Prevalence and associated factors of anemia among people with cancer in ACSH, Tigray, Ethiopia

doi:10.21203/rs.3.rs-3208295/v1

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Prevalence and associated factors of anemia among people with cancer in ACSH, Tigray, Ethiopia

https://doi.org/10.21203/rs.3.rs-3208295/v1

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Background: anemia is becoming a public health problem particularly among people suffering from different types of cancer.

Objective: the aim of this study was to assess the prevalence and associated factors of anemia among people with cancer.

Methods: an institution based cross-sectional study was conducted from January to June 2020 in ACSH, Tigray, Ethiopia. Medical records were systematically reviewed to get demographic and clinical characteristics of 72 study subjects. Data were entered to SPSSv25 and descriptive analysis, logistic regression, independent sample T test and ANOVA were used for analysis.

Results: about 45.8% of study subjects with different types of cancer were found to have anemia. Unemployment (OR=2.167; 95%CI: 1.093, 4.294; p=0.027), rural residence (OR = 3.750; 95%CI: 1.245, 11.299; p= 0.019), advanced stages of cancer (OR = 10.771; 95%CI: 3.580, 32.405; p= 0.000), duration of cancer (OR=3.542; 95%CI: 1.289, 9.728; p=0.014) and higher (5-8) cycles of chemotherapy (OR = 3.000; 95%CI: 1.090, 8.254; p=0.033) were variables found to have statistically significant association with anemia.

Conclusion: anemia is a common complication in patients with different types of cancer. Occupation, residence, duration of cancer, stage of caner, chemotherapy, and cycles of chemotherapy significantly increased the prevalence of anemia in cancer patients.

Anemia

Prevalence of anemia

Risk factors of anemia

Cancer

Chemotherapy

Anemia related to cancer is a public health problem, and has multifactorial pathogenesis (1). Reviewed reports are showing that anemia is a common comorbidity to cancer patients. According to the reviewed literatures, the prevalence of anemia in patients with solid cancer ranges from 23% in Ethiopia to 68% in United States (2–7). Gaspar et al reviewed that the prevalence of anemia in patients treated for malignancies range from 40–64% (8). The European Cancer Anemia Survey (ECAS) reported that 39.3% of prospectively evaluated cancer patients were found to be anemic (5), and around 63.2% of Chinese with solid cancer were presented with anemia (6). Even a higher prevalence rate, 68%, was reported from an intensive care unit (ICU) in United State (US) comprehensive cancer center (7). In India, Sharma et al (9) found that 46.7% of 116 women with breast cancer were detected to have mild to moderate anemia at baseline analysis; while, all these women (n = 116) had developed anemia during the course of chemotherapy. In Saudi, the prevalence of anemia among 320 patients with solid cancer was 44.1% and patients with colorectal (56.8%) and female genital cancer (43.8%) demonstrated higher anemia prevalence (4). Another study also reported a 42.4% of patients with gastric cancer had experienced anemia in at least once during the five years after gastrectomy (10). Similarly, studies from Africa are revealing high prevalence of anemia among cancer patients. In Kenya, about 38.6% of women with cervical cancer were reported to present with severe anemia (11). In the same way, anemia is highly prevalent in Ethiopia (3, 12). The prevalence ranges from 23–54.8% across different types of solid tumor (3, 13), and the prevalence ranges from 21.7% in patients with breast cancer to 50.95% in patients with cervical cancer (12).

Different variables had been reported to be correlated with anemia in cancer patients. Reviewed evidences show that variables like types of cancer, administration of chemotherapy and chemo-radiation, number of chemotherapy, types of chemotherapy, stage of cancer, use of substances and having comorbidities were significantly associated to cancer related anemia (2, 6, 12, 14).

Anemia in cancer patients has several etiologic factors (1). It can occur as a result of cytokines imbalance (15), or as anemia of chronic diseases (16), as nutritional deficiencies (17, 18), due to the administration of chemotherapy (8) and/or due the tumor (cancer) itself (14, 19). Myelotoxicity is a common adverse effect experienced by cancer patients receiving chemotherapy or radiotherapy, and this adverse effect presents as anemia, neutropenia and/or thrombocytopenia (19). Based on a study conducted in Shaukat Khanum Memorial Cancer Hospital and Research Centre, chronic diseases were a common causes of cancer related anemia accounting to 33.1% followed by 27.17% of anemia caused by bone involvements (16). Apro et al reported that from 32 to 60% of cancer related anemia are iron deficiency (20). Anemia also occurs as a result of cancer treatments. For example, Aynalem et al (21) reported that the hemoglobin and hematocrit count of patients with breast cancer were significantly reduced after the initiation of cancer treatments.

