Variation in Pain and Clinical Indices among Patients with Sickle Cell Disease in Ghana

Research Article

J Blood Disord. 2016; 3(1): 1037.

Variation in Pain and Clinical Indices among Patients with Sickle Cell Disease in Ghana

Ababio GK¹, Acquaye J², Ekem I², Aleksenko L³ and Quaye IK4*

¹Department of Medical Biochemistry, University of Ghana, Ghana

²Department of Hematology, University of Ghana, Ghana

³Department of Pathology, University of Namibia, Namibia

4Department of Biochemistry and Microbiology, University of Namibia, Namibia

*Corresponding author: Quaye IK, Department of Biochemistry and Microbiology, University of Namibia, PBAG, 13301, Windhoek, Namibia

Received: March 01, 2016; Accepted: May 09, 2016; Published: May 11, 2016


Background: Patients with Sickle Cell Disease (SCD) have acute pain episodes that vary between patients. We examined whether differences exist in socio-demographic profiles, blood indices and pain attributed fear of movement in SCD.

Methods: The study included 287 patients with SCD attending the outpatient SCD clinic of the Korle-Bu Teaching Hospital, Accra, Ghana. We documented socio-demographic information, clinical history and pain location at enrolment. Blood sample was also taken for hematological analysis. We used the numeric descriptor, verbal and visual analog scales to determine the site and spectrum of pain intensity, and the Tampa Scale of Kinesiophobia (TSK) to assess pain attributed fear of movement.

Results: Patients with SCD were more literate than their healthy controls (χ2, p=0.0001). By genotypes, patients with HbSS were younger in age and had lower BMI, p=0.0001, 95% CI: -10.1 – 3.6; and p=0.01, 95% CI -4.13- 0.46. Pain was the most common clinical manifestation in both HbSS and HbSC (17.7% and 25.7% respectively) disease, presenting mainly as musculoskeletal pain (81.3%). Patients with HbSS were anemic, with indicators of hemolytic episodes and elevated WBCs and Platelets (p=0.0001.), depicting an inflammatory state. The disease profile of patients with HbSS was generally severer (OR= 1.695, 95% CI: 1.035-2.776 p=0.036) with a higher score of pain attributed fear of movement (p=0.0001, 95% CI: 2.2 – 6.0).

Conclusion: Pain is a significant index of disease in patients with SCD, particularly in those with HbSS genotype leading to fear of movement. Efforts at involving patients in coping strategies and pain mitigation in management are warranted.

Keywords: Pain and sickle cell disease; Sickle cell disease; Fear of movement; Ghana


SCD: Sickle Cell Disease; SCA: Sickle Cell Anemia; HbSS: Hemoglobin SS mutant; HbSC: Hemoglobin SC mutant, RBC: Red Blood Cell; MCV: Mean Cell Volume; MPV: Mean Platelet Volume; Hct: Hematocrit; Plt: Platelet; WBC: White Blood Cell; Hb: Hemoglobin; MCH: Mean Corpuscular Hemoglobin; LDH: Lactate Dehydrogenase; BMI: Body Mass Index; TSK: Tampa Scale of Kinesiophobia


Sickle Cell Disease (SCD) is a co-dominant genetic disorder [1,2] characterized by the HbS variant of β-globin gene [3]. The common forms of SCD are HbSS, HbSC, HbSD, HbSE and HbS β°/β Thalassemia [4], due respectively to missense mutations E6V (β6 GAG→GTG), E6K (β6 GAG→AAG), E26K (β26 GAG→AAG), E22V (β22 GAG→ GTG) and β°/+. The homozygous HbSS variant is referred to as Sickle Cell Anemia (SCA), which is one of the most commonly inherited genetic disorders, in the world [5]. In SCA, HbS polymerization under low oxygen tension leads to dehydration, rigidity and increased red cell density [6]. This phenotype increases vaso-occlusion risk in small blood vessels, impairs blood flow and leads to tissue necrosis so that in reperfusion, an inflammatory response is elicited inducing acute pain episodes [7,8]. Patients with SCA have the highest episodes of pain which is reported to increase in frequency from 6 months of birth and dominates the clinical presentation [9,10]. Most hospitalizations in SCD are due to pain crisis, largely acute episodic nociceptive pain [11-13]. In general the major clinical indices known to contribute to heightened pain are genotype (SCA verses HbSC) [14], hemolysis [15], decreased hematocrit or anemia [16] and decreased fetal hemoglobin (HbF) [17]. There is evidence that these factors do not necessarily translate into heightened pain. For example it is reported that chronic hyper-hemolysis is associated with fewer episodes of pain [18,19]. In addition, in a study of pain involving 3578 patients in the Cooperative Study of Sickle Cell Diseases (CSSCD), 5.2% had 3-10 painful episodes annually that required medical care, while 39% had no pain [19]. Clearly gaps exist in the knowledge of patient factors associated with pain, which requires more data collection from different populations. As mentioned previously, while genetic factors are important in disease phenotype, environmental factors, in particular sociodemographic factors are also major contributors. We reasoned that differences in socio-demographic factors between patients may contribute partially to the observed variation in pain manifestation, in addition to disease genotypes and hematological profiles. We also hypothesized that heightened pain episodes in SCD could lead to a morbid state with regards to fear of movement which may differ by genotypes (HbSS and HbSC). So we have characterized differences in demographic, hematological indices and pain attributed fear of movement in patients with SCD (HbSS and HbSC) in Ghana.

