Red Cell Distribution Width (RDW) is a quantitative measure of the variability in red blood cell (RBC) size (anisocytosis), expressed as a percentage[1]. It is routinely reported as part of the complete blood count (CBC) and historically used primarily in the differential diagnosis of anemia. Elevated RDW is seen in iron deficiency anemia, megaloblastic anemia, and hemoglobinopathies due to increased heterogeneity in RBC size[2].

In recent decades, observational studies have expanded the clinical relevance of RDW beyond hematology, demonstrating associations with cardiovascular disease, infection, malignancy, and systemic inflammatory states. Increased RDW has been postulated to reflect underlying inflammation, oxidative stress, and poor nutritional status factors common to many chronic and acute conditions. Moreover, RDW has been correlated with disease severity and outcomes, including mortality, length of hospital stay, and response to therapy[3].

Despite accumulating evidence, the routine integration of RDW into clinical prognostic models remains limited. This study aims to evaluate the diagnostic and prognostic value of RDW in a cohort of hospitalized patients with diverse clinical conditions, focusing on both hematologic and non-hematologic disorders [4-5].

This prospective observational study was conducted over 12 months at the Department of Internal Medicine and Department of Hematology in a tertiary care hospital.

Participants

A total of 100 adult patients (≥18 years) admitted with clinical indications requiring CBC were enrolled. Patients with recent transfusions (within 3 months) or known hemoglobinopathies were excluded.

Data Collection

Demographic data, clinical diagnosis, comorbidities, vital signs, and laboratory results were recorded at admission. RDW values were obtained via automated hematology analyzers as part of routine CBC. Additional investigations included hemoglobin (Hb), mean corpuscular volume (MCV), total leukocyte count (TLC), platelets, C-reactive protein (CRP), liver function tests (LFTs), renal function tests (RFTs), and echocardiography where applicable.

Definitions

• Normal RDW: 11.5–14.5% (laboratory reference range).
• Elevated RDW: >14.5%.
• Hematologic Disorders: Classified into anemic conditions, leukemias, and other bone marrow pathology.
• Non-Hematologic Disorders: Included cardiovascular disease (e.g., heart failure), chronic liver disease, chronic kidney disease, and systemic inflammatory conditions (e.g., sepsis).

Outcomes

• Primary outcomes: Association of RDW with specific diagnoses and disease severity.
• Secondary outcomes: Length of hospital stay and in-hospital mortality.

Statistical Analysis

Data were analyzed using SPSS version 25. Continuous variables are presented as mean ± SD or median (IQR) and categorical variables as frequencies and percentages. Comparisons used t-tests or χ² tests as appropriate. A p-value <0.05 was considered significant.

Among 100 patients, the mean age was 52.6 ± 16.4 years (range 18–85), with 58 males and 42 females. The primary diagnoses are summarized in Table 1.

Table 1. Distribution of Diagnoses (n=100)

The mean RDW values in different diagnostic groups are shown in Table 2.

Table 2. RDW Values by Diagnosis Category

Correlation with Laboratory and Clinical Parameters

RDW showed significant positive correlations with CRP levels (r = 0.45, p <0.01) and length of hospital stay (r = 0.31, p = 0.02). In contrast, RDW inversely correlated with hemoglobin (r = -0.51, p <0.001). Table 3 illustrates selected correlations.

Table 3. Correlations of RDW with Clinical/Laboratory Parameters

Among 100 patients, there were 12 in-hospital deaths. The mean RDW in non-survivors was significantly higher (18.9 ± 2.8) compared to survivors (15.9 ± 2.0, p <0.001). Additionally, patients with elevated RDW had longer median hospital stays. Table 4 summarizes outcomes based on RDW status.

Table 4. RDW Status and Outcomes

RDW in Hematologic Disorders

In our cohort, RDW was elevated across all hematologic malignancies and anemias. Particularly, iron deficiency and megaloblastic anemia showed RDW >18%, consistent with increased anisocytosis due to varied RBC size from ineffective erythropoiesis and nutrient deficiencies. These findings align with earlier studies demonstrating RDW as a sensitive marker for differentiating anemia types[6].

Although RDW alone cannot replace specific tests (e.g., ferritin, B12 levels), when combined with standard indices such as MCV, it enhances diagnostic precision. Our study observed that all patients with anemia types had elevated RDW, suggesting high sensitivity[7].

RDW in Non-Hematologic Disorders

In non-hematologic disease categories, RDW was significantly elevated in patients with chronic inflammatory states, heart failure, and liver/kidney dysfunction. The observed positive correlation between RDW and CRP (an inflammatory marker) supports the link between systemic inflammation and erythrocyte size variability. In heart failure, elevated RDW has been linked in other studies to adverse outcomes, possibly reflecting neurohumoral activation, nutritional deficiencies (iron, folate), and inflammation[8-9].

Chronic liver disease patients often display elevated RDW due to altered erythropoiesis, hypersplenism, and nutritional derangements. Similarly, chronic kidney disease is characterized by anemia of chronic disease with ineffective erythropoiesis, resulting in elevated RDW[10].

Prognostic Implications

The association between elevated RDW and longer hospital stays underscores its potential as a marker of disease severity. Notably, elevated RDW correlated with in-hospital mortality, a finding previously reported in acute myocardial infarction, sepsis, and heart failure literature. These results position RDW as a useful prognostic marker, especially since it is inexpensive and already part of routine testing[11-12].

Mechanisms Linking RDW to Disease Outcomes

The exact mechanisms linking elevated RDW with poor outcomes remain under investigation. Proposed mechanisms include:

• Inflammation: Cytokine-mediated impairment of erythropoiesis increases anisocytosis.
• Oxidative stress: Damages RBC membranes, shortening lifespan and increasing size variability.
• Nutrient deficiencies: Iron, B12, folate deficits disturb normal erythropoiesis.

Bone marrow dysfunction: From chronic disease, malignancy, or aging

This study is limited by its single-center design and modest sample size. Being cross-sectional, causal relationships cannot be established. RDW cut-offs were based on laboratory reference ranges and may differ across populations. Longitudinal studies with larger cohorts are needed to validate prognostic thresholds.

RDW is a readily available marker with significant diagnostic and prognostic value in both hematologic and non-hematologic diseases. Elevated RDW correlates with disease severity, systemic inflammation, prolonged hospitalization, and mortality, underscoring its potential utility in routine clinical practice. Integration of RDW into diagnostic algorithms and risk stratification models may enhance patient care without additional cost.

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