Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group.

BACKGROUND: The acute chest syndrome is the leading cause of death among patients with sickle cell disease. Since its cause is largely unknown, therapy is supportive. Pilot studies with improved diagnostic techniques suggest that infection and fat embolism are underdiagnosed in patients with the syndrome. METHODS: In a 30-center study, we analyzed 671 episodes of the acute chest syndrome in 538 patients with sickle cell disease to determine the cause, outcome, and response to therapy. We evaluated a treatment protocol that included matched transfusions, bronchodilators, and bronchoscopy. Samples of blood and respiratory tract secretions were sent to central laboratories for antibody testing, culture, DNA testing, and histopathological analyses. RESULTS: Nearly half the patients were initially admitted for another reason, mainly pain. When the acute chest syndrome was diagnosed, patients had hypoxia, decreasing hemoglobin values, and progressive multilobar pneumonia. The mean length of hospitalization was 10.5 days. Thirteen percent of patients required mechanical ventilation, and 3 percent died. Patients who were 20 or more years of age had a more severe course than those who were younger. Neurologic events occurred in 11 percent of patients, among whom 46 percent had respiratory failure. Treatment with phenotypically matched transfusions improved oxygenation, with a 1 percent rate of alloimmunization. One fifth of the patients who were treated with bronchodilators had clinical improvement. Eighty-one percent of patients who required mechanical ventilation recovered. A specific cause of the acute chest syndrome was identified in 38 percent of all episodes and 70 percent of episodes with complete data. Among the specific causes were pulmonary fat embolism and 27 different infectious pathogens. Eighteen patients died, and the most common causes of death were pulmonary emboli and infectious bronchopneumonia. Infection was a contributing factor in 56 percent of the deaths. CONCLUSIONS: Among patients with sickle cell disease, the acute chest syndrome is commonly precipitated by fat embolism and infection, especially community-acquired pneumonia. Among older patients and those with neurologic symptoms, the syndrome often progresses to respiratory failure. Treatment with transfusions and bronchodilators improves oxygenation, and with aggressive treatment, most patients who have respiratory failure recover.

Surgery in patients with hemoglobin SC disease. Preoperative Transfusion in Sickle Cell Disease Study Group.

While surgery is commonly required for complications related to hemoglobin SC (HbSC) disease, little is known about the perioperative complications or the indications for preoperative transfusion in this group. We describe the patient characteristics, preoperative transfusion regimens, and outcome in 92 patients with HbSC and sickle-variants undergoing elective surgery. Thirty-eight percent of the patients were transfused preoperatively. Patients transfused were more likely to have been hospitalized in the year prior to the surgery and scheduled for abdominal procedures. Abdominal and ear, nose and throat procedures were the most common surgeries in our study. The overall complication rate was 18% and sickle cell-related complications occurred in 9% of patients. In patients undergoing intra-abdominal procedures, the incidence of sickle cell-related complications was significantly higher in those patients not transfused prior to their surgery (35 vs. 0%). There were two deaths. We recommend selective use of preoperative transfusion in patients with HbSC disease undergoing surgery. Transfusion appears to be beneficial in abdominal cases but is not necessary with minor procedures such as myringtomy.

Chronic hepatitis C in patients with sickle cell disease.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibody in patients with sickle cell disease and to analyze the nature of chronic liver disease in these patients. METHODS: A total of 99 patients attending a comprehensive sickle cell and thalassemia program at the Interfaith Medical Center, Brooklyn, NY, participated in the study. Eighty-five patients had sickle cell anemia (ss), eight had sickle C disease (sc), and six had sickle B thalassemia. History of blood transfusion, i.v. drug use, homosexuality, and alcohol abuse was obtained with a questionnaire and chart review. All patients were screened for HCV antibody by a first generation enzyme-linked immunosorbent assay. All positive results were confirmed with radioimmunoblot assay II (RIBA II). Patients were also checked for the presence of hepatitis B surface antigen. ALT levels were measured, and percutaneous liver biopsies were performed in patients positive for HCV antibody and greater than 1.5 times the normal ALT levels. RESULTS: Antibody to HCV was detected in 10/99 patients (10.10%). Seven of 30 patients (23.33%) who received more than 10 U of packed red blood cells were positive for HCV antibody. Only 3/38 (7.9%) patients with less than 10 U of packed red blood cells in the past were positive for HCV antibody. None of the patients who never received blood transfusion were positive for HCV antibody (0/31 or 0%). A total of seven liver biopsies were performed in patients positive for HCV antibody. Two out of seven specimens (28.57%) showed significant liver damage. One revealed cirrhosis, and the other showed chronic active hepatitis. The remainder of liver biopsies (5/7; 71.42%) showed only mild portal inflammation. CONCLUSIONS: The prevalence of HCV antibody is directly related to the number of blood transfusions in patients with sickle cell disease. Chronic HCV infection could be a major cause of cirrhosis of the liver in these patients.

Pregnancy in sickle cell disease: experience of the Cooperative Study of Sickle Cell Disease.

