|Year : 2022 | Volume
| Issue : 1 | Page : 38-42
Gender differences in the complications of sickle cell anemia
Angela O Ugwu
Department of Haematology and Immunology, College of Medicine, University of Nigeria/University of Nigeria Teaching Hospital Ituku/Ozalla, Enugu State, Nigeria
|Date of Submission||11-Apr-2021|
|Date of Decision||02-May-2021|
|Date of Acceptance||18-May-2021|
|Date of Web Publication||3-Dec-2021|
Angela O Ugwu
Department of Haematology and Immunology, College of Medicine, University of Nigeria/University of Nigeria Teaching Hospital Ituku/Ozalla, Enugu State.
Source of Support: None, Conflict of Interest: None
Background: The clinical severity of sickle cell anemia (SCA) varies from one individual to another. Several factors, including genetic predisposition, environmental and social factors, are known to modify the clinical presentation and complications of SCA but not much is known about the influence of gender. Objective: This study aims at determining the gender differences in the pattern of SCA complications in Enugu, Nigeria. Materials and Methods: This is a retrospective analysis of clinical and laboratory data from the folders of patients with SCA at the University of Nigeria Teaching Hospital Enugu, Nigeria between February 2008 and February 2014. A total of 248 folders comprising 151 males and 97 females were retrieved. Data on the age, sex, hematological parameters, number of complications, and frequency of SCA crises were extracted and analyzed. Only the case files of adult patients with SCA were investigated. Results: The median age of the participants was 25 (IQR = 22–30) years. The male to female ratio was 1.5:1. A total of 182 out of 248 (73.4%) cases reviewed had one form of complication or the other. Sickle cell leg ulcer was the most common complication seen among the cases (50/182 [27.5%]), followed by avascular necrosis (AVN) (28/182 [15.4%]). The mean frequency of crises was not different between the male and female genders (15.00 ± 9.01 vs. 9.8 ± 6.97; P = 0.293). However, the male gender had more complications than the female gender (116/151 [73.9%] vs. 116/151 [73.9%]; odds ratio [OR] = 2.13; 95% confidence interval [CI] = 1.2–3.7; P = 0.007). Conclusion: The male gender is twice more likely to develop complications of SCA and, thus, are more likely to have more morbidity from this condition.
Keywords: Complications, sickle cell anaemia, sickle leg ulcer, vaso-occlusive crises
|How to cite this article:|
Ugwu AO. Gender differences in the complications of sickle cell anemia. Int J Med Health Dev 2022;27:38-42
| Introduction|| |
Sickle cell disease (SCD) is a group of genetic disorders that affects the hemoglobin molecules of red blood cells. Individuals who have this disease have abnormal hemoglobin molecules termed hemoglobin S (HbS). This disorder is inherited in a recessive manner, which means that an individual will require the presence of two abnormal hemoglobin molecules, of which one must be HbS in order to manifest the disease. Some examples of SCD include SCA, Sickle Hemoglobin-C Disease (SC), Sickle Beta-Plus Thalassemia, and Sickle Beta-Zero Thalassemia.
There is a point mutation at position 6 of the beta globin gene, which results in the substitution of glutamic acid with Valine. This substitution leads to a change in the physicochemical properties of the hemoglobin. A host of factors, including infections, hypoxia, dehydration, and physical stress, cause polymerization of deoxygenated HbS, rigidity of the red cells, and increased expression of the adhesion molecules that enhance the adhesiveness of red cells to one another, to the endothelium, and to other blood cells, including white blood cells and platelets., Central to the pathophysiology of SCD are polymerization of HbS, vaso-occlusion of small-sized blood vessels, and hemolysis. Repeated episodes of these events culminate in the complications that are seen in SCD.
The clinical signs and symptoms of SCD manifest at about five to six months of life, with the waning of the fetal hemoglobin. These individuals often have exacerbation of their clinical signs and symptoms termed “sickle cell crises.” The sickle cell crises include vaso-occlusive crisis, aplastic crisis, and sequestration crisis. In between these acute episodes of crises, they are in a state of relative well-being termed the “steady state.”
