Experience of a Sickle Cell Screening Program in Baltimore Joseph M. Miller, MD, and Deborah C. Davis, BS Baltimore, Maryland
The hemoglobinopathies constitute a major medical problem in the black community of Baltimore. A sickle cell service should be designed to discover, educate, and, if necessary, treat. Screening is sound preventive medicine and may serve to introduce the patient to the concept of continuing medical surveillance. The prevention of serious complications in patients with the more severe types of hemoglobinopathy should be a basic goal in the program.
A sickle cell service, sponsored by public funds and in operation at this hospital for six years, has had as its purpose the discovery of individuals with hemoglobinopathies and the treatment of those patients requiring care. This report reviews what has transpired and offers suggestions for similar programs contemplated elsewhere. Traditionally, the medical response to the discovery of physical abnormality has been treatment and corrective action, if possible. In the absence of proven therapeutic measures, as in sickle cell disease, management consists of ameliorative procedures and advice in personal adjustment. Information about reproductive decisions is provided to individuals with the trait and the disease, to enhance their freedom of choice in this respect. Thus, discovery, education, and counseling are the keystones of the program.
Requests for reprints should be addressed to Joseph M. Miller, MD, Provident Hospital, Incorporated, 2600 Liberty Heights Avenue, Baltimore, MD 21215.
Details of Screening Potential screenees should be provided, before blood is drawn for testing, therefore, with a description of the disease, the carrier state, and the genetic implications of both. The testing process should be described so that the screenee knows what is being done, and that the tests may uncover some other abnormal variations of hemoglobin rather than those of sickle cell trait (HbAS) or sickle cell hemoglobin (HbSS). All consent must be voluntary and in writing. Each individual has the privilege of knowing the result of the test. These records are confidential in the true sense of the word. Results may not be released without the written consent of the screenee, parent, or guardian.
Target Population In general, the target population included: 1. Unmarried adolescents 2. Married young people 3. Babies 4. School children 5. Members of the Job Corps 6. Well-baby clinics
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
The hospital is located in an area composed predominantly of black people. In 39 census tracts in this area, the count in 1970 listed 204,734 blacks, comprising 90 percent of the population. Expected, then, was the observation that 96.5 percent of those screened were black and only 2.5 percent were "other races."
Methods Every individual screened had an electrophoresis on cellulose acetate. In those people with hemoglobin migrating in the area of the sickle cell band, a sodium dithionite solubility test was then done. If a hemoglobin C area were demonstrated, a citrate agar electrophoresis was done to determine whether or not hemoglobin C, E, or 0 were present. Further delineation of the C band was effected by a solubility test to differentiate between C and CHariem.
Results The hemoglobinopathies in this region mainly affect the black population, and so this review will be confined to blacks. In the total number of 39,510 blacks, all age groups were represented 839
Table 1. Age Groups of Screenees Age group Number Percent of total
0-6 5,000 12.65
7-14 13,834 35.01
15-34 16,854 42.65
45 and over 1,118 2.82
35-44 2,704 6.84
Table 2. Percentages of Screenees with Hemoglobinopathies
Type of Hemoglobin HbAS HbAC* HbAF** HbSS HbSC Others Totals
Number
Percentage of Screenees
3,100 993 52 36 59 96 4,336
7.85 2.51 0.13 0.09 0.15 0.24 10.97
* Hemoglobin C trait
**Hemoglobin A and fetal hemoglobin
Table 3. Percentage of Screenees with HbAS in Various Age Groups in Total Number Screened
Age Group
(years)
0-6 7-14 15-34 35-44 45 and over Totals
Number with HbAS
Number of Screenees
Percentage of Screenees
277 1,244 1,244 206 129 3,100
5,000 13,834 16,854 2,704 1,118 39,510
5.54 8.99 7.38 7.61 11.53 7.84
(Table 1), and the majority of these individuals (35,689 or 90 percent) were under age 34. Some type of hemoglobinopathy was found in 10.97 percent of the screenees (Table 2). A change in frequency in HbAS in the various age groups is demonstrated in Table 3. Except for a variation in the 7-14 year group, a decreasing incidence is apparent from the 45-year level and over at 11.53 percent to 5.54 percent at the 0-6-year age group. These numbers suggest that a dilution of the gene pool for HbAS is being witnessed. The frequency of HbAS in the different age groups was used as a challenge to support the contention that screening over the age of 35 is not necessary (Table 4). Under 35 years, 89.17 percent of the total abnormality was found, and these groups comprised 90.31 840
percent of those individuals screened. Retrospectively, because the trait is genetically determined and so fLxed, this parallelism could have been predicted and a lack of conformity would have occasioned surprise. Table 5 reinforces this observation and merely demonstrates that an increased incidence of the disease is found where a greater number of individuals are screened. Neel' writes that the frequency of classical sickle cell anemia prior to the action of selective mortality\should be approximately 2.7 per 1,000. In a population of slightly more than 20,000,000 blacks in this country, the expected number of cases would be 54,000. Because of the differential mortality, the actual number is perhaps one half to two thirds of this number. In the screening of the 39,510 blacks at this
hospital, the initial expected yield was 107 individuals with HbSS. Actually, only 36 patients (37 percent) of this nature were discovered. The disease evidently takes a marked toll from the moment of conception. According to Rucknagel,2sickle cell and C hemoglobin (HbSC) occurs in about one in 1,000 blacks. A similar frequency was found in this study.
