Impact of Binet Staging versus Tumour Bulk on Treatment Outcome in Chronic Lymphocytic Leukaemia.

BACKGROUND: Most of the predictive tools put up to prognosticate treatment outcomes in patients with chronic lymphocytic leukaemia (CLL) are not easily available and affordable in our resource-constrained environment. AIM: The aim of this study was to evaluate the impact of staging and some tumour bulk on treatment outcomes of persons with CLL, Enugu, Nigeria. PATIENTS AND METHODS: This is a 10-year review of the CLL data from the haemato-oncology unit of a Nigerian tertiary hospital to evaluate the impact of staging and tumour bulk indicators. Data were retrieved from the case notes of 102 patients with CLL receiving care at the facility. Data of interest include basic demographic variables, clinical features including spleen size and disease staging and blood counts. Statistical analysis was done using SPSS version 22. RESULTS: The median absolute lymphocyte count (ALC) was 108.05 (confidence interval [CI] = 50.8-201.3, interquartile range [IQR] = 124.4) ×109/L, and duration of survival for the study cohort was 5.5 (CI = 3.5-31.9, IQR = 27) months. Majority (69, 79.3%) were in Stage C. The Binet stage showed a significant association with the ALC (r = 0.338; P = 0.002) but not with spleen size (r = 0.198; P = 0.056). The duration of survival only showed a significant inverse relationship with the ALC (r = 0.35, P = 0.006) but with neither the Binet stage (r = 0.103, P = 0.431) nor spleen size (r = 0.184, P = 0.116). CONCLUSION: In CLL patients, ALC at presentation correlates with the duration of survival. We recommend that the ALC at presentation be used as a prognostic marker in our clime.

Prevalence of venous thromboembolism and its associations in a large racially homogenous population of sickle cell disease patients.

To determine the prevalence of venous thromboembolism (VTE) among adult sickle cell disease (SCD) patients in Nigeria. METHODS: This was a multicentre retrospective study in which the medical records of adult SCD patients were reviewed. Information on demographics, steady-state haemogram, clinical phenotypes, duration of follow-up, history of VTE including risk factors and management was collected. RESULTS: Of the 509 SCD patients with a median (IQR) duration of follow-up of 2 years, 10 (2.0%) had VTE (9 DVT and 1 PE). Their median (IQR) age was 27 (22.8-30.3) years. Identifiable risk factors for VTE included positive family history (2, 20%) surgery, splenectomy, paraplegia and cancer (1, 10% each). No risk factor was identifiable in four persons. VTE had no significant association with age and gender. VTE was significantly associated with the following events: acute chest syndrome [p = .002, odds ratio (OR) 8, 95% CI 2.2-28.9], osteonecrosis [p = .012, OR 5.24, 95% CI, 1.45-18.91] and vaso-occlusive crisis [p = .035]. Also significantly associated with VTE were pulmonary hypertension [p = .001, OR 23.3, 95%CI 5.18-105.06] and stroke [p = .032, OR 9.35, 95%CI 0.87-53.25]. CONCLUSION: The prevalence of VTE among SCD patients in Nigeria is low. It is significantly associated with vaso-occlusive crisis, pulmonary hypertension and stroke.

Variations and characteristics of the various clinical phenotypes in a cohort of Nigerian sickle cell patients.

BACKGROUND: Sickle cell anaemia affects about 4 million people across the globe, making it an inherited disorder of public health importance. Red cell lysis consequent upon haemoglobin crystallization and repeated sickling leads to anaemia and a baseline strain on haemopoiesis. Vaso-occlusion and haemolysis underlies majority of the chronic complications of sickle cell. We evaluated the clinical and laboratory features observed across the various clinical phenotypes in adult sickle cell disease patients. METHODS: Steady state data collected prospectively in a cohort of adult sickle cell disease patients as out-patients between July 2010 and July 2020. The information included epidemiological, clinical and laboratory data. RESULTS: About 270 patients were captured in this study (165 males and 105 females). Their ages ranged from 16 to 55 years, with a median age of 25 years. Sixty-eight had leg ulcers, 43 of the males had priapism (erectile dysfunction in 8), 42 had AVN, 31 had nephropathy, 23 had osteomyelitis, 15 had osteoarthritis, 12 had cholelithiasis, 10 had stroke or other neurological impairment, 5 had pulmonary hypertension, while 23 had other complications. Frequency of crisis ranged from 0 to >10/year median of 2. Of the 219 recorded, 148 of the patients had been transfused in the past, while 71 had not. CONCLUSION: The prevalence of SLU, AVN, priapism, nephropathy and the other complications of SCD show some variations from other studies. This variation in the clinical parameters across different clinical phenotypes indicates an interplay between age, genetic and environmental factors.

