Abstract
Background/Aim
Venous thromboembolism (VTE), commonly manifesting as deep vein thrombosis (DVT) or pulmonary embolism (PE), ranks as the third most prevalent cardiovascular condition. Red cell distribution width (RDW) and red cell index (RCI)—both derived from complete blood count (CBC) parameters—have been linked to prognosis and mortality in PE. This study aimed to assess the predictive and prognostic value of RDW and RCI in PE patients, and to compare these markers between those with breast or lung cancer and those without malignancy.
Material and methods
A total of 133 patients diagnosed with PE between 2020 and 2023 were retrospectively analyzed. Among them, 81 had no malignancy, 33 had concurrent lung cancer, and 19 had breast cancer. RDW and RCI values were obtained from initial complete blood counts. RCI was calculated using hemoglobin, red blood cell, lymphocyte, and platelet counts. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis.
Results
RDW values were significantly higher in patients with lung or breast cancer compared to those without malignancy (p < 0.001 for both). No statistically significant differences were found in RCI values among the groups (p = 0.073). Additionally, no significant differences in RDW or RCI were observed according to mortality status within any group.
Conclusion
RDW was found to be significantly elevated in malignancy-associated PE and may serve as a useful predictive marker. However, the prognostic utility of RDW and RCI in relation to mortality was limited in all groups.
Introduction
One common and occasionally lethal type of venous thromboembolism(VTE) is acute pulmonary embolism (PE). Thromboembolic events predominantly arise in the context of a clinically apparent malignancy. Nonetheless, certain patients diagnosed with VTE may only be identified as having a malignancy at the time of the VTE occurrence or several months thereafter.1–3 Clinically evident VTE manifests in up to 10% of cancer patients.4–8 The type, location, stage of the tumor, and duration since diagnosis affect the risk of VTE, in addition to patient comorbidities and specific cancer treatments.9–16 Furthermore, research indicates that the diagnosis of VTE in cancer patients is linked to a higher mortality rate. Studies have shown that individuals with cancer-related pulmonary embolism have markedly elevated short- and long-term mortality, with one-year survival around 60 % and five-year survival only about 39 %. 17
Red blood cell distribution width (RDW) quantitatively assesses anisocytosis, or the variability in the size of circulating red blood cells.18,19 An elevated RDW signifies heightened red blood cell turnover and production. High RDW levels are frequently linked to anemia, hematologic disorders, oxidative stress, and overall impairment of erythropoiesis. 20 RDW has been significantly linked to unfavorable prognoses in individuals with cardiovascular conditions, particularly chronic heart disease cardiac failure (CHF) in intensive care units, accompanied by acute sepsis/septic shock, and more recently, with VTE and PE.21,22 Studies also have shown that elevated RDW correlates with heightened 30-day mortality as an independent risk factor in patients with acute PE.23,24
The red cell index (RCI), a composite parameter derived from hemoglobin, red blood cell, lymphocyte, and platelet counts, has recently been proposed as a novel biomarker reflecting both oxygen-carrying capacity and inflammatory status. To date, outside of Babaoglu & Ulaşlı's 2023 analysis, no other studies have directly investigated the role of RCI in PE. 25 A recent study identified RCI as an effective biomarker for predicting 3-month mortality in patients with acute ischemic stroke treated with intravenous thrombolysis. Notably, a positive correlation between RCI levels and mortality risk persisted even after adjusting for potential confounding variables 26
Although elevated RDW and RCI levels have been associated with poor outcomes in PE and thrombosis, limited data exist on this diagnostic and prognostic significance in patients with concomitant malignancy, particularly solid tumors such as breast and lung cancer—two of the most common cancer types known to increase thrombotic risk.
Therefore, this study was conducted to investigate the predictive and prognostic value of RDW and RCI in patients with PE, and to compare these markers between individuals with breast or lung cancer and those without malignancy.
Material and Methods
This retrospective, single-center study was conducted among patients aged 18 years or older who were diagnosed with PE between 2020 and 2023. Patients without malignancy who were diagnosed with PE, as well as those with a concurrent diagnosis of breast or lung cancer at the time of PE diagnosis within the past three years, were included in the study.
