Survival of Children with Sickle Cell Disease: An Update from the Dallas Newborn Cohort.

Abstract The Dallas Newborn Cohort is the largest newborn inception cohort of individuals who have sickle cell disease (SCD), and it has provided modern pediatric SCD survival data (Blood2004;103:4023–7). The Cohort includes subjects who were diagnosed at birth by universal newborn screening and followed at our center up to 18 years of age. All subjects with sickle cell anemia (SS) or sickle-β° thalassemia (Sβ°) were prescribed prophylactic penicillin until 5 years of age. The first report from the Cohort showed an overall survival of 85.6% at 18 years for individuals with SS or Sβ°. The standard error of this estimate was high because only 8 individuals remained at risk at 18 years of age at the time of the analysis, which included follow-up until July 2002. Accrual and follow-up of cohort members has continued. We therefore sought to update the survival estimates through age 18 by including three further years of follow-up. By definition the Dallas Newborn Cohort includes all individuals with SS, Sβ°, sickle-hemoglobin C disease (SC), or sickle-β+-thalassemia (Sβ+) who were born in Texas after November 1, 1983, diagnosed by the newborn screening program of Texas, and seen at least once in our center. New members of the Cohort who came to our center between July 2002 and July 2005 were identified. Follow-up of existing members was updated. All deaths and their causes were determined. Subjects were analyzed in two separate groups because of known clinical similarities: SS/Sβ° and SC/Sβ+. Overall survival was analyzed by the Kaplan-Meier method. Subjects were censored at the time of their last clinical encounter. We identified 115 new subjects, and included 1627 additional patient-years of follow-up. The cohort now includes 826 subjects (SS 503, Sβ° 18, SC 247, Sβ+ 58; male:female 427:399) and it provides 7275 patient-years of follow-up. Mean follow-up was 8.9 years (range 0.9–19.5 years). 62 patients (7.5%) were lost to follow-up. There were 25 deaths in the cohort; none was new and all were previously reported. Of the deaths, 15 were likely related to SCD (5 sepsis, 3 acute chest syndrome, 2 multi-organ failure syndrome, 5 other) and 10 were apparently unrelated to SCD (4 trauma or accidental death, 6 other diseases). There were 22 and 3 deaths in the SS/Sβ° and SC/Sβ+ groups, respectively. All the SC/Sβ+ deaths were apparently unrelated to SCD. Overall survival at 18 years for SS/Sβ° and SC/Sβ+ subjects was 92.4% (standard error [SE] 1.9; 52 at risk) and 98.1% (SE 1.3; 12 at risk), respectively. The overall incidence of death through 18 years of age was 0.46 and 0.12 per 100 patient-years, respectively. In conclusion, this updated survival analysis of the Dallas Newborn Cohort now shows that over 90% of children with SS/Sβ° survive childhood, and nearly 100% of children with SC/Sβ+ become adults.

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Improved Survival of Children and Adolescents with Sickle Cell Disease.

Blood ◽

10.1182/blood.v112.11.1425.1425 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1425-1425

Author(s):

Charles T. Quinn ◽

Kimberly Thomas ◽

Zora R. Rogers ◽

George R. Buchanan

Keyword(s):

Overall Survival ◽

Young Adults ◽

Sickle Cell Disease ◽

Organ Failure ◽

Sickle Cell ◽

Adolescents And Young Adults ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Multi Organ Failure