Discussion and Recommendations Certain guidelines for future conduct may be gleaned from an examination of the results in this study. 1. Screening of "other races" should be discontinued. Only two individuals with an insignificant type of hemoglobinopathy were found in 1,329 individuals of "other races." 2. People over 35 years of age should not be examined, because men and women over that age usually do not wish to have children and genetic counseling is not necessary. The "stigma," ifsuch it be, or having the trait thereby remains undisclosed and the psychological harm of such knowledge upon this segment of the population is avoided. 3. Investigation of children up to age 15 should be most productive in results. If this group were thoroughly screened, all of the hemoglobinopathies would be discovered. These children are accessible in pediatric and well-baby clinics, nurseries, kindergartens, and elementary and secondary schools. Discovery of the variation at this time permits proper planning with the child and the family for the future. 4. Those individuals with hemoglobinopathies should have the opportunity to receive genetic counseling which entails a full examination of the disorder and its genetic potential. One-to-one conversation by physicians, nurses, and paramedical personnel, trained in this particular facet of medicine, should be provided in an impartial manner with consideration of alternative plans of action. Slides, films, and handouts are most useful as sources of educational information to reinforce the verbal discussion. The patient with sickle cell disease should have help to explore the multiple problems involved in education, marriage, and livelihood. Parents of such children should be fully informed about educational possibilities, physical activities, and eventual life profession. Sickle hemoglobin variations, because they affect 8-10 percent of the black
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
population, have received considerable attention and have created a state of emotional upset and fear in many parents and children. The concerns of parents and children must be met by a more humane approach by the medical profession. 5. Individuals with HbSS or HbSC, particularly women, need treatment for the duration of their lives. These diseases vary widely in severity, time of onset, frequency of crisis, functional status ofthe patient, and length of life. A service program which provides primary medical care and follow-up should be instituted on a regular outpatient basis to care for their total needs. Medication should be provided, even on a free basis, if necessary. Care should include the utilization of ancillary medical services for full support of the patient. Attention must be given to the reliefofpain during periods of crisis without making the patient a narcotic addict. 6. Careful correlation of the activities of the primary care Sickle Cell Clinic, the Emergency Room, and the hospital should be made. Sickle cell patients in remission should have regular appointments in primary care. If they have a crisis, they will usually go to the Emergency Room. Personnel in this area are frequently oriented toward trauma and general medical situations, and may not be versed in the intricacies of sickle cell disease therapy. These individuals may need direction about primary care and subsequent referral. If the patient is admitted to the hospital, outpatient information should be readily available to the attending
physician.
