Silent infarction as a risk factor for overt stroke in children with sickle cell anemia: a report from the Cooperative Study of Sickle Cell Disease.

Objective: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke.

Methods: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain MRI at age 6 years or older, and (3) had no overt stroke before a first MRI. MRI results and clinical and laboratory parameters were tested as predictors of stroke.

Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment.

Treatment advances over the past 25 years have significantly decreased morbidity and mortality in children with sickle cell disease. Aggressive management of fever, early diagnosis of acute chest syndrome, judicious use of transfusions and proper treatment of pain can improve quality of life and prognosis for these children. Prophylactic hydroxyurea therapy has been shown to reduce the incidence and severity of pain crises in adults with sickle cell disease and has been effective in limited studies conducted in children.

Sickle cell disease in childhood: Part I. Laboratory diagnosis, pathophysiology and health maintenance.

Over the past 25 years, morbidity and mortality have decreased significantly in children with sickle cell disease, and screening tests are now available to diagnose the disease in newborns. The incidence of sepsis caused by pneumococcal and Haemophilus influenzae infections has declined because of the prophylactic administration of penicillin soon after birth and the timely administration of pneumococcal and H. influenzae type b vaccines.

Prediction of adverse outcomes in children with sickle cell disease.

Background: The ability to identify infants with sickle cell anemia who are likely to have severe complications later in life would permit accurate prognostication and tailoring of therapy to match disease-related risks and facilitate planning of clinical trials. We attempted to define the features of such babies by following the clinical course of 392 children with sickle cell disease from infancy to about the age of 10 years.

Methods: We analyzed the records of 392 infants who received the diagnosis of homozygous sickle cell anemia or sickle cell-Beta(0)-thalassemia before the age of six months and for whom comprehensive clinical and laboratory data were recorded prospectively; data were available for a mean (+/-SD) of 10.

Silent cerebral infarcts in sickle cell anemia: a risk factor analysis. The Cooperative Study of Sickle Cell Disease.

Background: Silent infarcts have been reported in 17% of young patients with sickle cell disease and are associated with impaired performance on standardized psychometric tests. Risk factors for the development of these lesions have not been identified.

Methods: Investigators in the Cooperative Study of Sickle Cell Disease performed a brain magnetic resonance imaging scan on sickle cell anemia patients age 5.

Cerebrovascular accidents in sickle cell disease: rates and risk factors.

Cerebrovascular accident (CVA) is a major complication of sickle cell disease. The incidence and mortality of and risk factors for CVA in sickle cell disease patients in the United States have been reported only in small patient samples. The Cooperative Study of Sickle Cell Disease collected clinical data on 4,082 sickle cell disease patients enrolled from 1978 to 1988.

Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis.

Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years in children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses.

Study Design: Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebo treatment. These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization.

Functional asplenia in hemoglobin SC disease.

The incidence of functional asplenia in sickle-hemoglobin C (SC) disease has not been defined, and the use of prophylactic penicillin to prevent life-threatening septicemia in this disorder is controversial. The percentage of red blood cells with pits (pit count) is a reliable assay of splenic function in other disorders but has not been validated in hemoglobin SC disease. To address these issues, we conducted a prospective, multicenter study of splenic function in persons with hemoglobin SC disease.

Accelerated healing of chronic sickle-cell leg ulcers treated with RGD peptide matrix. RGD Study Group.

Leg ulcers are a chronic manifestation of sickle-cell disease (SCD) and are often painful, disabling, and difficult to treat. RGD peptide matrix treatment is a novel therapy designed to provide a topical synthetic extracellular matrix that can act as a temporary substitute for the damaged natural matrix at the ulcer site. In this randomized, placebo-controlled, double-blind, prospective, multicenter investigation, SCD patients with full-thickness leg ulcers were treated with standard therapy plus RGD peptide matrix or saline placebo once weekly for up to 10 weeks.

Laboratory profile of sickle cell disease: a cross-sectional analysis. The Cooperative Study of Sickle Cell Disease.

We have collected steady-state laboratory data for over 2600 patients, age 2 years and over, with sickle cell anemia (HbSS), HbSC disease, and HbS-beta(+)-thalassemia. The packed cell volume (PCV) is lower in males than in females until 17 or 18 years of age in HbSS and ages 13 to 15 in HbSC, but then becomes consistently higher in males. After age 40, the PCV falls in HbSS.

Febrile episodes in children with sickle cell disease treated on an ambulatory basis.