Barriers to Therapeutic Use of Hydroxyurea for Sickle Cell Disease in Nigeria: A Cross-Sectional Survey.

Background: Sickle cell disease, the inherited blood disorder characterized by anemia, severe pain and other vaso-occlusive complications, acute chest syndrome, disproportionate hospitalization, and early mortality, has significant financial, social, and psychosocial impacts and drains individuals, families, and health systems globally. Hydroxyurea could improve the health of the 300,000 individuals born each year with sickle cell disease in sub-Saharan Africa; however, challenges to adoption and adherence persist. This study assessed the barriers to therapeutic use of hydroxyurea for sickle cell disease within the Nigerian healthcare system, specifically from the level of the patient, provider, and health system. Methods: We used purposive sampling to recruit participants from 13 regions in Nigeria. A cross-sectional survey was administered to physicians (n = 70), nurses or counselors (n = 17), and patients or their caregivers (n = 33) at 13 health centers. Findings were mapped onto the appropriate Consolidated Framework for Implementation Research (CFIR) domains. Results: This study was able to identify factors that mapped onto the inner setting, outer setting, and characteristics of individuals domains of CFIR. The majority of physicians (74.3%) prescribe hydroxyurea, and half stated hydroxyurea is the standard of care. Among clinicians, barriers included limited knowledge of the drug, as well as low self-efficacy to prescribe among physicians and to counsel among nurses; perceived side effects; perceived patient preference for traditional medicine; cost for patient and expense of accompanying laboratory monitoring; and limited availability of the drug and equipment for laboratory monitoring. Among patients and caregivers, barriers included lack of knowledge; perceived side effects; cost; religious beliefs of disease causation; and lack of pediatric formulation. Conclusions: Findings suggest that patient, provider, and health systems-level interventions are needed to improve hydroxyurea uptake among providers and adherence among patients with sickle cell disease in Nigeria. Interventions such as patient education, provider training, and policy change could address the disproportionate burden of sickle cell disease in sub-Saharan Africa and thus improve health equity.

Hyperhaemolytic Syndrome in Sickle Cell Disease: Clearing the Cobwebs.

Sickle cell disease (SCD) presents with a dynamic background of haemolysis and deepening anaemia. This increases the demand for transfusion if any additional strain on haemopoiesis is encountered due to any other physiological or pathological causes. Patients with cerebrovascular accidents are placed on chronic blood transfusion; those with acute sequestration and acute chest syndrome are likewise managed with blood transfusion. These patients are prone to develop complications of blood transfusion including alloimmunization and hyperhaemolytic syndrome (HHS). This term is used to describe haemolysis of both transfused and "own" red cells occurring during or post-transfusion in sickle cell patients. Hyperhaemolysis results in worsening post-transfusion haemoglobin due attendant haemolysis of both transfused and autologous red cells. The mechanism underlying this rare and usually fatal complication of SCD has been thought to be secondary to changes in the red cell membrane with associated immunological reactions against exposed cell membrane phospholipids. The predisposition to HHS in sickle cell is also varied and the search for a prediction pattern or value has been evasive. This review discusses the pathogenesis, risk factors and treatment of HHS, elaborating on what is known of this rare condition.

Parental Perception of Childhood Anaemia and Efficiency of Instrument Assisted Pallor Detection among Mothers in Southeast Nigeria: A Field Validation Study.