Abstract The survival of children with sickle cell disease (SCD) has improved over the past several decades, especially for very young children. However, we know less about mortality during adolescence, and we do not accurately know the current proportion of children born with SCD who survive to adulthood. The first report from the Dallas Newborn Cohort (DNC), which included follow-up through June 2002, estimated overall survival at 18 years of age to be 85.6% (95% C.I.: 73.4 – 97.8) for individuals with sickle cell anemia (SS) or sickle-β0-thalassemia (Sβ0) (Blood2004;103:4023–7). The confidence interval of this estimate was wide because only 8 cohort subjects were 18 years old at the time. Here we update the survival analysis with 5 more years of accrual and follow-up to provide an accurate, contemporary estimate of mortality for patients with SCD through 18 years of age. The DNC includes all individuals with SS, Sβ0, sickle-hemoglobin C disease (SC), or sickle-β+-thalassemia (Sβ+) who were diagnosed by the newborn screening program of Texas (initiated November 1, 1983) and seen at least once in our center. Subjects were analyzed in two separate groups because of clinical similarity: SS/Sβ0 and SC/Sβ+. Overall survival was analyzed by the Kaplan-Meier method. Subjects were censored at the time of their last clinical encounter. Between July 2002 and July 2007 we identified 229 new members of the DNC and added 3,201 additional patient-years of follow-up. The cohort now includes 940 subjects (572 SS, 284 SC, 63 Sβ+, 21 Sβ0; 52.8% male), and it provides a total of 8,857 patient-years of follow-up (5,819 SS/Sβ0 patient-years, 3,039 SC/Sβ+ patient-years). Mean follow-up is 9.4 years (range 0.1– 20.6 years), and 97 subjects are now at least 18 years of age at last follow-up. To date, 92 subjects (9.8%) have been lost to follow-up (not seen for >5 years), and 33 subjects have died (30 SS/Sβ0, 3 SC/Sβ+). There were 7 new deaths in DNC patients since 2002, all of which occurred in patients who were 18 years of age or older. Of all deaths, 23 were SCD-related (5 acute chest syndrome, 5 sepsis, 4 multi-organ failure syndrome, 9 other), and 10 were apparently unrelated to SCD (4 trauma or accidental death, 6 unrelated medical conditions). All SC/Sβ+ deaths were apparently unrelated to SCD. Overall survival at 18 years was 93.9% (95% C.I. 90.3 – 96.2; 81 patients > 18 years of age) for SS/Sβ0 subjects and 98.4% (95% C.I. 94.4 – 99.5; 16 patients > 18 years) for SC/Sβ+ subjects. The overall incidence of death in the SS/Sβ0 and SC/Sβ+ subgroups was 0.52 and 0.10 per 100 patient-years, decreased from 0.59 and 0.24 in the original DNC analysis. Survival also appears to be improving across cohort eras (Figure). In conclusion, approximately 6% of children with SS or Sβ0 die during childhood, but almost all children with SC or Sβ+ live to become adults. Although early childhood mortality has greatly decreased, we show that many adolescents and young adults still die from SCD. Notably, acute chest syndrome and multi-organ failure have now surpassed sepsis as the leading causes of death. These data provide the accurate, contemporary foundation for the counseling of parents of newborns with SCD and for genetic counseling for prospective parents. Finally, given the marked decrease in early mortality we show here, new efforts to improve survival in SCD should focus on adolescents and young adults. Figure Figure

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Sickle Cell Disease: Management options and challenges in developing countries

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2013.062 ◽

2013 ◽

Vol 5 (1) ◽

pp. e2013062 ◽

Cited By ~ 23

Author(s):

Daniel Ansong ◽

Alex Osei-Akoto ◽

Delaena Ocloo ◽

Kwaku Ohene-Frempong Ohene-Frempong

Keyword(s):

Developing Countries ◽

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

Health Care Professionals ◽

Genetic Disorder ◽

Sub Saharan Africa ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Management Options

Sickle Cell Disease (SCD) is the most common genetic disorder of haemoglobin in sub-Saharan Africa. This commentary focuses on the management options available and the challenges that health care professionals in developing countries face in caring for patients with SCD. In developing countries like Ghana, newborn screening is now being implemented on a national scale. Common and important morbidities associated with SCD are vaso-occlusive episodes, infections, Acute Chest Syndrome (ACS), Stroke and hip necrosis. Approaches to the management of these morbidities are far advanced in the developed countries. The differences in setting and resource limitations in developing countries bring challenges that have a major influence in management options in developing countries. Obviously clinicians in developing countries face challenges in managing SCD patients. However understanding the disease, its progression, and instituting the appropriate preventive methods are paramount in its management. Emphasis should be placed on newborn screening, anti-microbial prophylaxis, vaccination against infections, and training of healthcare workers, patients and caregivers. These interventions are affordable in developing countries.

