Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality Julia Riedl 1 , Florian Posch 1 , Oliver Ko ¨ nigsbru ¨ gge 1 , Felix Lo ¨ tsch 1 , Eva-Maria Reitter 1 , Ernst Eigenbauer 2 , Christine Marosi 3 , Ilse Schwarzinger 4 , Christoph Zielinski 3 , Ingrid Pabinger 1 , Cihan Ay 1 * 1 Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria, 2 Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria, 3 Clinical Division of Oncology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria, 4 Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Abstract Background: Cancer patients are at high risk of developing venous thromboembolism (VTE). Red cell distribution width (RDW) has been reported to be associated with arterial and venous thrombosis and mortality in several diseases. Here, we analyzed the association between RDW and other red blood cell (RBC) parameters with risk of VTE and mortality in patients with cancer. Methods: RBC parameters were measured in 1840 patients with cancers of the brain, breast, lung, stomach, colon, pancreas, prostate, kidney; lymphoma, multiple myeloma and other tumor sites, that were included in the Vienna Cancer and Thrombosis Study (CATS), which is an ongoing prospective, observational cohort study of patients with newly diagnosed or progressive cancer after remission. Primary study outcome is occurrence of symptomatic VTE and secondary outcome is death during a maximum follow-up of 2 years. Results: During a median follow-up of 706 days, 131 (7.1%) patients developed VTE and 702 (38.2%) died. High RDW (. 16%) was not associated with a higher risk of VTE in the total study cohort; in competing risk analysis accounting for death as competing variable the univariable subhazard ratio (SHR) was 1.34 (95% confidence interval [CI]: 0.80–2.23, p = 0.269). There was also no significant association between other RBC parameters and risk of VTE. High RDW was associated with an increased risk of mortality in the total study population (hazard ratio [HR, 95% CI]: 1.72 [1.39–2.12], p,0.001), and this association prevailed after adjustment for age, sex, hemoglobin, leukocyte and platelet count (HR [95% CI]: 1.34 [1.06–1.70], p = 0.016). Conclusions: RDW and other RBC parameters were not independently associated with risk of VTE in patients with cancer and might therefore not be of added value for estimating risk of VTE in patients with cancer. We could confirm that high RDW is an independent predictor of poor overall survival in cancer. Citation: Riedl J, Posch F, Ko ¨ nigsbru ¨gge O, Lo ¨ tsch F, Reitter E-M, et al. (2014) Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality. PLoS ONE 9(10): e111440. doi:10.1371/journal.pone.0111440 Editor: Hugo ten Cate, Maastricht University Medical Center, Netherlands Received July 9, 2014; Accepted September 28, 2014; Published October 27, 2014 Copyright: ß 2014 Riedl et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This study was supported by funds of the ‘‘Oesterreichische Nationalbank’’ (Anniversary Fund, project number 14744) and by a grant from the ‘‘Hochschuljubila ¨umsstiftung der Stadt Wien’’ (http://www.oenb.at/en/About-Us/Research-Promotion/The-OeNB-Anniversary-Fund.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The Vienna Cancer and Thrombosis Study (CATS) was supported by funds from the ‘‘Oesterreichische Nationalbank’’ (Anniversary Fund, project number 14744) and by a grant from the ‘‘Hochschuljubila ¨ umsstiftung der Stadt Wien’’. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. * Email: cihan.ay@meduniwien.ac.at Introduction Red cell distribution width (RDW) is a parameter of the complete blood count (CBC) that describes the size variation of red blood cells (RBC). It is routinely measured by most of the modern hemocytometers and is calculated by dividing the standard deviation of the mean corpuscular volume (MCV) by the respective actual MCV, and is expressed as percentage. A high RDW represents a large variation of the RBC volume, called anisocytosis, and is found in conditions with an increased number of small or large RBC. Hence, RDW can be used to discriminate between different forms of anemia, since iron deficiency anemia or megaloblastic anemia are accompanied with elevated RDW, whereas in thalassemia RDW is usually normal [1–3]. Other parameters routinely given by CBC that provide information about RBC are hematocrit, hemoglobin concentration, MCV, mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). PLOS ONE | www.plosone.org 1 October 2014 | Volume 9 | Issue 10 | e111440