7. All primary care physicians and related paramedical personnel should be knowledgeable about trait and disease, the differences between them, how the diagnosis is made, and what treatment and counseling may offer. 8. Screening is sound preventive medicine and may serve to introduce the patient to the basic services offered by any good outpatient department. Prevention of serious complications must be a basic goal in any program involving sickle-cell disease. Construction of the program should be sound. It should include education; informed consent; proper environment; good outpatient services to which the patient may not only be referred for additional treatment but from which patients may be referred; and good feedback relationships to patient and doctor to obtain a
Table 4. Percentages of Screenees with HbAS in Various Age Groups Age Group
Number
Percentage of Total HbAs
277 1,244 1,244 206 129
8.93 40.12 40.12 6.64 4.16 99.97
0-6 7-14 15-34 35-44 45 and over Totals
3,100
Table 5. Parallelism of Incidence of HbAS with Total Number Screened
Age Group 0-6 7-14 15-34 35-44 45 and over
Totals
Number
Percentage of Screenees (Total, 39,510)
277 1,244 1,244 206 129 3,100
0.70 3.14 3.14 0.52 0.33 7.84
maximal therapeutic result. The care and treatment of patients with sickle cell disease is a minor hematologic specialty and perhaps should best be left to the interested and qualified pediatrician, internist, or hematologist.
Hazards of Screening Screening is good and worthwhile, but multiple hazards understandably exist when examination is contemplated. 1. A misconception about sickle cell trait exists among the laity and the profession. 2. Due to the necessary emphasis put upon the carrier state of HbAS and its relation to reproduction, a major effect upon the marriageability of a couple, each of whom is a carrier, may be raised. The risk of producing a child with HbSS exists in each pregnancy. Men and women with HbAS may be stigmatized and avoided, if the result is known. 3. Job discriminatio\n, limitation of access to some areas of potential livelihood, and problems with insurability may wrongly arise if the screenee is known to be a carrier. 4. Physical activities may be unnecessarily restricted in children who are carriers.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
Conclusions Education of the patient specifically and the public in general about HbAS and HbSS and their nuances is the proper justification for screening. Corporations and their medical services must be instructed about the general normalcy of the carrier state individual. The objections that the individual with HbAS is not better off by being aware of the abnormality and that a cost has been created by screening which does not produce a benefit for the patient are really not valid. Medical science must unravel the natural history of a disorder for which a treatment does not exist. At the same time, the individual must be protected from the psychological and social hazards which attend such. a program. A plan for sickle cell investigation is good only if public acceptance and benefits can be demonstrated, and if public education, counseling, and treatment of some kind are available. Literature Cited 1. Neel JV: Sickle cell disease: A worldwide problem. In Abramson H, Bertles JF, Wethefs DL (eds): Sickle Cell Disease: Diagnosis, Management, Education, and Research. St. Louis, CV Mosby, 1973 pp 55-70 2. Rusknagei DL: Genetic basis of sickle cell disease. In Abramson H, Bertles JF, Wethers DL (eds): Sickle Cell Disease: Diagnosis, Management, Education, and Research. St. Louis, CV Mosby, 1973, pp 55-70
841
The hemoglobinopathies constitute a major medical problem in the black community of Baltimore. A sickle cell service should be designed to discover, educate, and, if necessary, treat. Screening is sound preventive medicine and may serve to introduce the patient to the concept of continuing medical surveillance. The prevention of serious complications in patients with the more severe types of hemoglobinopathy should be a basic goal in the program.
A sickle cell service, sponsored by public funds and in operation at this hospital for six years, has had as its purpose the discovery of individuals with hemoglobinopathies and the treatment of those patients requiring care. This report reviews what has transpired and offers suggestions for similar programs contemplated elsewhere. Traditionally, the medical response to the discovery of physical abnormality has been treatment and corrective action, if possible. In the absence of proven therapeutic measures, as in sickle cell disease, management consists of ameliorative procedures and advice in personal adjustment. Information about reproductive decisions is provided to individuals with the trait and the disease, to enhance their freedom of choice in this respect. Thus, discovery, education, and counseling are the keystones of the program.
Requests for reprints should be addressed to Joseph M. Miller, MD, Provident Hospital, Incorporated, 2600 Liberty Heights Avenue, Baltimore, MD 21215.
Details of Screening Potential screenees should be provided, before blood is drawn for testing, therefore, with a description of the disease, the carrier state, and the genetic implications of both. The testing process should be described so that the screenee knows what is being done, and that the tests may uncover some other abnormal variations of hemoglobin rather than those of sickle cell trait (HbAS) or sickle cell hemoglobin (HbSS). All consent must be voluntary and in writing. Each individual has the privilege of knowing the result of the test. These records are confidential in the true sense of the word. Results may not be released without the written consent of the screenee, parent, or guardian.