Although the prevalence of anemia among people with cancer is high, only less proportion of cancer patients get appropriate diagnosis and treatment of anemia (5, 22, 23). If untreated, anemia could have additive consequences to cancer patients. For example, untreated anemia may compromise the quality of life (QoL) and causes fatigue in cancer patients (22, 24, 25).For example, a cross-sectional study in Ethiopia confirmed that anemic cancer patients had increased risk of experiencing fatigue compared to patients without anemia (13). In addition, Clarke and Pallister (14)had reviewed that around 65% of cancer patients have an overall increased risk of death related to anemia. Likewise, a study conducted in Ethiopia had demonstrated an increased risk of anemia related deaths in patients with cervical cancer (26).

The diagnosis of anemia in cancer patients can be established through detailed clinical history and physical examination, supported with peripheral blood morphology and reticulocyte count. However; standard approaches should be used in the diagnosis of unexplained anemia, and serum iron profile and bone marrow examination may be required in difficult cases (8).

Different studies have reported different types of treatment options for cancer-related anemia. For instance, administration of erythropoiesis stimulating agents (ESA), transfusion of packed red blood–cells, and administration of intravenous (IV) iron are mostly reported treatment options(20, 27–29). Spivak et al (30) on his review had concluded that ESAs have efficiently improved erythropoiesis and reduced the need for red blood transfusion in anemic cancer patients. Similarly, Bryer and Henry (31) reviewed that the use of intravenous iron and/or ESA had reduced the need for blood transfusion in the treatment of cancer-related anemia. Another review (32) also recognized that anemic cancer patients demonstrated superior response to ESAs combined with intravenous iron, and revealed that iron therapy alone is useful option in the treatment of mild and absolute iron deficiency (AID) anemia. Epoetin alfa was also reported as a choice of treatment. Epoetin alfa had been confirmed to increase hemoglobin level and improve poor quality of life of cancer patients with anemia (33–35).

Reviewed literatures indicated that anemia in cancer patients is highly prevalent and is almost similarly distributed across the world(2, 3, 5, 10, 11, 26).Although Ethiopia is multi-ethnic and multi-cultural country, studies conducted in this country are more specific to cervical and breast cancers and limited to Addis Ababa and Amahar regional states. This indicates that there is lack of preliminary evidences on the prevalence and associated factors of anemia among patients with solid cancer in the country, particularly in Tigray regional state. Lack of robust evidences may affect the quality of care provided to cancer patients with anemia. So, this study had tried to fill this knowledge gap. This study had mainly tried to determine the prevalence and associated risk factors of anemia among patients with solid cancer in Tigray, northern Ethiopia.

An institution based cross-sectional study was conducted at Ayder Comprehensive Specialized Hospital which is located in Mekelle, the capital city of Tigray. The study was conducted from January to June 2020. Sample size were calculated using Epi-info software to be N=72, with an assumptions of 95% level of confidence, 80% of power, and the ratio of exposure to chemotherapy among cancer patients to be 1:1. Study subjects who visit the oncology clinic during the study period were systematically selected based on the following eligibility criteria, then their medical records were reviewed to get demographic and clinical characteristics:-

Inclusion criteria

All adult cancer patients aged 18 years and above

Exclusion criteria

Critically ill
Those who were treated for hematologic problems in the past 3 months
Pregnant women
Malaria in the last 2 weeks
Bleeding history in the last 2 weeks
Patients with Aplastic anemia
Patients with other chronic co-morbidities
Other therapies that suppress bone marrow

Data collection Tools and procedures

Standardized semi-structured pretested questionnaire was used during face-to-face interview and review of documented medical records. Study subjects were interviewed for eligibility and to get Socio-demographic data. Their medical records were reviewed to collect medical characteristics like duration of disease, type and stage of cancer, type of medication, duration of treatment and hematologic indices (level of Hb) were taken from patients’ medical records.

Data quality control

To keep the quality and reproducibility of the data, the data collectors were trained on the objective of the study and every procedure the data collection. Validity of the questionnaire was maintained by performing pretest in 5% of the sample size and necessary corrections were done on the questionnaire after pretest. Data from pretested subjects was not included in the actual study result. Each completed questionnaire was checked each day by the principal investigator to ascertain that all the questions were answered consistently and incomplete data was discarded and/or corrected. The data was entered into SPSS version 25 statistical software and rechecked carefully.