OBJECTIVE: To determine the maternal and fetal outcomes of pregnancy in women with sickle cell disease. METHODS: The subjects were part of a cohort recruited from 19 centers for a prospective study of the clinical course of sickle cell disease. Each participant was evaluated using a structured protocol in which steady-state data and information on both sickle- and non-sickle-related events were collected. The rates of antepartum and intrapartum complications were tallied for pregnancies carried to delivery. Fetal outcome was assessed according to gestational age, birth weight, and Apgar score. Differences among genotypes in event rates were assessed using Fisher exact test. Differences in gestational age and birth weight, and predictors of these outcomes, were assessed using analyses of covariance. RESULTS: Two hundred eighty-six of the 445 reported pregnancies proceeded to delivery. Non-sickle-related antepartum and intrapartum complication rates were comparable with those of African-American women who did not have sickle cell disease. One of the two deaths observed during this study was directly related to the presence of sickle cell disease. Rates of maternal morbidity from sickle cell disease were the same during pregnancy as during the nonpregnant state. Ninety-nine percent of those pregnancies carried to delivery resulted in a live birth. Twenty-one percent of the infants born to women of the SS genotype were small for gestational age (SGA). Preeclampsia and acute anemic events were identified as risk factors for SGA infants. CONCLUSIONS: Those caring for women with sickle cell disease should support them if they desire to have children.

Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease.

Within the Cooperative Study of Sickle Cell Disease, 694 infants with confirmed sickle cell disease were enrolled at less than 6 months of age. Information about the nature and frequency of complications was collected prospectively over a 10-year period. Painful crises and acute chest syndrome were the most common sickle cell-related events in homozygous sickle cell anemia (SS), hemoglobin SC disease (SC), and S beta thalassemia patients (overall incidence in SS patients of 32.4 and 24.5 cases per 100 person-years, respectively). Bacteremia occurred most frequently in SS children under 4 years of age and in SC patients less than 2 years of age. The mortality rate was low in this cohort compared with that found in previous reports. Twenty children, all with Hb SS, died (1.1 deaths per 100 person-years among SS patients). Infection, most commonly with Streptococcus pneumoniae and Hemophilus influenzae, caused 11 deaths. Two children died of splenic sequestration, 1 of cerebrovascular accident, and 6 of unclear causes. Two patients underwent cholecystectomies, and 17 underwent splenectomies after one or more splenic sequestration crises. The experience of this cohort should reflect closely the true clinical course of those children with Hb SS and Hb SC disease who are observed in sickle cell centers in the United States.

Osteonecrosis of the humeral head in sickle cell disease.

The prevalence and incidence of osteonecrosis (ON) of the humeral head in sickle cell disease was determined by a study of 2524 patients who were entered into a prospective study and followed for an average of 5.6 years. At entry, 5.6% had roentgenographic evidence of ON in one or both shoulders. There was little difference in age-adjusted prevalence among genotypes, but there were striking differences in age-specific rates. Observed at ages ranging from five to 24 years, 3.25% of sickle cell anemia (S/S) patients, but only 1.1% of sickle cell disease (S/C) patients, had ON. No S/beta+ thalassemia patients younger than 25 years of age had ON on entry. The highest age-adjusted incidence rate was found in S/S patients with concomitant alpha-thalassemia (4.85 per hundred patient-years), followed by S/beta zero-thalassemia (4.84 per hundred patient-years), S/beta+ thalassemia (2.61 per hundred patient-years), S/S without alpha-thalassemia (2.54 per hundred patient-years), and S/C (1.66 per hundred patient-years). Only 20.9% of patients reported pain or had limited range of movement at the time of diagnosis. Sickle cell disease is a frequent cause of ON of the humeral head, especially in children and young adults.

Sickle cell disease as a cause of osteonecrosis of the femoral head.

BACKGROUND AND METHODS: Osteonecrosis of the femoral head is an important complication of sickle cell disease. We studied 2590 patients who were over 5 years of age at entry and followed them for an average of 5.6 years. Patients were examined twice a year, and radiographs of the hips were taken at least twice: at study entry and approximately three years later. RESULTS: At study entry, 9.8 percent of patients were found to have osteonecrosis of one or both femoral heads. On follow-up, patients with the hemoglobin SS genotype and alpha-thalassemia were at the greatest risk for osteonecrosis (age-adjusted incidence rate, 4.5 cases per 100 patient-years, as compared with 2.4 in patients with the hemoglobin SS genotype without alpha-thalassemia and 1.9 in those with the hemoglobin SC genotype). Although the rate of osteonecrosis in patients with the hemoglobin SC genotype did not differ significantly from that in patients with the hemoglobin SS genotype without alpha-thalassemia, osteonecrosis tended to develop in these patients later in life. Intermediate rates of osteonecrosis were observed among patients with the hemoglobin S-beta zero-thalassemia and the hemoglobin S-beta(+)-thalassemia genotypes (3.6 and 3.3 cases per 100 patient-years, respectively). Osteonecrosis was found in patients as young as five years old (1.8 cases per 100 patient-years for all genotypes). The frequency of painful crises and the hematocrit were positively associated with osteonecrosis. The mean corpuscular volume and serum aspartate aminotransferase level were negatively associated. Twenty-seven patients had hip arthroplasty during the study; 10 were under 25 years of age. Five of the 27 required reoperation 11 to 53 months after the initial operation. CONCLUSIONS: Osteonecrosis of the femoral head is common in patients with sickle cell disease, with an incidence ranging from about 2 to 4.5 cases per 100 patient-years. Patients with the hemoglobin SS genotype and alpha-thalassemia and those with frequent painful crises are at highest risk. The overall prevalence is about 10 percent. The results of hip arthroplasty are poor.

