Predictors of In-Hospital Mortality and Charges in Sickle Cell Disease: Results from the California Discharge Databases 1998–2005.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 432-432 ◽  
Author(s):  
John J. Strouse ◽  
Carlton Haywood ◽  
Sophie Lanzkron

Abstract Most studies of survival in sickle cell disease (SCD) include only patients followed at referral centers. We used the public set of the California Patient Discharge Databases (1998–2005) to compare in-hospital mortality and charges by patient characteristics. We included discharges with any diagnostic code for SCD (282.41–2, 282.60–69). We used the Charlson index (adapted for administrative data) to adjust for comorbid conditions. Hospital charges were adjusted to 1998 levels. Statistical methods included ANOVA, Wilcoxon rank-sum, and multivariate linear and logistic regression. We identified 57,887 admissions for SCD and 376 in-hospital deaths (0.65%) from 1998–2005. The mean age of death was 40 years (95% CI 38–42) for sickle cell anemia (HbSS) and 48.3 years (95% CI 44.1–52.5, p<.0005) for all other SCD. Median length of stay was 4 days (IQR 2–7 days) and charges were $10,027 (IQR 5547–18,302) for HbSS and 4 days (IQR 2–6 days) and $8045 (IQR 4375–16,253) for all other SCD (p<.0001). Women with SCD were older at the time of death (43.6 years) than men (41.4 years, p=.29) and age of death increased from 40.6 years in 1998–2000 to 44.2 in 2004–2005 (p=.17) but these differences were not significant. Mortality was increased with a Charlson Index of 1 or 2, older age, private insurance, a diagnosis of HbSS, and transfusion during the admission (Table 1). Women had a lower odds of death than men (OR 0.7, p<.05). Average annual charges for hospitalization in patients with SCD, adjusted to 1998 values, were $117,000,000 and decreased $1,960,000/year (−4.1%, p<.0001) for children and increased $1,150,000/year (1.4% p<0.05) for adults. Adjusted charges for all children were stable and increased 1.5% per year for adults. Charges per admission were $3167 higher for adults than children, $5608 higher per comorbid diagnosis, $6506 higher in transfused patients, and $3595 higher with a diagnosis of crisis (p<.0001 for all). Compared to MediCal, charges were $1186 higher for Medicare (p<.05), $2651 lower for other government insurance (p<.0001), and $3521 lower for self-pay (p<.05). Government (77%) and private insurance (21%) paid for most admissions. We identified a greatly increased risk of in-hospital morality with comorbid diagnoses and older age and moderately increased risk with private insurance, HbSS genotype, and transfusion during the admission. The increased risk with private insurance was surprising, as higher socioeconomic status is often associated with better health outcomes. This may reflect more stringent requirements for admission or financial barriers to outpatient and preventive services for SCD. Total charges decreased dramatically in children, possibly reflecting increased use of hydroxyurea for frequent pain and chronic transfusions for primary stroke prevention. Table 1: Odds Ratio for In-Hospital Death Based on Multivariate Logistic Regression Variable Odds Ratio (95% CI) P-Value NS indicates not significant Charlson Index=1 3.3 (2.4–4.6) <.0001 Charlson Index=2 12.9 (9.3–18) <.0001 Age (per year) 1.04 (1.03–1.05) <.0001 Private Insurance vs. MediCal 1.6 (1.2–2.2) <.0005 Medicare vs. MediCal 0.9 (0.7–1.3) NS Other SCD vs. HbSS 0.7 (0.5–0.9) <.0005 Transfusion 1.6 (1.2–2.0) <.0001

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 908-912 ◽  
Author(s):  
Harland Austin ◽  
Nigel S. Key ◽  
Jane M. Benson ◽  
Cathy Lally ◽  
Nicole F. Dowling ◽  
...  

Abstract People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1255-1255
Author(s):  
Abel Costa Neto ◽  
Flávia Leite Santos ◽  
Ingrid Helena Ribeiro ◽  
Valeria Brito Oliveira ◽  
Marcia Regina Dezan ◽  
...  