Data Analysis

Data was manually checked for its clarity and completeness and then coded, cleaned and entered in to SPSS version 25 software. Descriptive statistics, logistic regression, independent-samples T test and one way ANOVA models were used to describe data, identify associations of anemia and categorical variables, to compare mean differences in hemoglobin level between variables at p-value less than 0.05.

Ethical Consideration

Ethical clearance and approval later were obtained from Research and Ethical Review Committee of College of Health Sciences of Addis Ababa University. The proposal was further evaluated in light of the ethical standards and permission letter was obtained from Ayder Comprehensive Specialized Hospital. The study participants were briefed on the objective and procedures of the study. Thereafter, informed consent was obtained from volunteers. No personal identifiers were attached/recorded to the interview. The data provided was kept strictly confidential by using only code numbers.

Demographic descriptions

From the total study subjects participated in the study (N = 72) majority (54.2%) were males and have an average age of 47 years old (Std. = 15 Years). Half of the study subjects were secondary or above in their educational level and about 26.4% were rural resident and around 47.2% have regular income (See Table-1 for detail information).

Description of hemoglobin (Hb = hg/dL)

The mean hemoglobin count for the total study subjects (N = 72) were 12.126 g/dL ± 1.955 g/dL and statistically significant mean difference in hemoglobin count was observed on variables like occupation, residence, duration of cancer, stage of cancer, and chemotherapy use (see Table-2 below). From the total chemotherapy users, study subjects those who have high number cycles (cycles of 5 to 8) of chemotherapy demonstrated statistically significant difference in mean in the hemoglobin (Hb) count than study subjects who take low cycles (cycles of 1 to 4) of chemotherapy or than those who do not take chemotherapy at all (see Table-2).

Description of Anemia, Cancer and Chemotherapy

Table-3 presents the description of anemia, Cancer and Chemotherapy. In this study, around 45.8% (n = 33) of the total study subjects (N = 72) were found to have mild to severe range of anemia. Anorectal/Colorectal cancer accounts for 27.8% and lung cancer for 23.9% of cancers of the total study subjects with cancer. Majority of study subjects have either Stage-II or Stage-III cancer, 33.3% have stage-II and 30.6% have stage-III. Half of the study subjects were on chemotherapy and around 37.5% of study subjects took combined chemotherapy (See Table-2 for details).

Anemia and its determinant factors

Table-4 show what factors correlate to anemia. From the Table, we can understand that variables like employment, residence, duration of cancer, advanced stage of cancer, chemotherapy use, and use of high cycles of chemotherapy are independent predictors of anemia among study subjects with cancer (See Table-4).

According to the present study more than half (54.2%) of the study subjects were male with an average age of 47 (± 15) years. An overall mean hemoglobin count of the total study subjects were 12.13g/dL (± 1.96g/dL). According to the findings of the present study, study subjects those who were unemployed, with rural residence, have cancer for 6 months or more, who had advanced stages of cancer (stages III & IV), those who were on chemotherapy, and study subjects who have high cycles of chemotherapy demonstrated significantly lower hemoglobin count than their counter parts. Majority of study subjects were diagnosed as having stage-II and stage-III cancers. Half of the study subjects were on chemotherapy and 37.5% of them took combined chemotherapy. Based on the findings of this study, the prevalence of anemia among patients with different types of tumors was 45.8%. This finding is consistent with the prevalence rates reported by Muthanna et al (2) and Almehmadi et al (4). However; this is lower to reports in Ludwig et al, Cheng et al and Cardenas-Turanzas et al (5–7), and it is higher to the prevalence in Ethiopia reported by Kifle et al (3). According to the present study; around 68.4% of unemployed cancer patients developed anemia, whereas only 20.6% of employed cancer patients were anemic. Logistic regression confirmed that unemployed study subjects with cancer were 8.36 times more likely to develop anemia than employed. Haddad et al on his review reported that an increased income can reduce under-nutrition (36). So, the variations could be explained by the fact that unemployed cancer patients could have malnutrition related anemia (29) since they did not have income to follow balanced dietary habits. This study also stated that about 78.9% of study subjects with rural residence were anemic, while only 34.0% of rural residents developed anemia. Logistic regression has recognized that cancer patients with rural residence were 7.29 times at risk to develop anemia than urban residents. On the other hand, findings of this study have revealed that 64.0% of study subjects with cancer duration of ≥ 6 months developed anemia, but only 36.2% of those who have cancer duration < 6 months developed anemia. This result was significant on regression analysis that indicated patients with cancer duration ≥ 6 months were 3.54 times more likely to develop anemia than those who have less duration of cancer. Sudies that assess anemia in cancer patients and its association with residence of cancer patients and duration of cancer is in scarcity and comparison of findings of the present study to external studies become so difficult. About 72.2% of study subjects with advanced cancer (cancer stages III & IV) were anemic in this study when compared to 19.4% of those with less stages of cancer (cancer stages I & II). This was also significant on regression; patients with advanced cancer were 10.77 times at increased risk of developing anemia than their counter parts. Similarly, results of this study established that 58.3% of study subjects who take chemotherapy and 75.5% of subjects who had 5 to 8 cycles of chemotherapy have developed anemia, whereas only 33.3% of those who did not take chemotherapy and 37.5% of those who had 1 to 4 cycles of chemotherapy developed anemia respectively. And analysis of logistic regression indicated that study subjects who take chemotherapy and those who had 5 to 8 cycles of chemotherapy were 2.80 and 6.00 times more likely to develop anemia than their counter parts respectively. Myelosuppressive effect of the cancer itself and its chemotherapy could be suggested explanation for the variations in cancer stages, chemotherapy use and the cycles of chemotherapy (22, 24).