BACKGROUND: Control of anemia can be achieved with early detection of pallor by parents at home. However, most parents lack the capacity to recognize pallor; thus most cases of anaemia are detected during hospital visit due to other symptoms. This study aimed to evaluate parental ability to detect pallor when aided with the anaemia screening tool. METHODS: In the study information on the symptoms of illness and parental knowledge on anaemia. Their ability to detect anaemia aided with the Home-Base anaemia-screen tool (HB-Anae) was compared to the healthcare providers' assessment of pallor. The haemoglobin estimation with the Hb-301 haemoglobinometer was used as the gold standard. RESULTS: None of the children in their previous illnesses had paleness as a complaint. Few (20.8%) parents knew what anaemia meant. Only 18.3% knew sites on the body where pallor can be detected. Many (55.1%; 304/552) surveyed children were anaemic (Hb<11g/dl) based on HB 301. Majority (88.8%; 270/304) of the parents aided with the HB-Anae were able to detect pallor on the children who were anaemic compared to 95.1% (289/304) detected by healthcare workers unaided, and the difference was not statistically significant (p=0.25). CONCLUSION: There was poor knowledge on anaemia among parents. The ability of parents to detect anaemia could be improved with the simple HB-Anae screen tool.

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria.

Background: Chronic lymphocytic leukaemia is a relatively common haematological malignancy affecting older adults, accounting for about 20% of haematological malignancies in Nigeria. Diagnosis of this disease depends on the demonstration of clonal lymphocytosis > 5 × 109/L with a characteristic immunophenotypic pattern amidst other clinical and laboratory features. Objectives: To determine the predominant clinical and laboratory features of CLL at presentation and their relationship with patient survival. This study also aims at examining the relationship between treatment protocol and outcome. Methods: This is a retrospective study with 8 years data (2010-2018) collected from four different centers. Data was analyzed using SPSS 20.0. Results: There were a total of 97 cases, with a male: female ratio of 1.1:1. The median age at presentation was 59 years. Approximately 55% of the patients presented at Binet stage C, with splenomegaly in 93.2% and 78% were anaemic. The mean white cell count was 137.9 ± 14.7 × 109/L, with a median absolute lymphocyte count of 86 × 109/L. The commonest treatment regimen was chlorambucil and prednisolone and males had a superior response. The number of chemotherapy cycles, serum alkaline phosphatase and aspartate transaminase correlated positively with duration of survival. Mortality rate over the five year period was 14.3%. Conclusion: CLL was found to present in younger patients when compared to previous studies with a median age of 57 years at diagnosis. Our study showed a slight female preponderance and better response to therapy in males. Majority of the patients presented in Binet stage C and were treated with chlorambucil-based drug combinations compared to more current treatment with Fludarabine-based combinations. A high serum alanine transaminase and alkaline phosphatase was found to positively correlate with survival amongst this patient population.

Evaluation of the Performance of Haemoglobin Colour Scale and Comparison with HemoCue Haemoglobin Assay in Diagnosing Childhood Anaemia: A Field Validation Study.

BACKGROUND: Anaemia in children has high mortality. We present the results of assessment of the accuracy of Haemoglobin Colour Scale in identifying anaemia compared with HemoCue assay. METHODS: The presence of anaemia in 524 children from four communities was screened using the Haemoglobin Colour Scale (HCS) and HemoCue assay. Independent healthcare providers that estimated the haemoglobin level using Hb-301 haemoglobinometer were different from those that read the colour scale. The sensitivity, specificity, positive predictive value, and negative predictive value were estimated. RESULTS: Of the 524 children surveyed, 44.5% (233/524), 50% (262/524), and 32.2% (168/524) were found to be anaemic using the HemoCue, HCS (p= 0.25), and clinical pallor (p=0.03) respectively. Using the HemoCue as standard, the sensitivity of the HCS and clinical pallor was 89.1% and 72.1%, respectively, and specificity 90.2% and 84.6%, respectively. 74.7 % of the colour scale result was within the 1.0g/dl of the HemoCue reading and 23 % was within 2.0g/dl. CONCLUSION: The HCS can improve the ability to detect anaemia especially where the use of the HemoCue is not feasible as in the resource poor countries. However, every case of anaemia requires further investigation to determine the underlying causes.

Correlates of neutrophil/lymphocyte, platelet/lymphocyte, and platelet/neutrophil ratios of neonates of women with hypertensive disease of pregnancy with neonatal birth outcomes.

