Studies examine quality of care for hospitalized sickle cell disease patients

Johns Hopkins researchers have used fruit flies to gain new insights into a brain-damaging disorder afflicting children. Their work suggests a possible therapy for the disease, for which there is currently no treatment. The researchers genetically modified flies to exhibit symptoms of mucolipidosis type IV (ML4), a disease in which nerve cells in the brain

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A study assessing the quality of care for patients with sickle cell disease in a variety of hospital settings was presented Saturday, December 6 during the 50th Annual Meeting of the American Society of Hematology in San Francisco, CA.

Two other studies on screening methods that help determine stroke risk in children with sickle cell disease, as well as a study examining the effects of long-term hydroxyurea use in adult patients with the disease, will also be presented.

“The studies highlighted in this press conference showcase important advances in our understanding of sickle cell disease,” said Nancy Berliner, MD, 2009 ASH President and Chief of Hematology at Brigham and Women’s Hospital in Boston. “These studies highlight observations and interventions aimed at reducing complications and mortality from sickle cell disease in both children and adults.”

In addition, the press conference will provide a preview of the new hematology documentary “Blood Detectives,” which will premiere on the Discovery Health cable network on December 19, 2008, at 7:00 p.m. ET/PT and again at 12:00 midnight. The show focuses on hematologists as they work to unravel medical mysteries and save lives. One of the key stories featured is that of Alexandria, a teenage girl being treated for sickle cell anemia who previously suffered a silent stroke; her hematologist, Michael DeBaun, MD, who is featured in the film, along with Dr. Berliner, who was a scientific advisor for the documentary, are co-moderators of this press briefing.

“Stroke is a serious consequence of sickle cell anemia,” said Dr. DeBaun, Director, Sickle Cell Medical Treatment and Education Center, St. Louis Children’s Hospital, Washington University Medical School, St. Louis, MO. “Finding innovative ways to detect the risk of stroke in children like Alexandria is essential to improving the survival and quality of life of patients with this disease.”

Healthy red blood cells are flexible so that they can move easily through the smallest blood vessels. In sickle cell disease, the hemoglobin carried by the red blood cells is abnormal, causing the cells to become rigid, sickle-shaped, and more likely to become stuck in the blood vessels, blocking blood flow. This blockage can cause pain and infections and, when blood flow to specific organs is affected, can also lead to stroke, acute chest syndrome (a life-threatening condition affecting the blood vessels in the lungs), organ damage, and blindness.

Sickle cell disease affects approximately 100,000 Americans each year and is responsible for 100,000 hospitalizations each year at the cost of $500 million. The average life expectancy of a person with the condition is around 40 years of age according to the Sickle Cell Disease Association of America. Recognizing the deadly impact of sickle cell disease, the American Society of Hematology teamed with Discovery Health and award-winning filmmaker Joseph Lovett on “Blood Detectives,” which is the cornerstone of a new public awareness campaign, Blood: The Vital Connection (, designed to educate the public about this and other common blood conditions.

Quality of Care in Hospitalizations for Sickle Cell Disease in the U.S.: Do Low Patient Volumes Mean Higher Mortality? [Abstract #166]
Timothy L. McCavit, MD, The University of Texas Southwestern Medical Center, Dallas, TX

This study assessed the quality of care of hospitalized patients with sickle cell disease in a variety of hospital settings and showed that hospitals that treat a small number of patients with sickle cell disease have significantly higher mortality rates than hospitals that treat a larger volume. The findings suggest that the identification of specific factors associated with reduced mortality, including greater adherence to standards of care and clinical practice guidelines, has the potential to reduce morality at hospitals that treat a small number of patients with sickle cell disease. The study also shows that lack of insurance coverage is also associated with higher mortality and shorter hospital stays.

Data on sickle-cell-related hospitalizations from the National Inpatient Sample, which included hospitalization records from approximately 8 million hospitalizations annually from 1,000 hospitals in 37 states from 2003 to 2005, were examined to determine whether three potential determinants of quality care - hospital volume, hospital teaching status, and patient socioeconomic status - are associated with three quality indicators, including length of hospital stay, cost of hospitalization, and mortality for hospitalized patients with sickle cell disease. A total of 70,748 hospital discharges of sickle cell disease patients were identified and analyzed. Of these visits, the average length of stay was four days, costing an average of $4,100 per hospitalization. The analysis identified 425 deaths associated with sickle cell disease, translating into a mortality rate of six deaths per every 1,000 sickle cell hospitalizations.