Target Population In general, the target population included: 1. Unmarried adolescents 2. Married young people 3. Babies 4. School children 5. Members of the Job Corps 6. Well-baby clinics
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
The hospital is located in an area composed predominantly of black people. In 39 census tracts in this area, the count in 1970 listed 204,734 blacks, comprising 90 percent of the population. Expected, then, was the observation that 96.5 percent of those screened were black and only 2.5 percent were "other races."
Methods Every individual screened had an electrophoresis on cellulose acetate. In those people with hemoglobin migrating in the area of the sickle cell band, a sodium dithionite solubility test was then done. If a hemoglobin C area were demonstrated, a citrate agar electrophoresis was done to determine whether or not hemoglobin C, E, or 0 were present. Further delineation of the C band was effected by a solubility test to differentiate between C and CHariem.
Results The hemoglobinopathies in this region mainly affect the black population, and so this review will be confined to blacks. In the total number of 39,510 blacks, all age groups were represented 839
Table 1. Age Groups of Screenees Age group Number Percent of total
0-6 5,000 12.65
7-14 13,834 35.01
15-34 16,854 42.65
45 and over 1,118 2.82
35-44 2,704 6.84
Table 2. Percentages of Screenees with Hemoglobinopathies
Type of Hemoglobin HbAS HbAC* HbAF** HbSS HbSC Others Totals
Number
Percentage of Screenees
3,100 993 52 36 59 96 4,336
7.85 2.51 0.13 0.09 0.15 0.24 10.97
* Hemoglobin C trait
**Hemoglobin A and fetal hemoglobin
Table 3. Percentage of Screenees with HbAS in Various Age Groups in Total Number Screened
Age Group
(years)
0-6 7-14 15-34 35-44 45 and over Totals
Number with HbAS
Number of Screenees
Percentage of Screenees
277 1,244 1,244 206 129 3,100
5,000 13,834 16,854 2,704 1,118 39,510
5.54 8.99 7.38 7.61 11.53 7.84
(Table 1), and the majority of these individuals (35,689 or 90 percent) were under age 34. Some type of hemoglobinopathy was found in 10.97 percent of the screenees (Table 2). A change in frequency in HbAS in the various age groups is demonstrated in Table 3. Except for a variation in the 7-14 year group, a decreasing incidence is apparent from the 45-year level and over at 11.53 percent to 5.54 percent at the 0-6-year age group. These numbers suggest that a dilution of the gene pool for HbAS is being witnessed. The frequency of HbAS in the different age groups was used as a challenge to support the contention that screening over the age of 35 is not necessary (Table 4). Under 35 years, 89.17 percent of the total abnormality was found, and these groups comprised 90.31 840
percent of those individuals screened. Retrospectively, because the trait is genetically determined and so fLxed, this parallelism could have been predicted and a lack of conformity would have occasioned surprise. Table 5 reinforces this observation and merely demonstrates that an increased incidence of the disease is found where a greater number of individuals are screened. Neel' writes that the frequency of classical sickle cell anemia prior to the action of selective mortality\should be approximately 2.7 per 1,000. In a population of slightly more than 20,000,000 blacks in this country, the expected number of cases would be 54,000. Because of the differential mortality, the actual number is perhaps one half to two thirds of this number. In the screening of the 39,510 blacks at this
hospital, the initial expected yield was 107 individuals with HbSS. Actually, only 36 patients (37 percent) of this nature were discovered. The disease evidently takes a marked toll from the moment of conception. According to Rucknagel,2sickle cell and C hemoglobin (HbSC) occurs in about one in 1,000 blacks. A similar frequency was found in this study.
