Red Blood Cell Distribution Width and Its Association with Other Hematological Parameters among Admitted Congestive Heart Failure Patients in Hiwot Fana Specialized University Hospital, Harar, Ethiopi
Published Date: Sep 15, 2017
Red Blood Cell Distribution Width and Its Association with Other Hematological Parameters among Admitted Congestive Heart Failure Patients in Hiwot Fana Specialized University Hospital, Harar, Ethiopia
Fekadu Urgessa 1* and Lemma Negassa2
1Medical Laboratory Science Department, College of Health Science, Addis Ababa University, Ethiopia
2School of Nursing and Midwifery, Health and Medical College, Haramaya University, Ethiopia
*Corresponding author: Fekadu Urgessa, Medical Laboratory Science Department, College of Health Science, Addis Ababa University, Ethiopia, E-mail: firstname.lastname@example.org.
Citation: Urgessa F, Negassa L (2017) Red Blood Cell Distribution Width and Its Association with Other Hematological Parameters among Admitted Congestive Heart Failure Patients in Hiwot Fana Specialized University Hospital, Harar, Ethiopia. J App Hem Bl Tran 1(1): 102
Background: Red blood cell distribution width (RDW) has emerged as a new prognostic biomarker in cardiovascular diseases. Its additional value in risk stratification of patients with congestive heart failure has not yet been established. The evidence associating red cell distribution width with a higher risk of mortality has been expanding since the initial report of its prognostic utility in heart failure patients.
Objectives: To determine the value of RDW and its association with other hematological parameters among admitted Congestive Heart Failure (CHF) patients in Hiwot Fana Specialized University Hospital, Harar, Ethiopia from September 2016 to March 2017
Methodology: Cross-sectional study design was conducted among admitted CHF patients in Hiwot Fana Specialized University Hospital. Sample was collected during admission and red blood cell distribution width and other hematology parameters were analyzed by Cell Dyn Ruby hematology analyzer, Abbott, USA. Collected data entered into Epi data and then exported to SPSS version 20 for analysis. Statistical significance was set at p < 0.05.
Results: The participants of this study were 164 (87 for confirmed CHF patients & 77 apparently healthy individual for control group). Mean age of the study participants for CHF patients 42.84 (standard deviation + 18.32 years) in years, 59.8% were female participants. More than 86% of the RDW determined among confirmed CHF patient was out of local normal reference range (11–14.4%). The RDW ranged from 12.60 to 36.30% (median 17.6%) and was correlated with Hemoglobin (Hgb) (Beta = -0.212 p = 0.044 95% CI -0.433 to -0.006), Mean Cell Hemoglobin Concentration (MCHC) (Beta -0.213, p = 0.044, 95% CI -26.62 to - 0.40) and Plateletcrit (PCT) (Beta -0.213, p = 0.044, 95% CI -26.62 to -0.40). Anemia was prevalent (70.2%) among CHF patients and the normocytic normochromic type of anemia was more prevalent than the other types of anemia.
Conclusion and Recommendation: Red cell Distribution Width was increased among CHF patients when compared to local reference value for RDW. The RDW determined had inverse correlation with other hematological parameters such Hgb, MCHC and PCT. Therefore, RDW could be used for diagnosis and prognosis purpose since it was specifically increased among CHF patients if confirmed by further studies. Other diseases such as anemia which was highly prevalence need attention among CHF patients.
Red blood cell; Prognostic biomarker; Hematological parameters
CVD: Cardiovascular Disease; CI: Confidence Interval; CHF: Congestive Heart Failure; EPO: Erythropoietin; Hgb: Hemoglobin; MCHC: Mean Cell Hemoglobin Concentration; MCV: Mean Corpuscular Volume; PCT: Plateletcrit; RBC: Red Blood Cell; RDW: Red blood cell distribution Width; SD: Standard Deviation; WHO: World Health Organization.
The epidemic of CVD in Sub-Saharan African (SSA) is driven by multiple factors working collectively. Lifestyle factors such as diet and smoking contribute to the increasing rates of CVD in SSA. Some lifestyle factors are considered gendered in that some are salient for women and others for men. For instance, obesity is a predominant risk factor for women compared to men, but smoking still remains mostly a risk factor for men .
Over the past decade, there has been a literal explosion of studies examining various prognostic biomarkers in patients with heart failure. Some of these biomarkers such as the natriuretic peptides directly reflect pathophysiologic processes in the diagnosis, while the prognostic links for other ‘‘heart failure biomarkers’’ remain less well-defined .
The RDW is a RBC measurement that quantitates red cell volume heterogeneity that is provided by the more modern automated hematology analyzers and reflects the range of RBC sizes measured within a sample. It has been proposed to be useful in early classification of anemias and for characterizing microcytic anemias, particularly distinguishing between iron deficiency anemia (high RDW, normal to low MCV) and uncomplicated heterozygous thalassemia (normal RDW, low MCV) .