Patient Selection
Before initiating the present study, we conducted a pilot analysis at our institution to assess the distribution of pulmonary embolism across different malignancies. This preliminary analysis revealed that pulmonary embolism was most frequently observed in patients with lung and breast cancer, whereas the number of embolic events in other cancer types was insufficient for meaningful statistical evaluation. Based on these findings, only patients with lung and breast cancer were included in the present study to ensure adequate statistical power and reliable subgroup analysis.
Demographic data (age, sex, smoking status), PE diagnostic modality [computed tomography pulmonary angiography (CTPA), ventilation/perfusion (V/Q) scintigraphy, or clinical diagnosis], presence of deep vein thrombosis (DVT) at diagnosis, cancer type (breast or lung), metastatic status, and receipt of active oncologic treatment (chemotherapy or radiotherapy) were recorded. Complete blood count (CBC) parameters obtained at diagnosis were used to assess RDW and RCI. A follow-up period of one year was used to assess all-cause mortality after the diagnosis of pulmonary embolism. The follow-up duration and mortality variable were clearly defined and systematically recorded for each patient. Mortality was evaluated as all-cause mortality during the 1-year follow-up period. No deaths were directly attributable to pulmonary embolism; therefore, the mortality variable reflects overall mortality rather than embolism-related mortality. Patients with incomplete clinical or laboratory data were excluded from the final analysis to minimize potential bias due to missing data.
The exclusion criteria for the study were defined to eliminate potential confounding factors that could affect hematological parameters or thrombotic risk. Patients were excluded if they had a diagnosis of atrial fibrillation, rheumatoid arthritis, chronic kidney disease (stage ≥3), chronic liver failure, or known inherited thrombophilic disorders (eg, Factor V Leiden mutation, protein C/S deficiency, antithrombin III deficiency). Additionally, individuals younger than 18 years of age were excluded from the analysis.
RCI is determined by analyzing hemoglobin levels alongside red blood cell, lymphocyte, and platelet counts derived from full blood count assessments. RCI = [Red blood cell count x Hemoglobin (gr/L)]/(Lymphocyte count×Platelet count). 25 The RDW and RDW-sd value was recorded from the routine complete blood count at the time of embolism diagnosis. The normal reference range for RDW is from 11% to 16% and RDW-sd is from 35–56 fl in the hospital laboratory.
The Ethics Committee (No: 2023-12/122) approved the study. This research was conducted in conjunction with the Helsinki Declaration (revised in 2013).
Data analysis was performed using IBM SPSS 15.0 (SPSS Inc., Chicago, IL, USA) package program. Descriptive statistics were shown as mean ± standard deviation for variables with normal distribution, median (min—max) for variables with abnormal distribution, and nominal variables as number of cases and (%). When the number of groups was two, the significance of the difference in terms of means between groups was investigated using the t test, and the significance of the difference in terms of median values was investigated using the Mann Whitney test. When the number of groups was more than two, the significance of the difference in terms of means between groups was investigated using the ANOVA analysis of variance test, and the significance of the difference in terms of median values was investigated using the Kruskal Wallis test. Nominal variables were evaluated using Pearson Chi-Square or Fisher's Exact test. When investigating the relationship between continuous variables, the Spearman correlation test was used when the distribution was not normal, and the Pearson correlation test was used when it was normal. The results were considered statistically significant for p < 0.05. Variables with a p-value ≤ 0.10 in univariate analysis were considered for inclusion in multivariate models; however, none met this threshold, and therefore multivariate analysis was not performed.
Results
In our study, 45.9% of the 133 participants were male and 54.1% were female. The mean age was 61.55 ± 14.35 years, ranging from 18 to 90. Of the total participants, 60.9% had no cancer diagnosis, while 24.8% had lung cancer and 14.3% had breast cancer. The proportion of males was significantly higher in the lung cancer group compared to females (72.7% vs 27.3%, p = 0.009). The rate of current smoking was highest in the lung cancer group (51.5%), whereas 94.7% of the breast cancer group were non-smokers. In addition, the proportion of former smokers was notably higher in the lung cancer group (30.3%) (p < 0.001).