Abstract Introduction: Red blood cell (RBC) alloimmunization is an important transfusion complication which is very prevalent among patients with sickle cell disease (SCD). Only part of patients is able to develop alloantibodies following antigen-mismatched transfusions, named the 'immune responders', who should be prospectively transfused with antigen-matched RBC units, comprising the most immunogenic erythrocyte antigens. Auto-immune diseases are a known risk factor for RBC alloimmunization, suggesting that auto-immunity and post-transfusion alloantibody development happen through similar physiopathological pathways. In this context, polymorphisms in FCGR2B gene have already been associated with several auto-immune disorders and, hypothetically, could be associated with RBC alloimmunization and help to identify the 'immune responders' in transfusion practice. Methods: In this case-control study, we enrolled 277 transfused SCD patients with retrospective data on alloimmunization status and transfusion exposure from two Brazilian centers. DNA samples (collected from March, 2017 to June, 2018) were extracted from whole blood samples using commercial kits (PureLink™ Genomic DNA®, Invitrogen, CA), and used for PCR amplification of promoter region of FCGR2B gene containing both -386G/C and -120T/A single nucleotide polymorphisms (SNPs) using gene-specific primer. SNPs of the FCGR2B were genotyped by direct Sanger sequencing (ABI3730XL, Applied Biosystems, CA). Cases had a positive history of alloimmunization with a clinically significant alloantibody and a minimum transfusion exposure of 1 RBC unit. Controls had a negative history of alloimmunization and having received ≥ 2 RBC units. Patients with autoimmune diseases or poor quality of DNA were excluded. Unadjusted and adjusted analyses were conducted by using Logistic Regression models to determine the association of covariates with binary outcome. Since the assumption of linearity in the logit was not supported, continuous covariates were categorized based on optimum cut-off point derived from ROC analysis. All statistical analyses were performed using SAS University Edition. A p-value of <0.05 was considered to be statistically significant. Results: A total of 237 patients met the eligibility criteria, 121 cases (alloimmunized) and 117 controls (non-alloimmunized). Majority of patients were female in cases (61%) and male in controls (86%), with mean age of 27.9 years (SD 15.3). Table 1 list the characteristics between the groups. RBC alloimmunization was associated with female sex (p<0.001), lifetime number of RBC units transfused (p=0.002) and FCGR2B 120T/A SNP (p=0.031). No statistically differences in the allele frequency of c.386C were observed between groups (p=0.602). FCGR2B -386G/C and -120T/A SNPs were in intense linkage disequilibrium. Three haplotypes of promoter region were identified as 2B.1 (-386G-120T), 2B.2 (-386C-120T) and 2B.4 (-386C-120A) with statistical significance (p=0.045). Logistic regression model was performed to assess the effects of age, gender, lifetime number of RBC units transfused and FCGR2B 2B.4 haplotype on the likelihood of RBC alloimmunization in patients with SCD. The analysis identified that female sex (OR 10.03, CI95% 5.16-19.49; p<0.001) and FCGR2B 2B.4 haplotype (OR 4.55, CI95% 1.11-18.65; p=0.035) predict increased risk of RBC alloimmunization in SCD patients as show in Table 2. Conclusions: SCD patients with the FCGR2B 2B.4 haplotype had over a 4-fold higher risk for RBC alloimmunization in comparison with patients without this haplotype and probably may be helpful to identify the 'immune responders'. The presence of FCGR2B 2B.4 haplotype have been associated with increased expression of this inhibitory Fc gamma receptor in immune system cells, that was strongly associated with capacity of immune tolerance, regulating the development of antibodies. Future studies are needed to understand more about the functional and immune mechanism behind alloimmunization in SCD patients and ultimately improve our current preventive strategies. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4701-4701 ◽  
Author(s):  
Stuthi Pavani Perimbeti ◽  
Kevin Ye Hou ◽  
Sabarina Ramanathan ◽  
Adonas Woodard ◽  
Daniel Kyung ◽  
...  

