HDCN Article Review/Hyperlink

Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA

The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin

N Engl J Med (Aug) 339:584-590 1998

The abstract of this article is available from the NEJM: Click here.

For the abstract to a related abstract in the same issue by Kaufman et al (IV vs. subQ EPO VA Study), also available from the NEJM: Click here.

For an accompanying editorial: Click here.

The study by Besarab et al of the effects of different target hematocrits in epoetin-treated hemodialysis patients with cardiac disease emphasizes the difference in information yielded from cross-sectional studies as compared with prospective interv entional studies. Previous cross-sectional studies have demonstrated an inverse relation between hematocrit and mortality risk in dialysis patients (Madore et al. J Am Soc Nephrol 1997; 8:1921. In accordance with these studies, Besarab et al found that, w ithin both groups, patients with lower hematocrits had the highest mortality rate. However, there was no benefit of increasing the target hematocrit, the mortality tended to be higher in the normal-hematocrit group than in the low-hematocrit group. This p aradox could possibly be explained by the fact that factors known to cause resistance to epoetin, i.e., inflammation, hypoalbuminemia, malnutrition and low dose of dialysis also are associated with a higher risk of death. In addition, impaired response to epoetin and more severe anemia in these patients may have prompted the investigators to administer more intravenous iron, which was associated with a higher mortality risk. The difficulties of adjusting for these confounding variables may have been under estimated in previous cross-sectional studies and it would be clarifying if the authors could provide an analysis of the influence of such factors on mortality risk in the present study.

Indeed, the negative effects exerted of normal as compared with low hematocrit values raises a number of issues regarding the potential mechanisms involved. In experimental studies, epoetin have been shown to induce angiogenesis and an increase in blood pressure. Whether high intravenous doses of epoetin have such negative effects in humans remain speculative. The fear that a higher blood viscosity may increase the risk for systemic thrombembolic and cardiac events was not corroborated in the present study. However, the 10 % higher incidence of thrombosis of the vascular access (39 % in the normal -hematocrit group) may be one negative factor associated with a subsequent higher mortality rate. Thrombosis of the vascular access may especially in patients with vascular disease be followed by a series of negative events such as hospitalisations, several minor surgical procedures, infections, poor dialysis and malnutrition which could increase morbidity and mortality rates.

Peter Bárány (Peter.Barany@klinvet.ki.se)
Stockholm, - Sunday, October 18, 1998 at 12:10:07 (PDT)

why and how are hematocrits higher in males?
brian (bgreen0401@aol.com)
plano, tx - Sunday, September 22, 2002 at 21:23:09 (PDT)