Monika R. Asnani

Excess Risk of Maternal Death from Sickle Cell Disease in Jamaica: 1998–2007

Background Decreases in direct maternal deaths in Jamaica have been negated by growing indirect deaths. With sickle cell disease (SCD) a consistent underlying cause, we describe the epidemiology of maternal deaths in this population. Methods Demographic, service delivery and cause specific mortality rates were compared among women with (n = 42) and without SCD (n = 376), and between SCD women who died in 1998–2002 and 2003–7. Results Women with SCD had fewer viable pregnancies (p: 0.02) despite greater access to high risk antenatal care (p: 0.001), and more often died in an intensive care unit (p: 0.002). In the most recent period (2003–7) SCD women achieved more pregnancies (median 2 vs. 3; p: 0.009), made more antenatal visits (mean 3.3 vs. 7.3; p: 0.01) and were more often admitted antenatally (p:<0.0001). The maternal mortality ratio for SCD decedents was 7–11 times higher than the general population, with 41% of deaths attributable to their disorder. Cause specific mortality was higher for cardiovascular complications, gestational hypertension and haemorrhage. Respiratory failure was the leading immediate cause of death. Conclusions Women with SCD experience a significant excess risk of dying in pregnancy and childbirth [MMR: (SCD) 719/100,000, (non SCD) 78/100,000]. MDG5 cannot be realised without improving care for women with SCD. Tertiary services (e.g. ventilator support) are needed at regional centres to improve outcomes in this and other high risk populations. Universal SCD screening in pregnancy in populations of African and Mediterranean descent is needed as are guidelines for managing SCD pregnancies and educating families with SCD.

Higher Rates of Hemolysis Are Not Associated with Albuminuria in Jamaicans with Sickle Cell Disease

Background Albuminuria is a marker of glomerular damage in Sickle Cell Disease (SCD). In this study, we sought to determine the possible predictors of albuminuria in the two more prevalent genotypes of SCD among the Jamaica Sickle Cell Cohort Study participants. Methods An age-matched cohort of 122 patients with HbSS or HbSC genotypes had measurements of their morning urine albumin concentration, blood pressure, body mass index, haematology and certain biochemistry parameters done. Associations of albuminuria with possible predictors including hematological parameters, reticulocyte counts, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels were examined using multiple regression models. Results A total of 122 participants were recruited (mean age 28.6 years ±2.5 years; 85 HbSS, 37 HbSC). 25.9% with HbSS and 10.8% with HbSC disease had microalbuminuria (urine albumin/creatinine ratio  =  30–300 mg/g of creatinine) whereas 16.5% of HbSS and 2.7% of HbSC disease had macroalbuminuria (urine albumin/creatinine ratio>300 mg/g of creatinine). Mean arterial pressure, hemoglobin levels, serum creatinine, reticulocyte counts and white blood cell counts were statistically significant predictors of albuminuria in HbSS, whereas white blood cell counts and serum creatinine predicted albuminuria in HbSC disease. Both markers of chronic hemolysis, i.e. AST and LDH levels, showed no associations with albuminuria in either genotype. Conclusions Renal disease, as evidenced by excretion of increased amounts of albumin in urine due to a glomerulopathy, is a common end-organ complication in SCD. It is shown to be more severe in those with HbSS disease than in HbSC disease. Rising blood pressure, lower hemoglobin levels and higher white blood cell counts are hints to the clinician of impending renal disease, whereas higher rates of hemolysis do not appear to play a role in this complication of SCD.

Knowledge and health beliefs of Jamaican adolescents with sickle cell disease.

The adolescent stage of life is generally perceived to be a challenging period, which may be magnified when a chronic illness such as sickle cell disease (SCD) is present. In this study, we sought to determine the knowledge and health beliefs of Jamaican adolescents with SCD as these factors may impact their self‐management skills.

Determining Glomerular Filtration Rate in Homozygous Sickle Cell Disease: Utility of Serum Creatinine Based Estimating Equations

Background Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD. Methods 98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using 99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination. Results The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m2 BSA, with a range of 6.4–159.0 mls/min/1.73 m2. The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation. Conclusion Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m2 has been developed from our dataset and validated within a simulated dataset.