At the time of diagnosis, the rate of unknown DVT status was 69.7% in the lung cancer group, while the rate of DVT negativity was 36.8% in the breast cancer group (p = 0.041). Metastatic disease was present in 69.7% of patients with lung cancer and 73.7% of those with breast cancer (p = 0.760). The proportion of patients receiving active oncologic treatment (chemotherapy or radiotherapy) at the time of pulmonary embolism diagnosis was significantly higher in the breast cancer group (94.7%) compared to the lung cancer group (48.5%) (p = 0.001). Among those receiving treatment, 50.0% of lung cancer patients and 77.8% of breast cancer patients were receiving chemotherapy, while concurrent chemoradiotherapy was administered to 37.5% and 22.2% of patients, respectively (p = 0.140). The comparison of sex, smoking status, presence of DVT at diagnosis, metastatic status and oncologic treatment characteristics by cancer group is summarized in Table 1.
Comparison of Clinical and Demographic Features by Cancer status (N = 133).
KW: Kruskal-Wallis test, χ²: Chi-square test, PE: pulmonary embolism, CT: computed tomography, V/Q: ventilation-perfusion (V/Q) scintigraphy, DVT: deep vein thrombosis, RT: radiotherapy. Bold values indicate statistically significant p values (p < 0.05).
The median RDW value was 14.20 (13.50-14.90) in patients without malignancy, whereas it was 16.10 (14.50-17.70) in the lung cancer group and 16.60 (14.50-17.80) in the breast cancer group (p < 0.001). Pairwise comparisons revealed that both cancer groups had significantly elevated RDW levels compared to the non-cancer group (p < 0.001 for both). However, no significant difference in RDW values was observed between the lung and breast cancer groups (p = 1.000).
To further evaluate the diagnostic utility of RDW, Receiver Operating Characteristic (ROC) curve analysis was performed. The area under the curve (AUC) for RDW in predicting cancer-associated pulmonary embolism was 0.778 (95% CI: 0.698-0.846), with the highest accuracy achieved at a cut-off value of 15.3, yielding a sensitivity of 67.31% and a specificity of 86.42%. Additionally, the AUC values of RDW were 0.747 (95% CI: 0.654-0.824) for lung cancer and 0.883 (95% CI: 0.745-0.900) for breast cancer, with corresponding optimal cut-off values of 15.3 and 15.9, respectively. These findings indicate that RDW demonstrated good discriminatory ability for predicting cancer-associated pulmonary embolism, particularly in breast cancer cases. The AUC and optimal threshold statistics for RDW are illustrated in Figure 1.

Receiver Operating Characteristic (ROC) Curves Illustrating the Diagnostic Performance of Red Cell Distribution Width (RDW) in Predicting Cancer-Associated Pulmonary Embolism. (A) ROC Curve of RDW in the Overall Study Population. (B) ROC Curve of RDW in Patients with Lung Cancer (AUC = 0.747, 95% CI: 0.654-0.824; Optimal cut-off: 15.3). (C) ROC Curve of RDW in Patients with Breast Cancer (AUC = 0.883, 95% CI: 0.745-0.900; Optimal Cut-off: 15.9). RDW Showed the Highest Discriminative Ability for Pulmonary Embolism in Breast Cancer Cases.
The relationship between RDW levels and the presence of metastasis was analyzed. The median RDW value was 16.60 (IQR: 15.00-18.20) in patients with metastasis, and 15.60 (IQR: 14.50-17.40) in those without metastasis. There was no statistically significant difference in RDW levels between patients with and without metastasis (p = 0.374).
The median RCI value was 0.03 (IQR: 0.02-0.04) in individuals without cancer, 0.02 (IQR: 0.01-0.03) in the lung cancer group, and 0.03 (IQR: 0.02-0.04) in the breast cancer group. Although the median RCI appeared lower in the lung cancer group, no statistically significant difference was observed between the non-cancer and lung cancer groups (Kruskal–Wallis test = 5.234; p = 0.073). The distribution of RDW and RCI values according to cancer status is presented in Table 2.
RDW and RCI Distributions According to Cancer Status.
KW: Kruskal-Wallis test; RDW: Red Cell Distribution Width; RCI: Red Cell Index.
In the subgroup of patients with metastasis, the median RCI value was 0.02 (IQR: 0.01-0.03) in the lung cancer group and 0.03 (IQR: 0.02-0.04) in the breast cancer group. Within the lung cancer group, RCI levels were significantly lower in patients with metastasis compared to those without metastasis (Z = 2.161; p = 0.031). The distribution of RCI values according to metastatic status in lung and breast cancer patients is presented in Table 3.
RCI Values According to Metastasis status in Lung and Breast Cancer.