Abstract Introduction: According to the National Center for Health Statistics, there was a twenty-one percent increase in deaths from drug overdose in the USA, with opioids contributing to about two-thirds of these deaths. Despite nationwide efforts to reduce opioid use, narcotic pain medications are still the most frequently used method of pain control in patients with sickle cell disease (SCD). We sought to examine the burden and complications of opioid dependence in patients with SCD. Methods: The National Inpatient Sample (NIS) for the years 1999 to 2014 was queried to yield adult admissions with a primary diagnosis of sickle cell disease (ICD-9 codes: 2826, 28260, 28261, 28262, 28263, 28264, 28268, 28269) and the admissions were stratified based on the presence of opioid dependence (ICD-9 codes: 30400-30403, 30470-30473, 30550-30553). Univariate and bivariate analyses were performed using the Chi square test. Cox proportional hazard regression was used to control for multiple confounders in calculating the hazard ratios of occurrence of complications and mortality. Results A total of 216,438 (Weighted N=1,066,536) admissions were identified between 1999 and 2014, out of which 1.6% (N=3603) had opioid dependence. The median age of patients with opioid dependence was 26 years, compared to 31 years in patients without opioid dependence. Average cost and length of hospitalization for patients with and without opioid dependence was $29,883 & $20,638 and 6.4 days & 5.1 days, respectively. The rates of various complications and Hazard Ratio (HR) of event occurrence among patients with and without opioid dependence are depicted in Table 1. After adjusting for demographics, hospital characteristics (region, bed size, location), and baseline comorbidities, SCD patients with opioid dependence had a 50% increased risk of in-hospital mortality (H.R 1.5, 95% C.I. 1.2-1.6, p<0.001) compared to those without. Conclusions: There is a correlation between opioid dependence and SCD complications among patients hospitalized with a diagnosis of SCD. Perhaps, patients predisposed to vaso-occlusive events require more frequent use of narcotics and become opioid dependent. Alternatively, the dependence on opioids may increase the incidence of complications from sickle cell disease. Regardless, patients with opioid dependence have significantly higher in-hospital mortality. The main limitation of this study is the use of ICD codes for identifying opioid dependence. In our opinion, the abnormally low incidence of opioid dependence in our data is a poor representation of the actual population. Opioid abuse is a serious concern that has heavy financial, social and public health implications on the welfare of the community, particularly those with SCD. This study highlights the need for more effective disease modifying agents for the treatment of this chronic and debilitating disorder. Disclosures No relevant conflicts of interest to declare.


PEDIATRICS ◽  
1974 ◽  
Vol 54 (4) ◽  
pp. 438-441
Author(s):  
Gerald Erenberg ◽  
Steven S. Rinsler ◽  
Bernard G. Fish

Four cases of lead neuropathy in children with hemoglobin S-S or S-C disease are reported. Neuropathy is a rare manifestation of lead poisoning in children, and only ten other cases have been well documented in the pediatric literature. The last previous case report of lead neuropathy was also in a child with hemoglobin S-S disease. The neuropathy seen in the children with sickle cell disease was clinically similar to that seen in the previously reported cases in nonsicklers, but differed in both groups from that usually seen in adult cases. It is, therefore, postulated that children with sickle cell disease have an increased risk of developing neuropathy with exposure to lead. The exact mechanism for this association remains unknown, but in children with sickle cell disease presenting with symptoms or signs of peripheral weakness, the possibility of lead poisoning must be considered.


Author(s):  
Mohamed Almuqamam ◽  
◽  
Swetha Madhavarapu ◽  
Nataly Apollonsky ◽  
◽  
...  

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.


2020 ◽  
Vol 1 (6) ◽  
pp. 175-181
Author(s):  
Raymond Mpanjilwa Musowoya ◽  
Patrick Kaonga ◽  
Alick Bwanga ◽  
Catherine Chunda-Lyoka ◽  
Christopher Lavy ◽  
...  

