title: Thrombocytosis and venous thromboembolism in cancer patients with chemotherapy induced anemia may be related to ESA induced iron restricted erythropoiesis and reversed by administration of IV iron.
abstract: ESA therapy can increase hemoglobin, decrease blood transfusions, and improve quality of life in patients with chemotherapy induced anemia (CIA). Despite its benefits, ESA therapy increases the risk of venous thromboembolism (VTE) in cancer patients by 50% and can also cause iron restricted erythropoiesis in CIA patients, which may augment the tendency to develop VTE. We postulated that thrombocytosis, a risk factor for VTE in cancer patients, in CIA patients on ESA therapy might be a result of ESA induced iron restricted erythropoiesis. We performed a retrospective analysis of 187 CIA patients who were randomized to receive weekly Epoetin and IV ferric gluconate, oral ferrous sulfate, or no iron for 8 weeks. Nineteen patients experienced 29 VTEs, and patients, whose platelets increased to ≥350,000 cells/uL were three times more likely to experience a VTE (OR 2.9, P = 0.036, logistic regression) with a four times greater incidence of VTE (IRR 4.4, P = 0.001, Poisson regression). Patients treated with IV iron were significantly less likely to develop platelets of ≥350,000 cells/uL (IRR 0.7, P = 0.013, Poisson regression) and had a decreased incidence of VTE. Our study suggests that ESA associated VTE in CIA patients may be, in part, related to the thrombocytosis of ESA induced iron restricted erythropoiesis and may be countered by IV iron.
authors.affiliation: Department of Medicine, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania 19106, USA. davidhenry@pennoncology.com
authors.forename: David H
authors.initials: DH
authors.lastname: Henry
authors.forename: Naomi V
authors.initials: NV
authors.lastname: Dahl
authors.forename: Michael A
authors.initials: MA
authors.lastname: Auerbach
mesh_terms: D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D018798:Anemia, Iron-Deficiency / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005290:Ferric Compounds / Q000627:therapeutic use; D005296:Ferrous Compounds / Q000627:therapeutic use; D006397:Hematinics / Q000009:adverse effects* / Q000627:therapeutic use; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009369:Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D013922:Thrombocytosis / Q000139:chemically induced*; D019851:Thrombophilia / Q000139:chemically induced / Q000209:etiology; D054556:Venous Thromboembolism / Q000139:chemically induced* / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D005290:Ferric Compounds; D005296:Ferrous Compounds; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; C020748:ferrous sulfate; D000068817:Epoetin Alfa; D007501:Iron; C035552:ferric gluconate