BACKGROUND: Studies have indicated neutrophil/lymphocyte ratio (NLR), Platelet/Lymphocyte ratio (PLR), and platelet/neutrophils ratio (PNR) to be inflammatory markers. The correlation of these values in infants of hypertensive mothers has not been investigated. AIM: To investigate the relationship between NLR, PLR, and PNR of neonates of women with hypertensive disease of pregnancy and neonatal APGAR scores and birth weight. METHODOLOGY: Cord blood samples of 200 neonates collected and the blood counts and ratios obtained. RESULTS: NLR in the babies of the hypertensive mothers was 0.865 and 1.42 in the control group (p = 0.0001). PLR was 34.7 in the neonates of the hypertensive mothers and 62.4 in the control group (p = 0.0001). PNR did not differ significantly between the two groups,p = 0.418. Degree of hypertension had a direct relationship with NLR; SBP had a p value of 0.001 while the DBP had p = 0.002. The PLR had an inverse relationship with the degree of hypertension; SBP p value of 0.0001, while DBP was p = 0.0001. No significant association was observed between the ratios and neonatal birth weight (p ≥ 0.05); however, PNR and PLR were found to be significantly associated with the 1st (p = 0.045 and 0.030) and 5th (0.049 and 0.037) minute APGAR scores in the newborns. CONCLUSION: PLR and NLR in neonates of hypertensive mothers are found to be markedly lower than those of controls, the degree of which is affected by the severity of hypertension. Also, lower PLR is associated with lower APGAR scores. Therefore, severity of high blood pressure and lower PLR may be determinants of poor birth outcome.

Clinical and Laboratory Predictors of Frequency of Painful Crises among Sickle Cell Anaemia Patients in Nigeria.

INTRODUCTION: The severity of Sickle Cell Anaemia (SCA) in terms of frequency of painful Vaso-Occlusive Crises (VOC) may be affected by clinical and haematological parameters amongst others. Elucidation of these factors in a given disease prevalent environment is necessary for prompt and effective management of patients with frequent painful VOC. AIM: This study aimed at determining the clinical and laboratory predictors of frequency of painful VOC among SCA patients in Enugu, Southeastern Nigeria. MATERIALS AND METHODS: It was a cross-sectional study of 100 consecutive SCA patients receiving care at the University of Nigeria Teaching Hospital, Enugu, Nigeria between May 2012 and February 2014. The eligible patients were categorized into two groups namely; Group A and Group B. Group A/study group (severe disease) comprised SCA patients who had experienced three or more painful crises (≥3 crises) in the last one year preceding the study but, currently in steady state, while Group B/control group (mild-moderate disease), comprised SCA patients matched for age, sex, highest educational status, and occupation but who have had no painful crisis or had only one or two painful crises (0-2 crises) in the last one year preceding the study and currently in steady state. RESULTS: The overall mean age of the patients was 18.4±12.2 (range=2-52) years. The mean values of the haematological parameters including haemoglobin concentration, white cell count, platelet count, and neutrophil count were significantly higher in those with severe crises than mild-moderate crises (p<0.05). Sickle cell related complications including Avascular Necrosis (AVN) and leg ulcers were significantly higher in the study group than the control group (p<0.05). CONCLUSION: There was significant association between the frequency of crises and haemogblobin level, platelet and neutrophil counts and some clinical parameters: AVN, nephropathy and stroke. Future preventive interventions for reduction in frequency of crisis amongst patients with SCA could be targeted at controlling the blood levels of the identified haematological parameters.

Clinical Anaemia Detection in Children of Varied Skin Complexion: A Community-based Study in Southeast, Nigeria.

BACKGROUND: Clinicians rely on clinical detection of pallor to diagnose anaemia. This makes it important to evaluate the effect of different skin complexions on the accuracy of the pallor in diagnosing anaemia in children. METHODS: Clinicians conducted blind-independent physical examination, and their reports were compared with HemoCue 301 haemoglobin estimated with. The sensitivity and specificity were calculated. RESULTS: A total of 573 children were reviewed by 27 healthcare workers. The prevalence of anaemia was high. The highest prevalence was among children between the age of 4 and 12 months (urban 63.4% and rural 69.2%). Anaemia was detected better among dark-skinned children. Conjunctivae and palm pallor had the highest sensitivity (78.6% and 69.2%, respectively). DISCUSSION: Clinical pallor is a good screening assessment for anaemia but not diagnostic. Its sensitivity and specificity vary among different sites and skin complexions. Thus combining findings at any of the sites can improve detection of anaemia in children.