Aims Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia. Methods An unmatched case-control study was conducted between January and May 2019 in children below the age of 16 years. In all, 57 cases and 114 controls were obtained by systematic sampling method. A structured questionnaire was used to collect data. The different MM were identified, staged, and classified according to the Standard Orthopaedic Classification Systems using radiological and laboratory investigations. The data was entered in Epidata version 3.1 and exported to STATA 15 for analysis. Multiple logistic regression was used to determine predictors and predictive margins were used to determine the probability of MM. Results The cases were older median age 9.5 (interquartile range (IQR) 7 to 12) years compared to controls 7 (IQR 4 to 11) years; p = 0.003. After multivariate logistic regression, increase in age (adjusted odds ratio (AOR) = 1.2, 95% confidence interval (CI) 1.04 to 1.45; p = 0.043), increase in the frequency of vaso-occlusive crisis (VOC) (AOR = 1.3, 95% CI 1.09 to 1.52; p = 0.009) and increase in percentage of haemoglobin S (HbS) (AOR = 1.18, 95% CI 1.09 to 1.29; p < 0.001) were significant predictors of MM. Predictive margins showed that for a 16-year-old the average probability of having MM would be 51 percentage points higher than that of a two-year-old. Conclusion Increase in age, frequency of VOC, and an increase in the percentage of HbS were significant predictors of MM. These predictors maybe useful to clinicians in determining children who are at risk. Cite this article: Bone Joint Open 2020;1-6:175–181.


2018 ◽  
Vol 9 (7) ◽  
pp. 761-766 ◽  
Author(s):  
Hayeem L. Rudy ◽  
David Yang ◽  
Andrew D. Nam ◽  
Woojin Cho

Study Design:Sickle cell disease (SCD) is a relatively common blood disorder that has profound implications on the musculoskeletal system and particularly the spine; however, there is a paucity of data in the literature discussing this important topic.Objectives:(1) To elucidate common spinal pathologies affecting patients with SCD, as well as the medical and surgical treatments available for these patients. (2) To discuss indications for surgical management of spinal complications of SCD and important for orthopedic surgeons when taking patients with SCD to the operating room.Methods:A narrative review of the literature was performed.Results:Patients with SCD have a significantly higher risk of developing spinal pathologies including vertebral osteomyelitis, compression fracture, vertebral vaso-occlusive crises, and osteoporosis, among others. In addition, patients with sickle cell disease are particularly susceptible to developing perioperative and post-operative complications including surgical site infection, implant malfunction, and vertebral body compression fracture. Postoperatively patients with SCD are prone to developing complications and adequate hydration is necessary in order to reduce complications of SCD.Conclusions:Several spinal pathologies may arise secondary to SCD and distinguishing these pathologies from one another may be challenging due to similarities in symptoms and inflammatory markers. Although most patients with SCD can benefit from conservative treatment involving rest, symptomatic therapy, antibiotic therapy, and/or orthosis, surgical intervention may be indicated in certain cases. It is preferable to avoid surgery in patients with SCD due to an increased risk of complications such as wound infection and vaso-occlusive crisis.


Author(s):  
David Rees

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.


2019 ◽  
Vol 8 (11) ◽  
pp. 1839
Author(s):  
Madhi ◽  
Kamdem ◽  
Jung ◽  
Carlier-Gonod ◽  
Biscardi ◽  
...  

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.


2019 ◽  
Vol 08 (01) ◽  
pp. e1-e4 ◽  
Author(s):  
Malgorzata Gozdzik ◽  
Sergio Mariotti ◽  
Michele Genoni ◽  
Alicja Zientara

Background Homozygous sickle cell disease (SCD) compounded with bacterial endocarditis makes open-heart surgery a multidisciplinary challenge. Case description A 45-year-old African male patient with homozygous SCD presented with right heart decompensation, tricuspid regurgitation, and endocarditis of the aortic valve. Blood coulters were positive for coagulase-negative staphylococci. An emergent double valve replacement was successfully performed involving a multidisciplinary team. Conclusion Homozygous SCD is associated with an increased risk of preoperative vaso-occlusive complications. Surgery with cardiopulmonary bypass can be performed, if hypothermia, hypoxia, acidosis, or low-flows are being avoided. Due to the lack of data, the adequate approach is still intuitive and requires standardization.


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