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A North American Experience Of Hemoglobin SC Disease, Its Complications, and Management

Blood ◽

10.1182/blood.v122.21.2221.2221 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2221-2221 ◽

Cited By ~ 1

Author(s):

Veronique Naessens ◽

Richard Ward ◽

Kevin H.M. Kuo

Keyword(s):

Sickle Cell Disease ◽

Avascular Necrosis ◽

Sickle Cell ◽

Care Center ◽

Comprehensive Care ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Baseline Hemoglobin ◽

Hemoglobin Sc Disease

Background The phenotype of hemoglobin SC (HbSC) disease is distinct from sickle cell anemia (SCA) (HbSS and S/b0) but management of adults is mostly derived from studies of the latter group. Longitudinal observational studies on the complications and outcomes of hemoglobin SC disease are largely confined to centers outside North America. The unique ethnic composition of our cohort, consisting of mostly Western Africans and West Indians, permits further characterization of the HbSC phenotype. Objective to describe the baseline characteristics and long-term complications of a cohort of adult HbSC patients followed in a Canadian sickle cell comprehensive care center. Methods A retrospective observational cohort study was conducted on all adult patients with HbSC disease attending a sickle cell comprehensive care center in Toronto, Canada from 1994 to 2013. Baseline demographics, acute and chronic complications attributable to sickle cell disease, and laboratory data were collected. Medians were used to describe continuous variables, while percentages or ratios for categorical variables. Logistic regression was used to examine factors influencing the main clinical complications. Results 104 patients were included in the analysis, comprising of 38.5% males and 61.5% females. Median length of follow-up was 3.5 years (1 - 19) and median age at last recorded visit was 35 years (18 - 68). Median baseline hemoglobin was 119 g/L (82 - 153 g/L), hematocrit 0.340 (0.250 - 0.440), and fetal hemoglobin (HbF) fraction 1% (0 - 7.7%). Most frequent complications encountered were retinopathy (55.8%) and symptomatic avascular necrosis (27.9%), followed by painful vaso-occlusive crises requiring emergency room visit (23.1%). Presence of retinopathy was associated with higher baseline hemoglobin (OR 2.72 for every 10 g/L of hemoglobin, p = 0.037) and older age (OR 2.72 for every decade, p < 0.001). Acute chest syndrome (7.7%), priapism (7.5% of men), and renal involvement (8.2%), were less common than reported in the literature, while the rates of venous thromboembolism (8.7%), symptomatic infarctive or hemorrhagic stroke (2.9%) were slightly more common. Median right ventricular systolic pressure on 2D-transthoracic echocardiogram was 29 mmHg (17 – 43 mmHg). No patient underwent a right heart catheterization. Two patients died from septic shock, both at the age of 29. Disease-modifying therapy most often consisted of hydroxyurea (28.8%), followed by exchange transfusion (6.7%) and phlebotomies (5.8%). Hydroxyurea significantly increased the median HbF fraction (from 1% to 2.75%, p = 0.004 by related-samples Wilcoxon signed rank test). Conclusion In this large North American cohort of adult patients, we have again shown that HbSC disease is not as benign as traditionally thought. As such, patients with HbSC disease warrant similar follow-up to that provided to SCA. Retinopathy, avascular necrosis and painful vaso-occlusive crises were the most common complications in our study, albeit lower than in other reported cohorts. The frequent use of hydroxyurea in this cohort is quite unique compared to other sickle cell comprehensive care centers reported in the literature. However, therapeutic phlebotomy is less often used compared to the European experience. We also observed a lower frequency of retinopathy, avascular necrosis, painful vaso-occlusive crises, priapism and acute chest syndrome. Whether this observation is due to hydroxyurea use or to other genetic or environmental factors remains to be determined. Further studies are also required to develop a more evidence-based therapeutic strategy for this genotype of Sickle Cell Disease. Disclosures: No relevant conflicts of interest to declare.