“You Just Have to Live With It” Coping With Sickle Cell Disease in Jamaica

Research has shown that living with sickle cell disease (SCD) can be a considerable challenge. Unfortunately, although it is Jamaica’s most common genetic disorder, to date, no qualitative research has been conducted on Jamaicans’ experiences of SCD. We conducted thematic analysis on transcripts of in-depth semistructured interviews with 30 patients and found two interlinked themes bound up in life with SCD: loss and control. Faced with important losses, respondents used cognitive and behavioral coping strategies to reestablish control over their response to SCD, others’ responses to SCD, and SCD’s physical manifestations. Although the adaptive nature of some of these strategies is debatable, many facilitate management of the illness. Health care practitioners should encourage positive coping strategies and have nonjudgmental discussions with patients about (potentially) negative ones. They should also share information with nonspecialist doctors and nurses to reduce stigmatization around the illness. More exploration of this underresearched topic is needed.

Locus of control, depression and quality of life among persons with sickle cell disease in Jamaica

This study explored how locus of control (LOC), depression and quality of life (QOL) interplay in patients with sickle cell disease. One hundred and forty-three sickle cell clinic patients with consecutive clinic consultations completed the Multidimensional Health Locus of Control and Short Factor 36 (SF-36) scales as well as the Beck Depression Inventory. Participants in this study had higher scores on the “chance”, “other people” and “internal” domains of LOC than persons with a number of other chronic illnesses in a previous study. Hierarchical regression analyses showed that high scores on the “internal” domain of LOC were associated with better QOL and fewer symptoms of depression. Depressive symptoms were greater in persons with high scores on the “other people” LOC domain and in younger persons. These findings would suggest that it is possible that interventions which enhance internal LOC and discourage “other people” orientations might improve QOL and ameliorate depression among persons with sickle cell disease.

Cystatin C: a useful marker of glomerulopathy in sickle cell disease?

As renal dysfunction is a leading cause of morbidity in sickle cell disease it is important that clinicians have accurate means of assessing its risk and severity. Cystatin C (Cys-C) is being recognized as a useful marker of renal function in other populations and this study aims to determine its utility in adults with sickle cell anemia (SCA). 98 persons with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had hematological and biochemical, including Cys-C, measurements; and glomerular filtration rate (GFR) measured using a (99m)Tc-DTPA nuclear renal scan. The measured GFR was 94.9±27.4mL/min/1.73m(2), and mean Cys-C level was 0.80±0.78mg/L. Cys-C was significantly correlated with measured GFR (r=-0.61), hemoglobin (r=-0.32), serum creatinine (r=0.91), urine ACR (r=0.79), and systolic blood pressure (r=0.38). The Cys-C based CKD-EPI showed the greatest agreement than the other commonly used Cys-C based as well as the serum creatinine based MDRD and CKD-EPI equations. Cys-C also showed a strong association with GFR in a significant regression model. In conclusion, Cys-C has shown strong associations with GFR and albuminuria among patients with SCA and so may be a useful screening tool in this patient population.

Predictors of renal function progression in adults with homozygous sickle cell disease

Longitudinal studies of renal function may improve understanding of the pathophysiological mechanisms underlying sickle cell disease (SCD) nephropathy and may identify possible biological and clinical markers of renal function determined over time. Data from the Jamaica Sickle Cell Cohort Study (JSCCS) were extracted and the glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiological and the SCD specific JSCCS‐GFR equations from all adulthood serum creatinine measurements in homozygous SS patients. The other dataset consisted of measured GFR at two times about 13 years apart. Linear mixed model (LMM) regression analyses were conducted to determine predictors of GFR and serum creatinine over time. 191 individuals with SS disease had 867 GFR estimates available. Serum creatinine significantly increased from baseline whereas estimated GFR showed a significant decline. Serum creatinine showed positive association with increasing age, male gender, body mass index and sodium levels. Haemoglobin was a significant negative predictor of estimated GFR in age‐ and gender‐adjusted models. A total of 24 females and 17 males had repeat measurements of their GFR. The mean annual decline in GFR was −3·2 ± 2·83 ml/min/1·73 m2. Haemoglobin was a significant positive predictor whereas serum creatinine, systolic blood pressure and urinary albumin: creatinine ratio were negative predictors of GFR.

Renal function in adult Jamaicans with homozygous sickle cell disease

Abstract Objectives As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD. Methods Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual. Results Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m2. Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis. Conclusion We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population.

Increased rates of body dissatisfaction, depressive symptoms, and suicide attempts in Jamaican teens with sickle cell disease

This study aims to examine the association of body image and weight perceptions with risk of depression and suicidal attempts in Jamaican adolescents with sickle cell disease (SCD).