Thrombotic thrombocytopenic purpura in patients with the acquired immunodeficiency syndrome (AIDS)-related complex. A report of two cases.

Immune thrombocytopenia has been reported with increased incidence in high-risk persons such as intravenous drug addicts and homosexual men who have serologic evidence of infection with human immunodeficiency virus (HIV). Thrombotic thrombocytopenic purpura, generally regarded as a rare disorder, has also been seen in association with exposure to HIV. Two patients had classical symptoms and laboratory findings of thrombotic thrombocytopenic purpura and the acquired immunodeficiency syndrome (AIDS)-related complex. Both patients belong to high-risk groups. They were treated with conventional therapy for thrombotic thrombocytopenic purpura and followed for 3 months. Their response to treatment was no different from that of other groups of patients with this syndrome. This article alerts physicians to the possible association of thrombotic thrombocytopenic purpura, AIDS, and AIDS-related complex.

Recruitment in the Cooperative Study of Sickle Cell Disease (CSSCD).

The Cooperative Study of Sickle Cell Disease (CSSCD) is a multiinstitutional investigation of the natural history of clinical course of sickle cell disease from birth through adulthood. The study is not a trial; rather, it involves data collection at 23 institutions in a uniform, standardized fashion on 3800 patients. Recruitment aspects that were addressed include issues related to recruitment of different age groups, ranging from newborns to pregnant women to patients over 50 years of age; the need to include mildly affected patients to ensure that the study would not reflect only a severe hospital-based population; recruitment from rural populations; and the need to screen and enter a newborn population at birth. The recruitment goal of entering 3200 patients, including 2100 patients with SS hemoglobinopathy, over a 24-month period was accomplished after 27 months.

Interaction of chromosomes bearing 1, 2 or 3 alpha-globin genes in an American black family with alpha-thalassemia.

Utilizing restriction endonuclease mapping and molecular hybridization we have determined the number and arrangement of the alpha-globin genes in members of an American Black family in which alpha-thalassemia is present. In addition to chromosomes bearing 0, 1 or 2 alpha-genes, an unusual chromosome bearing 3 alpha-globin genes was detected in 3 family members. In 2 family members the 3 alpha-globin gene chromosome was present opposite a chromosome containing a single alpha-globin gene; these cases represent the first reports of the alpha alpha alpha/-alpha genotype. The presence of the stigmata of "mild" alpha-thalassemia trait in one of these subjects indicates that the 3 alpha-gene chromosome probably does not direct the synthesis of significantly more alpha-globin chains than does the 2 alpha-gene chromosome.

Alpha thalassaemia in American blacks: a study of a family with five cases of haemoglobin H disease.

Five cases of HbH disease were discovered in a large family of American Blacks. Anaemia was mild with PCV ranging from 0.275 to 0.405. The amount of HbH was 2--6%. Studies of haemoglobin synthesis in peripheral blood reticulocytes demonstrated marked deficits in alpha globin production with an average alpha/beta ratio of 0.31 (range 0.22--0.36). Eighteen additional family members had evidence of thalassaemia trait and were provisionally classified as either alpha-thal-1 (average MCV 65.2 fl; range 59--70) or alpha-thal-2 (average MCV 79.6 fl; range 74--88). A subject with altha-thal-1 trait had an alpha/beta ratio of 0.56; the average for five cases of alpha-thal-2 was 0.73. One other family member was thought to be homozygous for alpha-thal-2 trait and exhibited an MCV of 65 fl with an alpha/beta ratio of 0.5. These data reconfirm that in Blacks with alpha thalassaemia the proportion of HbH is lower and the severity of anaemia is less than in certain other racial groups, e.g. Southeast Asians. However, the degree of hypochromia and microcytosis and the imbalance in alpha and beta globin synthesis appear to be similar in Blacks and other races. These results suggest that the milder clinical course of HbH disease in Blacks is not a result of greater alpha globin production in that population of thalassaemics.

Pseudohyperkalemia and extreme leukocytosis.

Two patients with chronic lymphocytic leukemia and pseudolhyperkalemia are described. Both patients had white blood cell counts exceeding 600,000 per cubic millimeter. Routine determinations of serum potassium were elevated while normal values were obtained when plasma and serum were separated within 30 minutes of venipuncture. Incubation of clotted and heparinized specimens for 6 hours was accompanied by a marked increase of potassium levels. This study indicates that extreme leukocytosis alone can give rise to apparent hyperkalemiamtrue values can be obtained if the determinations are performed quickly after venipuncture.