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Incidence and Risk of Delayed Hemolytic Transfusion Reaction in Sickle Cell Disease Patients Based on a Prospective Study

Blood ◽

10.1182/blood.v128.22.95.95 ◽

2016 ◽

Vol 128 (22) ◽

pp. 95-95 ◽

Cited By ~ 1

Author(s):

France Pirenne ◽

David Narbey ◽

Philippe Chadebech ◽

Armand Mekontso-Dessap ◽

Pablo Bartolucci ◽

...

Keyword(s):

Sickle Cell Disease ◽

Prospective Study ◽

Sickle Cell ◽

Acute Chest Syndrome ◽

Transfusion Reaction ◽

Cell Disease ◽

Hemolytic Transfusion Reaction ◽

Delayed Hemolytic Transfusion Reaction ◽

Prospective Longitudinal

Abstract Background Delayed hemolytic transfusion reaction (DHTR) is a life threatening complication of transfusion in sickle cell disease (SCD). This syndrome is underestimated because of a clinical picture that resembles a vaso-occlusive crisis (VOC) and the frequent absence of detectable antibodies. Several retrospective studies have evaluated the frequency of DHTR based on case reports. We conducted a prospective, longitudinal, single center study to determine the incidence of DHTR and the risk of developing DHTR depending on the transfusion regimen: chronic versus punctual. Methods and patients SCD patients aged over 18 years, undergoing a transfusion, were enrolled in this study. A total of 697 transfusion episodes (TE) in 312 patients were included during 30 months. Some patients had multiple TE during the period. The post transfusion outcome of the patients was assessed up to one month after the included TE. DHTR was confirmed based on the rapid disappearance of HbA (> 50% 15 days post-transfusion) associated with two of the following criteria up to three weeks after transfusion: VOC symptoms, dark urine, worsening anemia, increased LDH. Transfusion episodes were divided into chronic (336 TE in 111 patients) and punctual (361 TE in 201 patients). Chronic transfusions were defined as regular transfusions to treat chronic complications or for primary/secondary prevention of complications. Short transfusion program during pregnancy was considered as punctual transfusions if patients were not previously regularly transfused. The study obtained approval of the local Ethics Committee. Results Follow-up of the patients after transfusion showed 15 DHTR during the study. They all developed in punctually transfused patients. Thus, patients who are transfused punctually have a significantly higher risk of developing DHTR than those in a regular transfusion program (p < 0.001). When considering only punctual transfusions, the incidence of DHTR is 4.2% per transfusion episode (IC 95% [2.6; 6.9]) and 7.5% per patient during the 30 months of the study (IC 95% [4.6; 12.4]). In these DHTR cases, the transfusion indication was surgery (n = 6), pregnancy (n = 3), acute chest syndrome (n = 3), stroke (n = 1), profound anemia (n = 1), and VOC prevention before a school exam (n = 1 case). Two patients died of multi-organ failure following severe intravascular hemolysis. The median hemoglobin decrease for all DHTR cases after the triggering transfusion was 4.4 g/dl [IQR 3.6-5.2]; the highest LDH level was 879 [IQR 680-1423]. Ten patients developed newly formed antibodies, but only five among them displayed antibodies with significant serological features (anti-Fya, anti-S, anti-Jka, anti-HI). In the five other cases, the antibodies were of unspecified specificity or auto antibodies in the RH blood group (the genetic RH background was known). Finally, antibodies were undetectable for five cases, confirmed by long-term patient follow up. Conclusion This prospective study demonstrates, for the first time, that DHTR is a frequent reaction in adult SCD patients, developing only in occasionally transfused patients. This finding highlights that adult patients with regular transfusion who did not previously encountered DHTR are not susceptible to developing this severe reaction. A mechanism linked to acute situations can be suggested as already shown for the induction of allo-immunization. However, many cases developed without detectable antibodies, confirming the complex pathophysiology of this syndrome. A bio-clinical scoring system to predict DHTR, based on this study, is under development and will be presented. Disclosures Michel: Roche: Research Funding.