Anaemia of Chronic Disease: An In-Depth Review.

Anaemia is the most common haematological disorder affecting humanity and is usually observed in chronic disease states such as non-specific anaemia, which may cause diagnostic difficulties. In chronically ill patients with anaemia, this has a negative impact on quality of life as well as survival. This paper aims at reviewing the pathogenesis of this form of anaemia with a view to suggesting future targets for therapeutic intervention. The ability to diagnose this disorder depends on the ability of the physician to correlate the possible clinical pathways of the underlying disease with the patients' ferrokinetic state. It is important to rule out iron deficiency and other causes of anaemia as misdiagnosis will in most cases lead to refractoriness to standard therapy. The cytokines and acute-phase proteins play important roles in the pathogenesis of anaemia of chronic disease. Alterations in the metabolism of iron via the molecule hepcidin and ferritin are largely responsible for the consequent anaemia. Concomitant iron deficiency might be present and could affect the diagnosis and therapeutic protocol. Treatment options involve the use of erythropoiesis-stimulating agents, blood transfusion, and iron supplementation, in addition to treating the underlying disease.

Priapism in homozygous sickle cell patients: important clinical and laboratory associations.

OBJECTIVE: To evaluate the relationship between the occurrence of priapism and important steady-state clinical and laboratory parameters in homozygous sickle cell disease (SCD). SUBJECTS AND METHODS: Steady-state clinical and laboratory data were obtained from the medical records of 126 male patients seen in the clinic over a 7-year period. Estimated prevalence rates, correlation coefficients and independent t tests were calculated to assess the relationship between priapism and several important clinical and laboratory indices. Patient data on age, haemoglobin concentrations, the frequency of crises per annum, leucocyte counts, platelet counts, serum bilirubin and aspartate transaminase were evaluated. RESULTS: The prevalence of priapism was determined to be 21.4%, and 22.2% of those affected had erectile dysfunction. There was a significant positive correlation between priapism and older age (p = 0.049) and lower leucocyte counts (p = 0.008). There was no significant relationship with other clinical or laboratory indices. CONCLUSION: About 1 in 4 of all homozygous older SCD patients had priapism, and an approximately similar ratio developed erectile dysfunction; they also had lower steady-state leucocyte counts. Other clinical and laboratory indicators of disease severity in SCD did not positively correlate with the occurrence of priapism, and this may imply an alternative pathogenetic mechanism.

Evaluation of clinical and laboratory correlates of sickle leg ulcers.

The exact mechanism for the occurrence of sickle leg ulcers (SLUs) has not been fully explained, although, popular opinion supports a multifactorial etio-pathogenetic process. Leg ulceration in sickle cell is a chronic and debilitating condition which is difficult to treat and may worsen the psychosocial impact of this illness. This study aims to evaluate the laboratory and clinical correlates of SLUs. One hundred sixty-seven patients who had been diagnosed with sickle cell anemia (homozygous S) had their steady-state hemoglobin concentration (Hb), hematocrit, white cell count, platelet count, serum bilirubin, and aspartate transaminase (AST) as well as frequency of crisis per annum evaluated with respect to their relationship to the occurrence of leg ulcers. They were aged 6-53 years (mean age 24.3 years), and prevalence of leg ulcer was found to be 2.75 per 1000 (2.54 per 1000 in females and 2.83 per 1000 in males). The independent sample t-test showed a significant difference in the serum AST levels in those with SLU (p = 0.029), though a positive correlation did not exist. Other predictors of disease severity found to have positive relationship with each other were the AST and total serum bilirubin 0.207 (p = 0.012); Hb and age 0.130 (p = 0.035); Hb and white cell count -0.159 (p = 0.010), white cell count and age -0.113 (p = 0.018). SLUs do not occur in patients with severe disease in sickle cell. The clinical and laboratory indicators of severe sickle cell disease do not correlate positively with the occurrence of SLU. Serum AST may have a relationship with leg ulceration in these patients. Environmental factors most likely play a major part in the etiopathogenesis of leg ulcer and this may require further studies in different sociocultural settings.