A multivariable analysis, controlling for severity of illness and several other factors, confirmed that a lower volume of sickle cell patients was associated with significantly increased mortality and a decreased length of hospital stay. Additionally, self-pay status for insurance type was associated with increased mortality and a decreased length of hospital stay. Teaching hospitals had a higher adjusted cost of care for all patients but a decreased length of adult hospital stays. There was no significant association between mortality and hospital teaching status. Patient socioeconomic status was not associated with length of hospital stay or cost; however, lower status trended toward higher mortality in adult patients with sickle cell disease.

Transcranial Doppler Screening Program Is Effective in Preventing Stroke in Children With Sickle Cell Disease [Abstract #714]
Janet K. Kwiatkowski, MD, Children’s Hospital of Philadelphia, Philadelphia, PA

Childhood stroke is one of the most devastating complications of sickle cell disease. Although the use of transcranial Doppler ultrasonography (TCD) has become routine for screening children with sickle cell disease at high risk for stroke, the impact of the screening tool on the overall incidence of stroke in these patients had not been extensively studied until now. This study found that the use of TCD, coupled with the use of preventive transfusion treatments, has been highly successful in reducing the rate of primary stroke in children with the disease.

In this study, the researchers compared the rate of stroke in the eight-year period after TCD screening began at the Children’s Hospital of Philadelphia with that of the eight-year period prior to the implementation of TCD screening. The current protocol for TCD screening at the Children’s Hospital includes annual TCD screening for children with normal TCD results (indicated by a cerebral blood-flow velocity of less than 170 cm/s in the internal carotid and middle cerebral arteries), repeat screening every three to six months in children with conditional TCD results (between 170 and 199 cm/s), and every one to four weeks in children with abnormal TCD results (greater than or equal to 200 cm/s). Transfusion therapy is recommended for all children with confirmed abnormal TCD.

A total of 475 children who were followed for a cumulative total of 3,137 person-years (the total sum of the number of years that each child was observed) were part of the pre-TCD group, and 530 children who were followed for a cumulative total of 3,578 person-years were part of the post-TCD group. Cases of stroke or other neurological events were identified from the clinical database, reviewed by the study neurologist, and classified into one of three categories: overt stroke (ischemic or hemorrhagic), not overt stroke (other neurological event), and indeterminate (unable to classify based on available information). Incidence rates for stroke were calculated and compared between the pre-TCD and post-TCD groups.

The study found that the incidence of overt stroke in the pre-TCD group was significantly higher compared to the post-TCD group (0.67 per 100 years compared with an incidence of 0.06 per 100 years, respectively). In the pre-TCD group, 21 patients had overt stroke, three had other neurologic events, and two experienced indeterminate events. The post-TCD group had two patients who experienced overt stroke, six with other neurological events, and one who had an indeterminate event.

Daytime Steady-State Hemoglobin Saturation Is a Determinant of Cerebral Artery Blood Flow Velocity in Children With Sickle Cell Anemia [Abstract #1424]
Charles T. Quinn, MD, MS, The University of Texas Southwestern Medical Center, Dallas, TX

This study determined that low hemoglobin saturation (a decrease in the amount of oxygen in the blood) may predispose children with sickle cell disease to having a stroke by limiting oxygen delivery to the brain. Since hemoglobin saturation can be easily measured, it might be used along with transcranial Doppler ultrasonography (TCD) screening to better identify children with sickle cell disease at the highest risk for stroke.

The purpose of this study was to examine the relationship between daytime hemoglobin saturation and speed of blood flow in the brain measured by TCD, which indicates the risk of stroke, to determine whether lower hemoglobin saturation was associated with a higher TCD blood-flow speed and therefore a higher risk for stroke.

A retrospective analysis of the TCD measurements in 169 children (with an age range of 2-20 years and a mean of 8 years) with sickle cell disease from the Dallas Newborn Cohort was conducted. For each patient, analysis of the TCD blood-flow speeds in the main arteries of the brain, age at the time of TCD screening, and the most recent blood count and hemoglobin saturation were analyzed.

The study found that patients who had lower hemoglobin saturations had higher TCD blood-flow speeds, which means they had a higher risk of having a stroke. On average, the lower the hemoglobin saturation fell, the more the TCD blood-flow speed in the brain increased. Higher TCD blood-flow speeds increase the risk for stroke. The study concluded that the hemoglobin saturation, which can be painlessly measured by shining a light through the skin, is a new risk factor for stroke in children with sickle cell disease.

Prolonged Administration of Hydroxyurea Reduces Morbidity and Mortality in Adult Patients With Sickle Cell Syndromes: Long-Term Experience of a Single Center [Abstract #1445]
Ersi Voskaridou, MD, Laikon General Hospital, Athens, Greece

This single-center study found that the long-term administration of hydroxyurea in adult patients with sickle cell disease is safe and can improve survival and modify the prognosis of this disease. The beneficial effects of hydroxyurea suggest that doctors should consider expanding the use of hydroxyurea to all patients with sickle cell disease.