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Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽

10.1182/blood.v97.11.3628 ◽

2001 ◽

Vol 97 (11) ◽

pp. 3628-3632 ◽

Cited By ~ 132

Author(s):

Alina Ferster ◽

Parvine Tahriri ◽

Christiane Vermylen ◽

Geneviève Sturbois ◽

Francis Corazza ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

History Of ◽

Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

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Cumulative Incidences and Risk Factors for Intra and Extracranial Cerebral Arteriopathy in Sickle Cell Disease Children

Blood ◽

10.1182/blood-2020-136089 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 56-57

Author(s):

Francoise Bernaudin ◽

Suzanne Verlhac ◽

Cécile Arnaud ◽

Annie Kamdem ◽

Isabelle Hau ◽

...

Keyword(s):

Risk Factors ◽

At Risk ◽

Risk Factor ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cumulative Incidence ◽

Intracranial Stenosis ◽

Cell Disease ◽

Independent Risk Factors

In children with sickle cell disease (SCD), cerebral vasculopathy is responsible for overt strokes and silent cerebral infarcts (SCI). Transcranial Doppler (TCD) detects children at risk of strokes (intracranial time averaged mean of velocities (TAMV) ≥200cm/s). The extracranial portion of the internal carotid artery (eICA) can also be the site of stenosis or occlusion. eICA assessment requires cervical Doppler using a submandibular approach and cervical MRA (cMRA). We previously reported that eICA TAMV≥160cm/s are highly predictive of eICA stenosis and are a risk factor for SCI independently of acute and chronic anemia. However, the kinetics of eICA arteriopathy are unknown. The aim here was to evaluate and compare the cumulative incidence of intra/extracranial arteriopathy and associated risk factors in a longitudinal SCD cohort. Children born between 01/1988 and 01/ 2018, followed at our center at least until 06/2012 and up to 09/2019, annually assessed by TCD imaging and at least once by cervical Doppler were included, resulting in 493 SCD children (238F-255M) with 398 SCA (385SS,10Sb0,3SDPunjab), and 95 SC/Sb+ children (65SC,30Sb+). Alpha-genes, b-globin haplotypes, G6PD activity, CD36 expression were recorded. The average of baseline biologic parameters recorded between 1 and 3 years of age, a minimum of 3 months away from transfusion, 1 month from a painful episode, and before any intensive therapy was calculated. The median (range) follow-up of the overall cohort was 10.6 years (1.1-22.9), providing 5335 patient-years of follow-up. Six deaths occurred (5 SCA-children at 2, 4, 7, 19 & 20 years and 1 in SB+ patient at 13 years). Three SS patients had an ischemic stroke at 1.5, 3 and 4.3 years. Kaplan-Meier estimates of cumulative incidence (95%CI) are shown (Figure). In SCA-children, abnormal eICA TAMV and/or eICA stenosis were sometimes associated with abnormal intracranial TAMV and/or stenosis, but isolated eICA TAMV≥200cm/s or 160-199cm/s were observed in 19 (4.8%) and 28/398 (7.0%) patients, respectively, and isolated eICA stenoses in 33/294 (11.2%).Thus, risk factors were only analyzed in patients with isolated intra- or extracranial arteriopathy. COX regression analyses are shown (Table). For isolated intracranial TAMV≥200cm/s, multivariate analyses after introducing all significant genetic and biological risk factors retained the number of SEN b-haplotypes [HR=0.547 (95%CI:0.335-0.893); p=0.016], reticulocyte count>400x109/L [HR=1.961 (95%CI:1.119-3.436); p=0.019], and WBC count>20x109/L [HR=2.410 (95%CI:1.340-4.329); p=0.003] as independent risk factors. Isolated eICA TAMV≥160 cm/s were only strongly associated with the presence of tortuosities [HR=8.6 (95%CI :4.3-17.2); p<0.001]. eICA tortuosities were present in 94/284 (33.1%) SCA vs 5/43 (11.6%) SC/Sb+ children (p=0.004), most often seen at the first cMRA but secondarily in 16 patients. Multivariate COX analysis retained genotype [HR/SCA vs SC/Sb+ = 3.6 (95%CI:1.4-9.4); p=0.010], low hemoglobin [HR=1.25 (95%CI:1.04-1.50); p=0.020], and high LDH [HR=1.002 (95%CI:1.001-1.002); p=0.001], as independent risk factors for eICA tortuosities. As expected, the risk of intracranial stenosis was significantly associated with isolated intracranial TAMV≥200 cm/s [HR (95%CI)=4 .255 (2.146-8.475); p<0.001]. After adjustment with isolated intracranial TAMV≥200 cm/s, a-thalassemia, low hemoglobin, high WBC, MCV and LDH remained as significant, but not independent, risk factors for intracranial stenosis. The risk for eICA stenosis was only highly associated with the presence of tortuosities [HR=10.9 (95%CI:4.7-25.0); p<0.001], or a history of eICA≥160cm/s [HR=15.4 (95%CI :7.5-31.2); p<0.001]. This study reports eICA arteriopathy kinetics using a longitudinal cohort of SCD children systematically assessed by Doppler and cMRA. While we confirm that only SCA and not SC/Sb+ children are at risk of intra/extracranial arteriopathy, we show for the first time that extracranial arteriopathy progressively develops as early as 2 years old in SCA-children and reaches a plateau around 10 years of age, as for intracranial arteriopathy. Furthermore, eICA tortuosities, which are the risk factor for eICA arteriopathy, are themselves significantly and independently associated with the SCA genotype and the severity of hemolytic anemia. Figure Disclosures Bernaudin: BlueBirdBio: Consultancy; AddMedica: Honoraria, Other; GBT: Membership on an entity's Board of Directors or advisory committees. Verlhac:BlueBirdBio: Consultancy; AddMedica: Honoraria.