Nowadays, the evidence associating RDW with a higher risk of mortality has been expanding since the initial report of its prognostic utility in heart failure patients. RDW has also been shown to independently predict overall and cardiovascular (CV) mortality in the general population and various high-risk populations .
Tonelli et al have found a graded independent relation between higher levels of RDW and the risk of heart failure, cardiovascular events, and all-cause death in people with prior myocardial infarction but no evidence of heart failure at baseline. They also recommend further explanation for the association between RDW and adverse clinical outcomes .
Red blood cell distribution width has emerged as a new prognostic biomarker in cardiovascular diseases. Its additional value in risk stratification of patients with chronic heart failure has not yet been established. It appears to be prognostically meaningful, but this is an empty finding if such risk cannot be changed; thus, unless and until the mechanistic reasons for the value of RDW are elucidated, a therapeutic imperative associated with its management cannot be derived and tested .
RDW is easily measured, standardized and typically reported with complete blood count values at no additional cost; its independent predictive value for various CV events makes further research of other ‘at-risk populations’ for CV events imperative .
The aim of this study was to assess the value of RDW among CHF patients when compared to local reference values and if it could be used as diagnosis value in addition to other clinical variables among inpatients with CHF.
The study was conducted at Hiwot Fana Specialized University Hospital with Cross-sectional study design. Convenient sampling technique was used among confirmed CHF patients who visits Hiwot Fana Specialized University Hospital from September 2016 to March 2017 . Accordingly all CHF patients who was admitted in the Hospital within the study period was included in the study. The study subjects were interviewed using structured questionnaires on socio-demographic characteristics, risk factors and other baseline information. Baseline clinical characteristics such as CHF stage, Alcohol, Chat chewing habit were also collected using a checklist.
Sample was collected during admission and all hematological parameters were determined using the Cell Dyn Ruby hematology analyzer, Abbott, USA. Local reference range was performed for all hematological parameters by using control group (using 77 local reference group which was apparently healthy after assessing physical examination, medical history including recent hospitalization and chronic disease history. Besides this; stool examination, screening for typhoid, typhus and malaria were performed for the control group) to compare with confirmed CHF patients hematological parameters based on central 95% of the reference population of subjects (Table 2). By definition, 5% of all results from “healthy” people will fall outside of the reported RI and, as such, will be flagged as being “abnormal” . The blood sample was collected, labeled, transported and stored in a proper manner to ensure sample integrity. During testing, the trained laboratory personnel was adhered strictly to the Standard Operating Procedures (SOP) and manufacturer instruction manual in each procedure to ensure the data quality for laboratory tests.
Data collected was entered into Epi data and exported to SPSS version 20 for analysis. The one-sample T-test was used to compare RDW among CHF patients and control groups. Independent T-test also used to compare RDW while Hgb < 12 g/dl and Hgb > 12 g/dl. Bivariate analysis was performed to check whether the RDW has association with other hematological parameter. The multivariate model was adjusted for potential confounding variables that show a significant association with RDW bivariate analysis. Statistical significance was set at p < .05.
The study was conducted among 99 CHF patients and 82 control group, but after excluding incomplete data the final study participants were 87 for CHF patients and 77 control group.
The mean age of the study participants for CHF patients were 42.84 (standard deviation + 18.32years) in years, with range 16 to 90 years. More than 76%, 59% and 86% were rural community, female study participants and married study participants, respectively (Table1).
Table 1: Sociodemographic variables among confirmed CHF patients at Hiwot Fana Specialized University Hospital, Harar, Ethiopia from September 2016 to March 2017.
Table 2: Red cell and platelet parameters among control group (for local reference) from September 2016 to March 2017 at Hiwot Fana Specialized University Hospital, Harar, Ethiopia by using Cell Dyn Ruby Correlation of RDW with hematological parameters.
RDW among confirmed CHF patients: The RDW ranged from 12.60 to 36.30% (median 17.6%), and only twelve CHF patients (13.2%) had RDW value within the local normal range (11–14.4%). Accordingly the RDW determined was 18.42 ± 3.89% (mean ± SD), n=87 after excluding the outlier and more than 86% of RDW determined were out of local reference range (11–14.4%) (Table2). One-sample t-test was used to compare the CHF patient and local reference group RDW. There was significant difference in scores for CHF patient RDW (M = 18.86, SD = 4.76 n = 87) and RDW of the local reference group (M = 12.35, SD = .80; p = .000, two-tailed n = 77). As it has been shown on the figure there was a huge difference between the CHF patients’ and the control or local reference ranges RDW (Figure1).
Figure 1: Compares RDW of CHF patient and local reference group among confirmed CHF Patient from September 2016 to March 2017 at Hiwot Fana Hospital, Harar, Ethiopia.