Hydroxyurea is commonly used for preventing painful sickle cell crises, reducing the frequency and length of hospital stays, and improving the quality of life of patients with sickle cell disease. However, determining whether hydroxyurea could also prevent severe chronic complications of the disease or improve survival in these patients had not yet been confirmed.

The purpose of this study was to evaluate the effects of hydroxyurea in a large number of patients who received the therapy over a long period of time. The medical records of 330 patients with sickle cell disease treated at the Thalassemia Center of Laikon Hospital in Athens, Greece, over the course of 20 years were retrospectively analyzed. Patients were divided into two groups: a total of 131 patients who received hydroxyurea treatment and 199 patients whose symptoms were addressed with conventional therapies. The typical dose of hydroxyurea given was 20 mg/kg/day, except for some patients where toxicity or lack of effectiveness required dose modifications of 15 to 35 mg/kg/day. All patients, except for rare exceptions, reported to the center every four to eight weeks for thorough laboratory work. The median follow-up was eight years for patients receiving hydroxyurea and five years for those who did not receive hydroxyurea.

The study found that the probability of 10-year survival was 91 percent for the patients treated with hydroxyurea compared with 70 percent for the conventionally treated patients. Additionally, patients receiving hydroxyurea showed a dramatic reduction of the frequency of severe painful crises (from 7.4?6.5 episodes per year pre-hydroxuyrea to 0.2?0.4 episodes post-hydroxyurea). A significant reduction in the number of red blood cell transfusions was also seen in patients treated with hydroxyurea (mean number of administered packed red cell units: 1.5?5.9 per year pre-hydroxyurea diminishing to almost zero during hydroxyurea treatment) as well as a significant reduction in hospital admissions (from 2.1?2.9 per year pre-hydroxyurea to 0.06?0.02 per year post-hydroxyurea).

Sickle cell disease results in many, often severe, complications affecting all organs due to vaso-occlusion (the blockage of small vessels by sickled cells). One of these severe complications is chest syndrome, which is often fatal. Hydroxyurea produced a significant reduction in the frequency of chest syndrome (from 6.1 percent pre-hydroxyurea to 0.8 percent during the hydroxyurea period). No significant difference was observed between the two treatments for the prevention or reduction of the frequency of avascular necrosis (blockage of small vessels in the bone area causing destruction to joints) or cerebrovascular episodes (blockage of small blood vessels in the brain).

Another characteristic feature of the disease is the presence of hemolytic crises (rapidly evolving anemia, jaundice, and fever), which further reduce hemoglobin levels and produces severe dysfunction in several organs. Patients treated with hydroxyurea had reduced hemolysis and improved total hemoglobin in comparison to the group of patients not treated with hydroxyurea. The difference observed in overall survival in patients who were given hydroxyurea is further magnified by the fact that that, prior to starting hydroxyurea, these patients had significantly higher transfusion requirements, frequency of painful crises, yearly number of admissions to the hospital, and increased intensity of hemolysis in comparison to patients who did not receive hydroxyurea.

Side effects of hydroxyurea therapy were minimal, predictable, and easily manageable. However, all patients were under close follow-up, with visits including thorough clinical and laboratory evaluation every two weeks for the first two months and then every four to eight weeks.


Screening with an ultrasound machine has proved highly successful in preventing stroke among children with sickle cell disease, by identifying children who are then preventively treated with blood transfusions. Over an eight-year period at The Children’s Hospital of Philadelphia, researchers found that the technique, transcranial Doppler ultrasonography (TCD), along with regular transfusions for children found

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Using a harmless virus to insert a corrective gene into mouse blood cells, scientists at St. Jude Children’s Research Hospital have alleviated sickle cell disease pathology. In their studies, the researchers found that the treated mice showed essentially no difference from normal mice. Although the scientists caution that applying the gene therapy to humans

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A unique approach to bone marrow transplantation pioneered in part by a Children’s Hospital of Pittsburgh of UPMC physician has proven to be the only safe and effective cure for sickle cell disease, according to a new study. Lakshmanan Krishnamurti, MD, a pediatric hematologist/oncologist at Children’s Hospital, helped pioneer a form of bone marrow transplantation

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A new study finds that youth populations with sickle cell disease (SCD) are receiving inadequate healthcare, and thus may fail to benefit from scientific advances. The study, published in Pediatric Blood & Cancer, finds that the patients, mostly African Americans, often lack insurance or access to specialized sickle cell centers for treatment. SCD, a blood

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