Children with sickle cell disease have a greatly increased potential for developing rapid and at times fatal sepsis from Streptococcus pneumoniae. Hospitalization and parenteral antibiotic treatment in all febrile children with sickle cell disease have thus become the standard of care at most sickle cell centers. As an alternative approach, we managed selected febrile children with sickle cell disease on an ambulatory basis with parenteral ceftriaxone to determine its safety and effectiveness in preventing sepsis and reducing the number of days of hospitalization.

Management of acute splenic sequestration crisis in sickle cell disease.

Acute splenic sequestration crisis (ASSC) is a significant cause of early morbidity in children with sickle cell disease. With timely diagnosis and prompt transfusion, the outcome is good. However, recurrences are frequent, and both splenectomy and long-term transfusion therapy have been advanced as appropriate preventive approaches.

Spleen dysfunction in hemoglobinopathies determined by pitted red cells.

Splenic dysfunction measured by pitted red cells (pit) was studied in hemoglobinopathies (SS-, SC-, and S beta-type thalassemias and CC-type hemoglobinopathy) in relation to age, in steady state, and during certain significant events. Our experience revealed that the pit count rose with age during steady state in most children with SS disease. A marked increase in pit count was noted in patients with CC disease.

Reversibility of splenic function by transfusion in two young adults with sickle cell anemia.

A level of circulating "pitted" or vesiculated red blood cells higher than 3.5% was recently reported in studies in the Cooperative Study of Sickle Cell Disease to correlate with splenic dysfunction as shown by spleen scans. Reversal of splenic dysfunction by transfusion in children with sickle cell anemia (SS disease) is known to occur in the young child.

Growth hormone response to growth hormone releasing factor in sickle cell disease.

Many children with sickle cell disease (SCD) have impaired growth during childhood and adolescence, with patterns of growth consistent with constitutional delay in growth and pubertal development (CDGD). We evaluated the growth hormone (GH) response to a rapid intravenous (i.v.

Newborn screening for hemoglobinopathies: the benefit beyond the target.

As a result of New York State's Newborn Screening Program 4,565 neonates with trait hemoglobinopathies were identified and 3,200 families were notified of the results of testing their infants in New York City in 1982. Of the 1,531 families (2,190 parents) tested and counseled, 22 parents were diagnosed with sickle cell disease and 39 couples were found to be at-risk for having a child with sickle cell disease. Amniocentesis was performed in 14 of the 28 at-risk pregnant women and three of the four affected pregnancies were terminated.

Bacteremia in sickle hemoglobinopathies.

We analyzed 178 episodes of bacteremia that occurred during 13,771 patient-years of follow-up of 3451 patients with sickle hemoglobinopathies. Age-specific incidence rates of bacteremia were calculated for patients with sickle cell anemia (SS) and sickle cell-hemoglobin C (SC) disease. The incidence rate was highest among children with SS and SC younger than age 2 years.

Pitfalls in diagnosis of osteomyelitis in children with sickle cell disease.

The cases of three children with unusual features of osteomyelitis and sickle cell disease are presented. Two children had salmonella osteomyelitis, one with a recurrence 1.5 years after adequate intravenous therapy.

Current sickle cell screening program for newborns in New York City, 1979-1980.

The newborn screening program mandated by the New York State Public Health Law requires that every baby born in the state be tested for eight conditions including sickle cell anemia. Although sickle cell screening of newborns has been in operation since 1975, the follow-up program for case retrieval to obtain repeat blood samples for definitive diagnosis and referral of diagnosed patients for ongoing medical care was established only in 1979. Of the 106,565 blood samples tested in New York City Newborn Screening Laboratory, March 1, 1979 to February 29, 1980, 141 infants were identified on repeat blood testing as having various forms of sickle cell disease (SS, SC and S beta-Thalassemia) and were referred for ongoing medical care.

Problems and complications in the adolescent with sickle cell disease.

The period of adolescence in the patient with sickle cell disease seems to be a period of relative calm, medically speaking. The current 5-year prospective Cooperative Study of the Clinical Course of Sickle Cell Disease should demonstrate the actual spectrum of disease in this age group. The recent literature documents with significant relationship between retardation of growth and sexual maturation in the child with sickle cell disease, an effect which seems independent of the severity of the disease.

Evaluation of the expanded newborn screening program in New York City.

Since September 1974, New York State public health law has mandated that all newborn infants be tested for phenylketonuria, maple syrup urine disease, homocystinuria, histidinemia, galactosemia, adenosine deaminase deficiency, and sickle cell anemia in accordance with regulations of the state commissioner of health. During the period from May 1, 1975, to April 30, 1976, a total of 110,180 babies born in New York City were tested for these seven conditions. One year's experience with the screening program demonstrated a paucity of technological problems, low observed rate of both false-negatives and -positives, and the expected incidence of the conditions of highest prevalence, incidentally found during screening: i.