Correlation of RDW with Hematological Parameters
This study also tried to analysis the correlation of RDW with other parameters both hematological and non-hematological. Bivariate and multivariate regression analysis were conducted to check whether RDW has correlation with other variables, accordingly the RDW has correlation with MCHC, HGB and PCT measurement or parameters among confirmed CHF patients (Table 3). From this study, as it has shown in the figure 2 RDW was high when MCHC was lower than the local reference range (31.5 to 34.5 pg/l) and it seems MCHC was sensitive to measure RDW parameter (Table 3, Figure 2). The other interesting finding of this study was the relation between RDW and PCT (0.07 to 0.24) which was inversely related with each other among confirmed CHF patients (Table 3, Figure 3).
Table 3: Multivariate regression analysis for RDW and other related parameters among confirmed CHF patients from September 2016 to March 2017 at Hiwot Fana Specialized University Hospital, Harar, Ethiopia.
Figure 2: Compare distribution of RDW and MCHC of CHF patient based on local reference range for labeling line among confirmed CHF patient from September 2016 to march 2017 at Hiwot Fana Hospital, Harar, Ethiopia.
Figure 3: Compare Distribution of RDW and PCT of CHF Patient based on local reference range for labeling line among confirmed CHF patient from September 2016 to march 2017 at Hiwot Fana Hospital, Harar, Ethiopia.
The other parameter correlated with RDW was Hgb (12 to 17.2 g/dl) which was also inversely related with RDW (Table 3). To compare the RDW for Hgb < 12 g/dl and > 12 g/dl an independent-samples t-test was used. From the finding its known there was significant difference in scores for Hgb < 12 g/dl (M = 19.56, SD = 4.96) and Hgb >12 g/dl (M = 17.17, SD = 3.84; t (85) = -2.45, p = .030, two-tailed).
Anemia among CHF patients: Hemoglobin, Mean cell concentration (MCH), Mean corpuscular hemoglobin concentration (MCHC) and hematocrit among patient was 9.95 ± 3.9 g/dl, 25 ± 4.26 pg, 29.97 ± 2.47 pg/l and 33.24 ± 13.11% 6%, respectively. The Hgb range among the patient was 0.72 to 20.90 g/dl, from which 70.2% of the patient had less than local normal reference range for hemoglobin (12–17.2 g/dl), although the reference range given by Cell Dyn Ruby was 12.9–14.23 g/dl (Table 2). More than 70% of the CHF patient have anemia (< 12 g/dl) according to this local reference range and this reference value agree with least amount of Hgb for non-pregnant women (< 12g/dl) for diagnosis of anemia by World Health Organization (WHO, 2011). From those anemic cases the most prevalence types of anemia was normocytic normochromic (50.82%), followed by microcytic hypochromic (34.42%) and macrocytic normochromic (14.75%) based on the local reference value for MCV (79.3–97.1 fl).
The RDW is a readily available and inexpensive test for patients with CHF. However; the mechanisms of the associations between CVDs and RDW are unclear because increased RDW is associated with several CVDs with different etiologies . The intention of this study was to assess the value of RDW and other hematological parameters among confirmed CHF patient.
RDW Among Confirmed CHF Patients
More than 86% of confirmed CHF patients had RDW greater than local reference value or control group which was conducted to verify the reference value given by hematology analyzer. One-sample t-test was used to compare the CHF patients and control groups RWD, revealed significant difference in scores for CHF patient RDW (M = 18.86, SD = 4.76) and RWD of the control (M = 12.35, SD = 0.80; p = 0.000, two-tailed). The RDW determined was 18.86 ± 4.76% (mean ± SD) which ranged from 12.60 to 36.30% (median 17.6%), whereas the local reference value for RDW was 11–14.4%. This finding was consistent with the study finding by , in which RDW was 14.1% to 35.1% (median 18%) among advanced stage heart failure. High RDW was reported in most studies conducted among CHF patients although the magnitude and the study design was different [2–11].
Although it’s beyond this study to discuss pathophysiology of why RDW increased among CHF patients, the reason usually RDW increased among CHF patients are because of it may represent an integrative measure of multiple pathologic processes. In HF such as nutritional deficiencies, renal dysfunction, hepatic congestion and inflammatory stress (where different Inflammatory cytokines presented), explaining its association with clinical outcomes . Iron deficiency, B12 or folate deficiency, liver disease, malnutrition, occult colon cancer, and neoplastic metastases to bone marrow and qualitative hemoglobin abnormality, increased red cell destruction and ineffective red cell production are some of conditions causes RDW increased .