The most common form of SCD is the homozygous form, HbSS, also called SCA. The SCA affects every organ system in the body. The clinical effects of SCD worsen with increasing age. These patients develop multiple complications that culminate in end organ damage from sustained hemolysis and vaso-occlusive events. There is an inverse relationship between quality of life (QOL) of patients with SCD and the frequency of crises they experience. The QOL worsens with an increasing frequency of acute events and with an increase in the number of complications. These complications could be acute or chronic (lasting more than 3 months) The acute complications include recurrent painful crisis, acute chest syndrome, stroke, hyperhemolysis, and infections such as lobar pneumonia. The chronic complications include but are not limited to pulmonary hypertension, nephropathy, AVN of the bones, retinopathy, chronic osteomyelitis, and sickle leg ulcers (SLU). In order to prevent many of these complications, including stroke, the patients with SCD are chronically transfused with resultant alloimmunization as one of the complications. Blood transfusion aims at reducing the percentage of HbS and at increasing oxygen-carrying capacity.
The SCD has variable and complex clinical manifestations. Individuals with similar genetic mutations exhibit different degrees of severity of the disease. The influences of the environment and psychosocial factors cannot be ruled out as the underlying causes of these variations in clinical presentation. This complexity has posed a great challenge in the optimum care of patients with SCA. Thus, individualized management of the SCD crisis and complications should be the goal of treatment.
The health-seeking behavior of males and females has been shown to be different. Men are less likely to seek medical help when they need it, despite the fact that men are more likely to be financially buoyant than women and, as such, could pay for their clinic visits more readily than the women. This could be due to the pressure of work or due to “traditional masculine behavior.” It is, therefore, possible that gender differences could impact the severity/complications of SCA. This study, therefore, aims at determining the gender-related differences in the complications of SCA in patients with adult sickle cells in Enugu, southeast Nigeria.
| Patients and Methods|| |
This was a retrospective study of adult patients with SCA seen from February 2008 to February 2014 at the University of Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu, Nigeria. A total of 248 case notes of patients with SCD were retrieved from the medical records from the department of the hospital. This comprises 151 males and 97 females. The sociodemographic data as well as hematological parameters, number of complications, and frequency of sickle cell crises were collected, extracted using a Microsoft Excel Sheet, and analyzed. The mean frequency of crisis, mean levels of hematological parameters (white cell count, platelet count, and hemoglobin concentration), and the prevalence of complications were compared between the two genders. Ethical clearance was obtained from the institutional review board of UNTH, Ituku-Ozalla, Enugu.
The statistical package for social sciences (SPSS) computer software version 25.0 for Windows was used for analysis. Discrete variables were analyzed using chi-square and Fisher-exact tests, and associations were expressed using odds ratio and 95% confidence intervals. The mean values were compared between the male and female genders using the Student’s t-test. Statistical significance was set at P < 0.05.
| Results|| |
The median age was 25 years with an interquartile range (IQR) of 22–30 years. One hundred and fifty-one (151/248 [60.9%]) were males, whereas 97 (97/248 [39.1%]) were females. The demographic characteristics of the participants, including the median age, educational level, and occupation, were similar among the male and female gender [Table 1].
The overall mean white cell count, hemoglobin level, and platelet count of the participants were 12.1±6.7 x 109 /L, 7.7±1.7g/dl, and 339.4±163.1 x 109 /L, respectively. There were no significant differences between the mean white cell count, hemoglobin level, and platelet count of the male and female genders (P > 0.05). The details are shown in [Table 2].
|Table 2: Hematological parameters and frequency of sickle cell crises of the two genders|
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[Table 3] shows the frequency of vaso-occlusive painful crises in a year preceding the study. Although the mean frequency of crises in the males (15.00 ± 9.01) was higher than that of the females (9.8 ± 6.97), the observed difference was not statistically significant (P = 0.293). The details are shown in [Table 3].
|Table 3: Frequency of crises among patients with SCA per year in the preceding year|
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[Table 4] shows the various complications of SCA based on gender. A total of 182 out of 248 (73.4%) cases reviewed had one form of complication or the other. Overall, sickle cell leg ulcer was the most common complication observed (50 [50/182, 27.5%]), followed by AVN (28 [28/182, 15.4%]). One hundred and sixteen (116/151, 76.8%) males had one or more complications, whereas 59 (59/97, 60.8%) females had one or more complications. The observed difference was statistically significant (OR = 2.13; 95% CI = 1.2–3.7; P = 0.007). With regard to gender differences, leg ulcer and osteomyelitis were significantly higher in males than in females (P < 0.05). Other complications, including AVN, pulmonary hypertension, nephropathy, stroke, cholelithiasis, and septic arthritis, did not differ between the two genders (P > 0.05). The details are shown in [Table 4].
|Table 4: Some complications of patients with SCA in the study population|
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| Discussion|| |
This study has demonstrated that the male gender is twice more likely to develop sickle cell complications than the female gender. However, there was no statistically significant difference in the frequency of painful crisis between the two genders. The clinical implication of this observation is that male patients with SCA are more likely to suffer morbidities than their female counterparts. Awareness of this interesting observation will guide physicians during the evaluation and management of patients with SCA.