RCI: Red Cell Index; IQR: Interquartile Range; Z: Mann-Whitney U test z-value.
Overall mortality rates were evaluated across study groups. As noted in the Methods section, mortality was defined as all-cause mortality, since no deaths were directly attributed to pulmonary embolism. No mortality was observed in the non-cancer group, with 100% of individuals surviving during the follow-up period. In the lung cancer group, the mortality rate was calculated as 33.3% (n = 11), while the survival rate was 66.7% (n = 22). In the breast cancer group, the mortality rate was 10.5% (n = 2), and the survival rate was 89.5% (n = 17).
RDW and RCI values were analyzed according to mortality status within each diagnostic group. In the non-cancer group, RDW and RCI values could not be evaluated for deceased individuals, as no mortality was observed. Among survivors in this group, the median RDW was 14.20 (IQR: 13.50-14.90) and the median RCI was 0.03 (IQR: 0.02-0.04). In the lung cancer group, when RDW values were compared by mortality status, the median RDW was 17.00 (IQR: 14.10-17.40) in deceased patients and 15.80 (IQR: 14.50-18.20) in survivors; however, the difference was not statistically significant (Z = -0.115; p = 0.909). Similarly, the median RCI was 0.02 (IQR: 0.01-0.02) in patients who died and 0.02 (IQR: 0.01-0.04) in survivors, with no statistically significant difference (Z = -0.573; p = 0.567). In the breast cancer group, the median RDW was 15.60 (IQR: 14.50-16.70) in deceased patients and 16.60 (IQR: 15.00-17.80) in those who survived; the difference was not statistically significant (Z = -0.466; p = 0.642). The median RCI was 0.02 (IQR: 0.01-0.02) in deceased patients and 0.03 (IQR: 0.02-0.04) in survivors, which also did not reach statistical significance (Z = -1.196; p = 0.232). The distribution of mortality outcomes by group and RDW- RCI values according to mortality status is shown in Table 4.
RDW and RCI Values According to Mortality in Cancer and non-Cancer Groups.
Z: Mann-Whitney U test; RDW: Red Cell Distribution Width; RCI: Red Cell Index.
Discussion
In this study, we comprehensively evaluated both the predictive and prognostic value of RDW and RCI in patients diagnosed with pulmonary embolism in the context of underlying malignancy, specifically lung and breast cancer. Our findings demonstrated that RDW values were significantly elevated in patients with cancer-associated embolism compared to those without malignancy, which may reflect the enhanced inflammatory and prothrombotic state commonly observed in malignancy-related thromboembolic events. No significant association was found between RCI and embolism, nor were RDW or RCI values significantly related to short-term mortality in cancer patients. These results suggest limited prognostic utility of both markers despite RDW's potential diagnostic role.
Previous studies have reported that RDW may serve as a useful biomarker in the diagnosis of PE. A meta-analysis by Dai et al (2023) also indicated that patients with VTE, including PE, had consistently higher RDW levels compared to non-thrombotic populations, supporting its diagnostic relevance. 27 The prognostic value of RDW in PE has been highlighted in several studies. Zhou et al (2017) reported that elevated RDW levels were independently associated with 30-day mortality in acute PE patients. 24 Similarly, Xing et al (2020), in a meta-analysis including over 4000 patients, found that each 1% increase in RDW was associated with a 19% increase in mortality risk in PE patients. 28 These findings have positioned RDW as a readily available and cost-effective biomarker for short-term mortality prediction in PE. In contrast to the established association between elevated RDW and mortality in general PE populations, our findings indicate that although RDW levels were generally elevated in cancer patients with embolism, this elevation did not correlate with short-term mortality. The limited prognostic value of RDW observed in our study may be attributed to the multifactorial influences present in cancer patients, including chronic inflammation, tumor burden, anemia, and treatment-related hematologic alterations. In this context, RDW likely reflects a broad spectrum of cancer-associated physiological changes rather than embolism-specific risk, thereby reducing its prognostic specificity. While RDW may retain diagnostic significance in detecting embolism among patients with malignancy, its predictive capacity for mortality appears to be confounded by the underlying cancer-associated inflammatory state. These findings underscore the importance of developing integrated risk assessment models tailored to cancer populations, incorporating malignancy-specific variables to improve prognostic accuracy in thromboembolic events. The association between increased RDW and thromboembolic risk in malignancy may be explained by systemic inflammation, oxidative stress, and impaired erythropoiesis induced by tumor burden and chemotherapy. These mechanisms are known to contribute to red cell anisocytosis and endothelial dysfunction, promoting a prothrombotic state. This pathophysiological interplay may account for the observed elevation of RDW in patients with cancer-associated pulmonary embolism, supporting its potential role as a hematologic indicator of inflammatory and thrombotic activity.