Results of the present study allowed the identification of prevalence of anemia and discriminatory predictors contributing to the risk of having anemia. According to findings of the present study, anemia is a common complication in patients with different types of cancer in Tigray, Ethiopia. Occupation, residence, duration and stage of cancer, chemotherapy and cycles of chemotherapy were demographic and clinical factors that significantly increased the prevalence of anemia in cancer patients in which farther studies with large sample size are recommended to duplicate findings of the present study.

Acknowledgments

We wish to express our sincere gratitude to all who buttress us in any way at all to complete this study:-

Addis Ababa University, College of Health Science, department of medical physiology for the financial aid, reviewing and providing ethical clearance
Mekelle University Comprehensive Specialized Hospital for allowing the study to be carried at.
All friends and colleagues who encouraged and supported procedures of this study.

We declare that "Prevalence and associated factors of anemia among people with cancer in ACSH, Tigray, Ethiopia" is our own work and all sources that have been used or quoted in this work are well indicated and acknowledged by means of complete references and this work was not submitted for any reasons in any institutions.

Ethical Aproval

Ethical clearance was obtained from Research and Ethical Review Committee of the department Physiology, College of Health Science, Addis Abeba University.

Computing Interest

We researchers declare that we did not have any computing interest.

Author's Contribution

Woldemariam AG contributes on the preparation of the manuscript. Tsehaye A caried out the overall study, Wendyefraw M particpated as advisor and all other authors have participated in the study equally.

Funding: Not applicable

Avialability of data and materials: Not applicable

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Table-1: Socio-demographic description of study subjects at ACSH, Tigray, Ethiopia (N=72).

No	Variables		Frequency	Per. (%)
No	Variables		Frequency	Per. (%)
1	Age	Mean=47
		Std. = 15
		Skewness = -.326
		Kurtosis = -1.073
2	Sex	Female	33	45.8
2	Sex	Male	39	54.2
3	Marriage	Married	57	179.2
		Single	13	18.
		Widowed	2	2.8
4	Religion	Orthodox	68	94.4
4	Religion	Muslim	4	5.6
5	Education	Secondary or above	36	50.0
5	Education	Primary or below	36	50.0
6	Residence	Urban	53	73.6
6	Residence	Rural	19	26.4
7	Occupation	Employed	34	47.2
7	Occupation	Unemployed	38	52.8
8	Regular income	Yes	34	47.2
8	Regular income	No	38	52.8

Table-2: Comparison of hemoglobin count among study subjects at ACSH, Tigray, Ethiopia (N=72).

Variables		Mean in hg/dL	Mean difference	95% CI		P=value
				Lower	Upper
Occupation	Employed	13.2971	2.21811	1.45649	2.97973	0.000
	Unemployed	11.0789
Residence	Urban	12.7566	2.38818	1.47839	3.29797	0.000
	Rural	10.3684
Duration of cancer	< 6 month	12.8804	2.08813	1.21746	2.95879	0.000
	≥ 6 month	10.7923
Stage of cancer	Stages I&II	13.0500	1.84722	1.03162	2.66283	0.000
	Stages III & IV	11.2028
Chemotherapy use	No	12.9944	1.73611	0.90726	2.56496	0.000
	Yes	11.2583
Cycles of chemotherapy	No	12.9944	----	---	---	0.000
	1 to 4 cycles	12.2062
	5 to 8 cycles	10.5000

Table-3: Description of Anemia, Cancer and use of chemotherapy among study subjects at ACSH, Tigray, Ethiopia (N=72).