There are long-term complications of SCA, such as chronic anemia, increased susceptibility to infections, chronic leg ulcer, osteomyelitis, priapism, AVN, pulmonary hypertension, nephropathy, stroke, cholelithiasis, and septic arthritis. This study observed that leg ulcer and osteomyelitis were significantly higher in males than in females, whereas others did not show any significant differences. This finding is similar to that of Minniti et al., who also found a higher incidence of leg ulcers in males.
Although SCA, an autosomal recessive disorder, has no predilection for either sex regarding its inheritance, this study suggests that males are more vulnerable to complications than females. This finding is in keeping with the findings from previous works.,, The higher prevalence of SCD complications seen in males could be due to the poor health-seeking behavior of the male gender. They sometimes refrain from coming to hospital at the early stages of the illness but present when they are incapacitated—a behavior that, even though seen in both sexes, is more prevalent among males. Another important factor could be the higher exposure to stress and trauma from work and physical activities that the male gender is prone to. Many of them are employed in various occupations to enable them to provide for their families.
It was observed that 73.4% (182/248) of the cases had either one or more complications of SCA, with the most common being SLU (27.3%), followed by AVN (15.4%). Domingos et al. also found a higher prevalence of SLU compared with AVN in their work. However, some studies are at variance with the results of this study. They reported a higher occurrence of AVN than SLU., The difference may have been due to the retrospective nature of this study, which depended solely on the number of folders retrieved. Further, we also found that the male gender had a two-fold chance of developing SLU than the female gender. This finding is supported by previous studies., The SLUs are often recurrent and run an indolent course necessitating frequent hospital visits by the patient. The exact pathogenesis of the SLU is largely unknown, and they usually form at the medial and lateral malleoli. Many patients often have bilateral leg ulceration precipitated by trauma to the affected area.
Hormonal differences between the male and female sexes has been put forward as the possible reason for the increased prevalence of morbidity in the males. Estrogen has been shown to decrease nitic oxide degradation as well as to enhance its production.,[24 Nitric oxide has been documented to be involved in the transcriptional control of fetal hemoglobin (HbF). Hemoglobin F levels are higher in females than in males],[ and the severity of SCA is known to be higher in patients who have lower levels of HbF. Further, low levels of nitric oxide are associated with increased morbidity in patients with SCA.
Increased susceptibility to infections is seen in patients with SCD., In this study, a significant difference was noted between the number of males and females with osteomyelitis (P = 0.03). More females were noted to have chronic osteomyelitis than males. This is at variance with a previous study where the male gender had a higher prevalence of osteomyelitis. Patients with SCA are prone to infections because of functional hyposplenism and a defective alternative complement pathway. There has not been any confirmed reason for sex predilection to osteomyelitis or other infections in adults.
Priapism, which is a painful, purposeless, and persistent erection of the penis, was noted to be 23.2% (27/116). This value is lower than the 35% observed in a study done by Adeyoju et al. Also, in his review article in 2015, Adewoyin observed a prevalence rate ranging from 2% to 35%. The observed differences may be due to the differences in the data collection method used. Some studies used primary data, whereas others used secondary data following a retrospective study as in the present study.
Limitations of the study
This was a retrospective study using the case records of patients who presented at the Sickle cell clinic. The number of clinic visits was not taken into consideration, and the haplotypes of these patients were also not known despite the fact that they are possible confounders in this study. Again, the data for this work were from a single center and thus these limit the generalization of the results and findings. A future multicenter study with a large sample size will help to confirm the observed gender differences in the complications of SCA.
| Conclusion|| |
The male gender is at a higher risk of complications of SCA. They have a two-fold risk of developing leg ulceration when compared with the females. Public health awareness and regular clinic visits are, thus, encouraged to help prevent the occurrence or worsening of these complications.
This is a retrospective study. The institutional review board of the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu reviewed and gave an ethical clearance certificate.
Availability of data and material
The author is willing and ready to make data and material available whenever necessary.
Ugwu AO: Conception/design of article, data collection, data analysis, original draft preparation, and article writing/editing.
Financial support and sponsorship
This research was entirely self-funded.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]