vascular death of RBCs [12]. Indeed, RBC lifespan decreased from 107±22 d in HCV patients not exposed to ribavirin to 39±13 d in HCV patients undergoing treatment with ribavirin [49], [50]. The shortened RBC lifespan creates an imbalance between RBC production and death and results in a decline in the RBC population.…”

Shortened Red Blood Cell Lifespan Is Related to the Dose of Erythropoiesis‐Stimulating Agents Requirement in Patients on Hemodialysis

“…Virtue et al. (20) and Mitlyng et al. (21) also conducted studies of the RBC lifespan using respired CO levels, finding that reticulocyte counts did not rise proportionately to the decrease in RBC lifespan in patients with hepatitis C treated with ribavirin or chronic disease.…”

Combination effect of ribavirin and erythropoietin treatment on hemoglobin A1c in a diabetic patient with chronic hepatitis C

“…RBV has been shown to induce reversible hemolytic anemia with shortened erythrocyte survival. 5,6 This anemia would be more pronounced with a combination of IFN and RBV because the myelosuppressive effect of IFN inhibits the bone marrow to compensate for RBV-induced hemolysis. 7 In addition, erythropoietin (EPO), commonly used for anemia related to HCV therapy, can stimulate production of red blood cells with decreased mean erythrocyte age.…”