Increased plasma viscosity as a reason for inappropriate erythropoietin formation.

Abstract

The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenstrom's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to -40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels.Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients. (J. Clin. Invest. 1993. 91:251-256.)

Erythropoietin

“…Such a pathogenetic process is likely the basis for the marked anemia often encountered in cancer patients who have been treated with cis-platinum or individuals suffering from chronic cadmium intoxication (Horiguchi et al 2000). Epo production is also inhibited in patients with increased plasma viscosity owing to monoclonal dysproteinemias (Singh et al 1993). …”

The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal

“…Unfortunately, because erythropoietin is metabolized by its target cells 87 and erythropoietin production is suppressed by erythrocytosis 88 or an increase in blood viscosity, 89 an increase in the red cell mass is associated with down-regulation of erythropoietin production unless hypoxia is severe. 88 Thus, many patients with hypoxic erythrocytosis have a normal serum erythropoietin level.…”

Polycythemia vera: myths, mechanisms, and management

“…It should not be surprising, therefore, that therapy with recombinant erythropoietin, 117 androgenic steroids, 118 and even blood transfusion 119 also leads to a reduction in plasma volume; the mechanisms involved are unknown but may in part be protective since increasing whole blood viscosity suppresses endogenous erythropoietin production. 76,120 By contrast, in polycythemia vera where erythropoiesis is autonomous and erythropoietin production is suppressed, as the red cell mass increases the plasma volume may be unchanged or increase 121 until the hematocrit level is more than 60%. 122 Unfortunately, the hematocrit level, whether directly determined by centrifugation or calculated from the mean corpuscular volume (MCV) and the red cell count, will not reflect these changes because even under normal circumstances, the distribution of red cells and plasma is not uniform throughout the circulatory system.…”