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PUBLIC PRESENTATIONS

PEDIATRICS ◽

10.1542/peds.83.5.910 ◽

1989 ◽

Vol 83 (5) ◽

pp. 910-910

Author(s):

Deborah D. Henry

Keyword(s):

New York ◽

New York City ◽

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

York City ◽

Screening Program ◽

Newborn Screening Program ◽

Cell Disease

I am the parent of an 11½-year-old daughter with sickle cell disease. I am aware of the need for a comprehensive newborn screening program for sickle cell disease and other hemoglobinopathies. However, all such programs must be instituted with a follow-up component, and parents should be made aware that such screenings are being done. My daughter was born during the summer of 1975 in New York City. New York City began screening for sickle cell and similar hemoglobinopathies in May 1975, but had no comprehensive follow-up program until 1978. My daughter was not screened nor was I aware of the screening program. I learned of my daughter's condition during a routine well-child clinic visit when she was 6 months of age. I am afraid to think of her outcome had I not been taking her for preventive health care, because before the age of 1 year she experienced one of the most life-threatening crises of a child with sickle cell disease—splenic sequestration. I am pleased to announce that in New York City today, parents are notified in a timely manner of their infant's newborn screening results with information regarding follow-up and counseling services. Two of my immediate family members gave birth to infants with sickle cell trait. They were informed of their infants' results within 2 weeks after their babies' births, and were given concrete information and recommendations for follow-up genetic services. I know a comprehensive newborn screening program will prevent mortality in infants found to have sickle cell disease and related hemoglobinopathies.

