Erythrocytosis in Hepatocellular Carcinoma: A Compensatory Phenomenon

Abstract

Summary. Red cells were removed by phlebotomy in nine patients having erythrocytosis associated with hepatocellular carcinoma. This resulted in an increase in the plasma levels of erythropoietin in seven; the rise was statistically significant in three. It suggests that, in the absence of systemic hypoxia, erythrwytosis develops in hepatocellular carcinoma as a compensatory response to local hypoxia in the liver. However, no rise in the 24 hr urinary output of erythropoietin was observed in any of the patients. It is postulated that this may be due to the presence in urine of inhibitors to erythropoietin.

Epidemiology and Prognosis of Paraneoplastic Syndromes in Hepatocellular Carcinoma

“…Paraneoplastic hypercholesterolemia is believed to be due to dysregulation of LDL receptors leading to autonomous cholesterol production by neoplastic hepatocytes [21–24]. Paraneoplastic erythrocytosis is believed to occur as a result of increased tumor erythropoietin produced by the HCC or as a compensatory response to local hypoxia produced by tumor necrosis [25–27]. The etiology of paraneoplastic hypercalcemia in HCC has been attributed to the production of a variety of hormonal substances by the neoplastic hepatocytes including parathyroid hormone related peptides (PTH-RP) [28], nephrogenous cyclic AMP [29], prostaglandins [30], and tumor-related calmodulin [31].…”

Erythrocytosis caused by an erythropoietin-producing hepatocellular carcinoma

“…The mechanism of production of Epo by tumor cells is still uncertain in spite of having been investigated [11][12][13][14][15][16]. It has been suggested that local hypoxia generated in large HCC might stimulate the production of Epo [17]. It has been shown in vitro in hepatoma cell lines that Epo expression increases greatly in response to hypoxia [18][19][20].…”

Secondary Polycythemia in Hepatocellular Carcinoma: Treat or No Treat

“…It may becasue repeated phlebotomies could cause iron deficiency with microcytic erythrocytes that can actually increase rather than decrease blood viscosity and somehow induce erythrocytosis due to compensatory effect. 19 In healthy men, a single 500-mL whole-blood donation results in a substantial loss of heme iron (i.e., 200-250 mg) and decreases serum ferritin levels by 44%. Thus, phlebotomy without a proper monitoring of blood viscosity can potentially accentuate rather than decrease the risk of a cardiovascular or cerebrovascular accident.…”