Correlation (Predictors) of RDW with Other Hematological Parameters
The correlation of RDW with other variables conducted by bivariate and multivariate regression analysis showed RDW has correlation with MCHC, HGB and PCT measurement or parameters among confirmed CHF patients (Table 3). With this study RDW had correlation with MCHC parameter (Beta -0.372 p = 0.000 95% CI -0.893 to -0.285), in which MCHC inversely related with RDW. This finding was consistent with study conducted by  which revealed increased RDW was associated with decreased erythrocytes and MCHC . The MCHC is expressed in grams of hemoglobin per deciliter of packed red blood cells (measures the amount hemoglobin per unit blood). This represents measurement of Hgb or the ratio of hemoglobin mass to the volume of red cells. This result indicated when the ratio of hemoglobin mass to the volume of red cells decreased RDW was increased among CHF patients.
The RDW had also correlation with PCT (Beta -0.213, p = 0.044, 95% CI -26.62 to -0.40) and PCT was again inversely related with RDW among confirmed CHF patients. Although there was limited study regards to PCT and RDW correlation, the study conducted by Borne Y et al.  was inconsistent with our finding which revealed increased RDW was associated with increased mean corpuscular volume (MCV), leucocyte and platelet counts among heart failure. The PCT provides reliable data regarding total platelet mass and indicates the number of circulating platelets in a unit volume of blood, analogous to the hematocrit for erythrocytes [12,14] according to this finding when a number of circulating platelet per unit of blood decreased the RDW was increased.
The RDW had correlation with Hgb (Beta= -0.212 p = 0.044 95% CI -0.433 to -0.006), it was also inversely related with RDW measurement. An independent-samples t-test was used to compare the RDW for Hgb < 12 g/dl and ≥ 12 g/dl. There was significant difference in scores for Hgb < 12 g/dl (M = 19.56, SD = 4.96) and Hgb ≥ 12 g/dl (M = 17.17, SD = 3.84; t (85) = -2.45, p = 0.030, two-tailed). The magnitude of the differences in the means (mean difference = -2.41, 95% CI: -4.580 to -0.246) was moderate (eta squared = 0.066). This finding was consistent with the study conducted by Tonelli M et al. , that revealed patients with higher RDW levels had lower levels of hemoglobin . Other study by Tseliou E et al. , revealed both RDW and hemoglobin concentration important predictors of mortality among patients hospitalized with chronic heart failure . Besides this, study conducted among CHF patients by Dai Y et al, revealed Hgb is independent predictors of RDW . Anemia increased because of low Hgb among CHF patients and RDW was increased in those patients because low Hgb causes RBC to have different size (anisocytosis), that’s why hemoglobin was inversely related with RDW.
Anemia among CHF Patients
By this study it has been revealed 70.2% of the CHF patients had anemia. It can be classified based on morphology or mean cell volume, accordingly the anemia that was common among CHF patients by this study was normocytic normochromic anemia (50.82%), followed by microcytic hypochromic (34.42%) and macrocytic normochromic (14.75%) based on the local reference value for MCV (79.3–97.1) . The prevalence of anemia found by this study was higher than studies conducted by [15,11], which revealed the prevalence of anemia 60%, 57% and 42% among heart failure patients, respectively [15,18]. This variation might be due to reference range used by those studies differ from this study which used local reference range (control group) which was specific for study population. Normocytic normochromic anemia was more prevalent (50.82%) types of anemia which indicated anemia sources might be due to RBC loss (either by destruction or bleeding) or low production. Low RBC production might be related to EPO resistance, inadequate bone marrow response to EPO, leading to an impaired erythropoiesis, which is associated with morbidity and mortality in acquired heart disease .
Limitation of The Study
This study was cross-sectional study, although we planned to apply longitudinal prospective design due to scarcity of budget and short period of time allowed for the study we shifted into cross-sectional study, so we recommend further study using prospective study design to follow the patients and measure RDW frequently parallel to different outcomes.
More than 90% of the RDW determined among confirmed CHF patient was out of local normal reference range (11–14.4%). Red Distribution Width ranged from 12.60 to 36.30% (median 17.6%) and was correlated with Hgb (Beta = -0.212 p = 0.044 95% CI -0.433 to -0.006), MCHC (Beta -0.213, p = 0.044, 95% CI -26.62 to -0.40) and PCT (Beta -0.213, p = 0.044, 95% CI -26.62 to -0.40). Anemia was prevalent (70.2%) among CHF patient and the normocytic normochromic types of anemia was more prevalent than the other types of anemia.
The RDW was high among CHF patients based on local reference range, so if properly managed it could be used for diagnosis and prognosis purpose among CHF patients in the future even could be included in protocol for diagnosis of CHF. For CHF patients, screening for disease such as anemia and evaluation of iron, EPO, vitamin B12, folic acid and nutritional status may be valuable for better diagnosis, monitoring and management CHF.
Conflict of interest
The authors declare that they have no competing interests.
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Copyright: © 2017 Urgessa F, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.