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Newborn Screening for Sickle Cell Disease

PEDIATRICS ◽

10.1542/peds.83.4.629a ◽

1989 ◽

Vol 83 (4) ◽

pp. 629-630

Author(s):

THOMAS GROSS

Keyword(s):

Sickle Cell Disease ◽

Newborn Screening ◽

Sickle Cell ◽

Critical Review ◽

Progression of Pulmonary Hypertension in Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3187.3187 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3187-3187 ◽

Cited By ~ 3

Author(s):

Kenneth I. Ataga ◽

Charity Moore ◽

Susan Jones ◽

Oludamilola Olajide ◽

Dell Strayhorn ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Left Ventricular ◽

Right Atrial ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Original Cohort ◽

The Mean

Abstract Introduction: The prevalence of pulmonary hypertension (PHT) is high in patients with sickle cell disease (SCD). Although most patients have only mild increases in their pulmonary artery systolic pressure (PASP), the presence of PHT is strongly associated with an increased risk of death. While PHT seen in SCD is thought to progress over time, both the rate of development of PHT and the factors that affect disease progression remain unknown. Methods: The 41 subjects in this study were drawn from an original cohort of 60 patients followed in the Sickle Cell Clinic at UNC-Chapel Hill. All patients were previously evaluated for PHT (defined using an age-, sex-, and BMI-adjusted reference range). Of the 60 patients in the original cohort, six are now deceased and 13 others were not available for repeat evaluation. The PASP was determined using Doppler echocardiography and then applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure). Individuals were not studied if they: 1) showed clinical evidence of left ventricular failure; 2) had a recent acute illness (e.g., vaso-occlusive crisis); or 3) had experienced an episode of acute chest syndrome within the preceding 4 weeks. Means and standard deviations were calculated for all measures at the time of initial evaluation and at the time of follow-up. Results: Of the 41 subjects in our study, PHT was originally present in 12, while no evidence of PHT was present in 29. Of the 29 subjects who initially had no evidence of PHT, 4 (or 14%) have now developed PHT (mean follow-up period of 3.3 ± 0.4 years). In these 4 subjects, the mean PASP at the time of initial and follow-up evaluations respectively were: 37.0 ± 2.0 mm Hg vs. 55.8 ± 11.0 mm Hg. The patients who developed PHT during the course of the study had lower systolic BP (143 ± 12 mm Hg vs. 128 ± 12 mm Hg), lower fetal hemoglobin levels (6.2 ± 5.7 % vs. 4.2 ± 3.7 %), and higher platelet counts (276 ± 119 X 103/μL vs. 426 ± 96 X 103/μL) at the time of their follow-up analyses. By contrast, 3 of the 12 subjects (or 25%) who were thought to have PHT at the time of their original evaluations were found to have normal PASP determinations at the time of their repeat echocardiograms (mean follow-up period of 3.2 ± 0.6 years). In these latter 3 subjects, the mean PASP values at the time of the initial and follow-up evaluations respectively were: 40.0 ± 4.6 mm Hg vs. 33.7 ± 4.7 mm Hg. Conclusion: In this small group of patients with SCD, we found that PHT developed in 14% of subjects who had no evidence of PHT 3 years earlier. Based on this observation, it seems that periodic echocardiograms to screen for the development of PHT would be appropriate. On the other hand, our observation that some patients initially classified as having PHT failed to have elevated PASP measurements at the time of follow-up illustrates the limitation of a single echocardiographic evaluation in establishing this diagnosis. Because of the increase in PASP that occurs during acute vaso-occlusive episodes, and the difficulty usually encountered in distinguishing steady state from crisis, the initial elevation of the PASP in these patients could have resulted from sub-clinical crisis states. For these reasons, a patient found to have an elevated PASP at the time of a screening echocardiogram should have a repeat study, and perhaps a right heart catheterization, before the diagnosis of PHT is firmly established.