In addition to RDW we also examined the potential diagnostic and prognostic relevance of the RCI, a lesser-studied erythrocyte-based parameter in the context of PE. While RDW has been widely investigated, studies evaluating RCI remain limited. One of the few studies on the subject, conducted by Babaoglu and Ulasli (2023), found that RCI was not significantly associated with either PE diagnosis or 30-day mortality, although it may reflect subclinical inflammatory or hematologic alterations that do not translate into clinical outcomes. 25 Our findings partially support this view. In our cohort, although the median RCI appeared lower in the lung cancer group, no statistically significant difference was observed between the non-cancer and lung cancer groups. However, among lung cancer patients with metastasis, the RCI was significantly lower compared to those without metastasis. This may suggest that advanced disease alters erythropoiesis or red cell morphology, contributing to decreased RCI. The overall lack of significant association between RCI and embolism or mortality outcomes may be attributed to the multifactorial and nonspecific nature of the index, its sensitivity to a broad range of hematologic influences, and the absence of validated thresholds for clinical interpretation. Therefore, while RCI may reflect certain biological changes in advanced cancer, its independent diagnostic or prognostic value in cancer-associated PE appears to be limited.
This study has several limitations that should be acknowledged. First, the retrospective design inherently introduces the risk of selection bias and limits the ability to establish causal relationships. Second, the sample size, particularly within subgroups such as metastatic lung and breast cancer patients, was relatively small, potentially reducing the statistical power to detect subtle associations, especially in mortality analyses. Third, the heterogeneity of cancer treatments (eg, type, timing, and duration of chemotherapy or radiotherapy) and disease stages were not fully controlled for, which may have influenced hematologic parameters such as RDW and RCI. Lastly, the single-center nature of the study may limit the generalizability of the findings to broader and more diverse populations. To our knowledge, no prior study has concurrently investigated RDW and RCI in relation to both thromboembolic risk and mortality in patients with cancer-associated pulmonary embolism, underscoring the potential contribution of our findings to the current body of literature. These results reflect the complex and multifactorial nature of thromboembolic events in oncology and underscore the need for more accurate and sensitive biomarkers to enhance risk stratification and support clinical decision-making. Further validation through prospective, multicenter studies with larger cohorts and standardized methodologies is essential to determine the clinical utility and optimal thresholds of these indices. Moreover, our findings highlight the importance of interpreting hematologic markers within the comprehensive clinical framework of malignancy when evaluating thromboembolic risk and prognosis.
Conclusion
Our findings suggest that RDW is a useful and accessible biomarker for identifying embolism in patients with underlying malignancy, particularly in breast and lung cancer. Until further validation, RDW may be cautiously incorporated into diagnostic workflows as a supplementary marker in cancer-associated PE.
Footnotes
Acknowledgements
The authors thank all the patients who participated in this study.
Ethical statement
The writers are responsible for all aspects of the writing, including ensuring that any concerns about the work's quality or credibility are thoroughly investigated and resolved. University of Health Sciences, Ankara Oncology Training and Research Hospital Ethics Committee approved this study (No:2024-05/66). This research was carried out in conjunction with the Helsinki Declaration (as revised in 2013).
Patient Consent for Publication
Not applicable.
Author Contributions
D.Y, E.S.A. and O.D.B. conceptualized the present study and wrote the manuscript; D.K, T.D and O.D.B. collected, analyzed, and interpreted the data. O.D.B., E.S.A. and M.SD were responsible for drafting the manuscript; the manuscript was reviewed by all authors. All authors have read and agreed to the published version of the manuscript.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The present study was supported by the University of Health Sciences, Ankara Oncology Training and Research Hospital Ethics Committee (No: 2023-12/122).
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Availability of Data and Materials
The datasets generated and/or analyzed during the current study are not publicly available due to institutional and ethical restrictions but are available from the corresponding author upon reasonable request.