Materials and Methods

Study subjects

We enrolled 294 patients with sickle cell disease presenting to the SCD clinic of the Korle-Bu teaching Hospital Accra, Ghana, and 624 controls who qualified to donate blood at the national blood transfusion center, consecutively. The sample size was determined using the formula: N=Z2 (P) (1-P)/ (Error) 2, where Z= standard score for the confidence interval of 95% and equals 1.96. P is the sample proportion of the prevalence of an S allele which is 0.78 and for C allele 0.22 in the population studied. Assuming an error of 5% in this estimate, the sample size per group with an SS and SC genotypes are respectively 175 and 98. The enrolment followed ethical approval by the University of Ghana Medical School Ethical Committee and patients’ informed consent. Inclusion criteria depended on subjects having SCD and undergoing follow up visits at the Center for Clinical Genetics, Korle-Bu Teaching Hospital. Patients with sickle cell disease and with acquired hemolysis or known glucose-6-phosphate dehydrogenase deficiency (G-6-PD) were excluded. Non-sickle cell disease subjects declared medically fit to donate blood at the National Blood Donation Center, Korle-Bu Teaching Hospital, and Accra, served as controls.


At enrolment, demographic data (age, education) and clinical information (previous infection or disease) were obtained from each subject with a questionnaire either verbally and/or from their folders. Anthropometric measurements (weight (kg) and height (m)) for BMI were also taken.

Pain assessment

We defined pain as that occurring at the extremities, back, abdomen, chest and ribs, head and neck that lasted a minimum of 30 minutes and which could not be explained during a clinic visit except SCD. Pain intensity was assessed over the preceding seven days. We used the Numeric Rating Scale (NRS), Visual Analogue Scale (VAS) and Verbal Descriptors Scale (VDS) to designate the pain intensity, while the Tampa Scale of Kinesiophobia (TSK) was used to assess pain associated disability attributed to fear of movement and musculoskeletal pain. We defined musculoskeletal pain in our context as: back pain, head and neck pain, chest and ribs and general bodily pains. The NRS, VDS and VAS included a body diagram and mood cartoons to enable the patient indicate the exact location of the pain and feeling about the pain. Responses were categorized into four tiers according to the WHO analgesic ladder: without pain (0), mild pain (1-3), moderate pain (4-7) and intense/severe pain (8-10).

Blood collection and analysis

Four millimeters (4ml) blood was drawn from an antecubital vein by means of a plastic syringe and dispensed into EDTA (ethylenediamine tetra -acetic acid) tubes and immediately mixed gently over a roller. This was used to determine the Full Blood Count (Red Blood Cells, Mean Cell Volume, Hematocrit, Hemoglobin, Mean Platelet Volume, Platelet count and White Blood Cells). The Swelab TMAlfaLyse 1504125 (Stockholm, Sweden) analyzer was used for the Full Blood Count, after a control sample had been used to standardize the analyzer. Hb phenotyping was done by cellulose acetate electrophoresis.

Statistical analysis

Data were captured into an excel spreadsheet and analyzed with Graph Pad Prism and EPI Info. Differences between the means of the hematological indices were determined by student’s t-test. The association between the groups of patients with different types of SCD (HbSS and HbSC) and pain were assessed by Chi-square and Fisher’s exact tests with Odds ratio and 95% Confidence interval.


A total of 294 patients with sickle cell disease and 624 control subjects were enrolled into the study. Those lost to follow up were seven (7) patients and 36 control subjects to give a final patient population of 287 (186 HbSS, (77 males, 109 females) 101 HbSC (32 males, 69 females) and 588 control subjects (518 males, 70 females). Patients and control subjects lost to follow up declined later to participate in the study. Details of the demographic variables for all subjects are presented in Table 1. Subjects with HbSS genotype were the youngest and had the least BMI (mean ± SD; age: 25.1 ± 12.8; BMI: 19.9 ± 3.5 p=0.0001) in the group. Subjects with HbSC genotype were comparable in age to the controls although their BMI was also lower (age: 32.0 ± 13.7, 31.6 ± 8.6; p=.0001; BMI: 22.2 ± 5.1, 27.0 ± 3.5, respectively). Out of the 588 control subjects, 100 were randomly sampled for Hb phenotyping and were found to consist of HbAA (63), HbAS (28) and HbAC (9). The age and BMI of these control sub groups were similar. Patients with SCD were more likely to have attained at least a secondary education than the control subjects, HbSS vs controls, OR=6.2, 95% CI: 3.8-10.2 χ2, p=.0001; HbSC vs controls, OR=4.4, 95% CI: 2.4-8.2, p=0.0001.