No	Variables		Frequency	Per. (%)
1	Presence of Anemia	No	39	54.2
1	Presence of Anemia	Yes	33	45.8
2	Scale of Anemia	Normal	39	54.2
		Mild	14	19.4
		Moderate/Severe	19	26.4
3	Types of cancer	Anorectal/ Colorectal Cancer	20	27.8
		Lung Cancer	10	13.9
		Oral/laryngeal/Nasopharyngeal Cancer	7	9.7
		Sarcoma	9	12.5
		Breast cancer	7	9.7
		Bladder cancer	6	8.3
		Other types of cancer	13	18.1
4	Stages of Cancer	Stage-I	12	16.7
		Stage-II	24	33.3
		Stage-III	22	30.6
		Stage-IV	14	19.4
5	Duration of Cancer	<6 months	47	65.3
5	Duration of Cancer	≥ 6 months	25	34.7
6	Chemotherapy	No	36	50.0
6	Chemotherapy	Yes	36	50.0
7	Types of chemotherapy	Antimetabolites	2	2.8
		Antimitotic agents	4	5.6
		Combined¹	11	15.3
		Double Alkylators	3	4.2
		Combined²	5	6.9
		Combined³	8	11.1
		Combined⁴	3	4.2
8	Cycles of Chemotherapy	No	50	50.0
		1-4 Cycles	16	22.2
		5-8 Cycles	20	27.8

Key: 1 = Alkylators + Antimetabolites; 2 = Alkylators + Antitumor Antibiotics; 3 = Alkylators and antimitotic agents; 4 = Alkylators + Antimitotic agents + Antitumor Antibiotics.

Table-4: Factors associated with Anemia among study subjects with cancer at ACSH, Tigray, Ethiopia.

Variables		Anemia				AOR	95%CI	P - Value
		No		Yes
		No	%	No	%
Sex	Male	23	59	16	41	1	1	1
Sex	Female	16	48.5	17	51.5	1.527	0.600, 3.888	0.374
Age	18-31	9	47.4	10	52.6	1	1	1
	32-45	6	75.0	2	25.0	0.300	0.048, 1.882	0.199
	46-59	15	62.5	9	37.5	0.540	0.159, 1.833	0.323
	60-74	9	42.9	12	57.1	1.200	0.344, 4.181	0.775
Marriage	Married	31	54.4	26	45.6	1	1	1
Marriage	Single^*	8	53.3	7	46.7	1.043	.334, 3.264	0.942
Religion	Orthodox	36	52.9	32	47.1	2.667	0.264, 26.938	0.406
Religion	Muslim	3	75.0	1	25.0	1	1	1
Education	≥ 2^nryschool	21	58.3	15	41.7	1	1	1
Education	≥ 1^mry school	18	50	18	50	1.400	0.552, 3.550	0.478
Occupation	Employed	27	79.4	7	20.6	1	1	1
Occupation	Unemployed	12	31.6	26	68.4	8.357	2.848, 24.524	0.000
Residence	Urban	35	66	18	34	1	1	1
Residence	Rural	4	21.1	15	78.9	7.292	2.108, 25.218	0.002
Duration of cancer	< 6 months	30	63.8	17	36.2	1	1	1
Duration of cancer	≥ 6 months	9	36.0	16	64.0	3.542	1.289, 9.728	0.014
Stages of cancer	Stage-I & II	29	80.6	7	19.4	1	1	1
Stages of cancer	Stage-III & IV	10	27.8	26	72.2	10.771	3.580, 32.405	0.000
Chemotherapy	No	24	66.7	12	33.3	1	1	1
Chemotherapy	Yes	15	41.7	21	58.3	2.800	1.073, 7.304	0.035
Chemotherapy	No Chemotherapy	24	66.7	12	33.3	1	1	1
	Cycles 1-4	10	62.5	6	37.5	1.200	0.352, 4.092	0.771
	Cycles 5-8	5	25.0	15	75.5	6.000	1.760, 20.458	0.004

No competing interests reported.

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Prevalence and associated factors of anemia among people with cancer in ACSH, Tigray, Ethiopia

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Abstract

Introduction

Methods and Materials

Results

Demographic descriptions

Description of hemoglobin (Hb = hg/dL)

Description of Anemia, Cancer and Chemotherapy

Anemia and its determinant factors

Discussion

Conclusion

Declarations

References

Tables

Additional Declarations

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