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Predictors of Adverse Outcomes in Hospitalized Adult Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3197.3197 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3197-3197

Author(s):

Fahd Rahman ◽

Roy N. Gay ◽

Samir K. Ballas ◽

Juan C. Zubieta ◽

Zekarias Berhane ◽

...

Keyword(s):

At Risk ◽

Logistic Regression ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Acute Pain ◽

Reticulocyte Count ◽

Laboratory Data ◽

Adverse Outcomes ◽

Acute Chest Syndrome ◽

Cell Disease

Abstract The identification of patients with sickle cell disease at risk of serious complications at the time of hospital admission can help stratify patients who will need aggressive management. We identified predictors associated with adverse outcomes such as frequent hospitalizations, acute pain crises and acute chest syndromes. To that end, we retrospectively reviewed medical records of 265 adult sickle cell disease patients, hospitalized between 1/1/98 and 2/3/05 at Mercy Catholic Medical Center, with complete clinical and laboratory data. 195/73.6% had HbSS and the rest had HbSC, HbSβ-thal0,HbS-βthal+or HbSOarab disease. 59 variables were considered including demographic, hematological, biochemical, clinical and treatment data. Logistic regression models were used to obtain associations between variables, and to adjust for confounding effects. Analysis showed that adverse events during admission included acute pain crises in 249/94%, acute chest syndromes in 25/9.4% and strokes in 5/1.9% patients. Other outcomes were a greater than 2 hospitalizations per year 82/31.9%, more than 2 pain crises per year 145/54.7%, transfusion required during admission 72/27.2%, length of hospital stay more than 5 days 105/39.6% and death during hospitalization 13/4.9%. Multivariate logistic regression analysis revealed 21 factors with statistically significant associations. A reticulocyte count greater than 1.5 (OR 3.98, CI 1.48–10.69, P.006) and employment status (OR .31, CI .13-.75, P.009) were associated with more admissions per year. History of acute chest syndrome (OR 5.33, CI 1.7–16.77, P.004), reticulocyte count greater than 1.5 (OR 3.46, CI .91–13.11, P.067) and care provided by a nonhematologist (OR 5.04, CI 1.7–14.95, P.0035) were linked with more pain crises per year. Pain crises during admission were associated with HbSS disease (OR 9.31, CI 2.17–39.9, P.01) and out patient folate therapy(OR 6.23, CI 1.45–26.84, P.003). Patients with leukocytosis (OR 3.41, CI 1.2–9.67, P.02) and a higher serum glucose level (OR 7.54, CI 2.6–21.86, P.0002) were linked to more acute chest syndromes. Females (OR .1, CI .03–.37, P.0004) were at lower risk of having acute chest syndromes. Outpatient folate therapy (OR .07, CI .007–.69, P.02) was associated with lower numbers of acute neurological events. Patients with initial hemoglobin levels less than 7 g/dL (OR 1.99, CI 1–4, P.0007) and prolonged hospitalization (OR 7.06, CI 3.63–13.74, P.0001) frequently required transfusions. Variant diseases (OR .28, CI .13–.58, P.05) required fewer transfusions. Deaths during hospitalization were lower with folate therapy (OR .18, CI .05–.63, P.007) and a transfusion requirement during admission (OR 5.07, CI 1.45–17.64, P.01) predicted more deaths. HbSS patients (OR 2.52, CI 1.1–5.8, P.03), substance abusers (OR 2.93, CI 1.21–7.08, P.01), those requiring antihistamines during admission (OR 3.33, CI 1.38–8.03, P.007), or requiring more than 2 hospitalizations per year (OR 2.62, CI 1.26–5.43, P.009) had hospital stays longer than 5 days while in females odds were low for this outcome (OR .30, CI .15–.59, P.0005). In conclusion, simple tools like a complete history, physical examination, demographic and laboratory data can help clinicians and health care providers to gauge severity of the illness and deliver tailored management protocols targeting these “at risk” sickle cell disease patients.

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