Discussion and Recommendations Certain guidelines for future conduct may be gleaned from an examination of the results in this study. 1. Screening of "other races" should be discontinued. Only two individuals with an insignificant type of hemoglobinopathy were found in 1,329 individuals of "other races." 2. People over 35 years of age should not be examined, because men and women over that age usually do not wish to have children and genetic counseling is not necessary. The "stigma," ifsuch it be, or having the trait thereby remains undisclosed and the psychological harm of such knowledge upon this segment of the population is avoided. 3. Investigation of children up to age 15 should be most productive in results. If this group were thoroughly screened, all of the hemoglobinopathies would be discovered. These children are accessible in pediatric and well-baby clinics, nurseries, kindergartens, and elementary and secondary schools. Discovery of the variation at this time permits proper planning with the child and the family for the future. 4. Those individuals with hemoglobinopathies should have the opportunity to receive genetic counseling which entails a full examination of the disorder and its genetic potential. One-to-one conversation by physicians, nurses, and paramedical personnel, trained in this particular facet of medicine, should be provided in an impartial manner with consideration of alternative plans of action. Slides, films, and handouts are most useful as sources of educational information to reinforce the verbal discussion. The patient with sickle cell disease should have help to explore the multiple problems involved in education, marriage, and livelihood. Parents of such children should be fully informed about educational possibilities, physical activities, and eventual life profession. Sickle hemoglobin variations, because they affect 8-10 percent of the black
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
population, have received considerable attention and have created a state of emotional upset and fear in many parents and children. The concerns of parents and children must be met by a more humane approach by the medical profession. 5. Individuals with HbSS or HbSC, particularly women, need treatment for the duration of their lives. These diseases vary widely in severity, time of onset, frequency of crisis, functional status ofthe patient, and length of life. A service program which provides primary medical care and follow-up should be instituted on a regular outpatient basis to care for their total needs. Medication should be provided, even on a free basis, if necessary. Care should include the utilization of ancillary medical services for full support of the patient. Attention must be given to the reliefofpain during periods of crisis without making the patient a narcotic addict. 6. Careful correlation of the activities of the primary care Sickle Cell Clinic, the Emergency Room, and the hospital should be made. Sickle cell patients in remission should have regular appointments in primary care. If they have a crisis, they will usually go to the Emergency Room. Personnel in this area are frequently oriented toward trauma and general medical situations, and may not be versed in the intricacies of sickle cell disease therapy. These individuals may need direction about primary care and subsequent referral. If the patient is admitted to the hospital, outpatient information should be readily available to the attending
physician.
7. All primary care physicians and related paramedical personnel should be knowledgeable about trait and disease, the differences between them, how the diagnosis is made, and what treatment and counseling may offer. 8. Screening is sound preventive medicine and may serve to introduce the patient to the basic services offered by any good outpatient department. Prevention of serious complications must be a basic goal in any program involving sickle-cell disease. Construction of the program should be sound. It should include education; informed consent; proper environment; good outpatient services to which the patient may not only be referred for additional treatment but from which patients may be referred; and good feedback relationships to patient and doctor to obtain a
Table 4. Percentages of Screenees with HbAS in Various Age Groups Age Group
Number
Percentage of Total HbAs
277 1,244 1,244 206 129
8.93 40.12 40.12 6.64 4.16 99.97
0-6 7-14 15-34 35-44 45 and over Totals
3,100
Table 5. Parallelism of Incidence of HbAS with Total Number Screened
Age Group 0-6 7-14 15-34 35-44 45 and over
Totals
Number
Percentage of Screenees (Total, 39,510)
277 1,244 1,244 206 129 3,100
0.70 3.14 3.14 0.52 0.33 7.84
maximal therapeutic result. The care and treatment of patients with sickle cell disease is a minor hematologic specialty and perhaps should best be left to the interested and qualified pediatrician, internist, or hematologist.
Hazards of Screening Screening is good and worthwhile, but multiple hazards understandably exist when examination is contemplated. 1. A misconception about sickle cell trait exists among the laity and the profession. 2. Due to the necessary emphasis put upon the carrier state of HbAS and its relation to reproduction, a major effect upon the marriageability of a couple, each of whom is a carrier, may be raised. The risk of producing a child with HbSS exists in each pregnancy. Men and women with HbAS may be stigmatized and avoided, if the result is known. 3. Job discriminatio\n, limitation of access to some areas of potential livelihood, and problems with insurability may wrongly arise if the screenee is known to be a carrier. 4. Physical activities may be unnecessarily restricted in children who are carriers.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 71, NO. 9, 1979
Conclusions Education of the patient specifically and the public in general about HbAS and HbSS and their nuances is the proper justification for screening. Corporations and their medical services must be instructed about the general normalcy of the carrier state individual. The objections that the individual with HbAS is not better off by being aware of the abnormality and that a cost has been created by screening which does not produce a benefit for the patient are really not valid. Medical science must unravel the natural history of a disorder for which a treatment does not exist. At the same time, the individual must be protected from the psychological and social hazards which attend such. a program. A plan for sickle cell investigation is good only if public acceptance and benefits can be demonstrated, and if public education, counseling, and treatment of some kind are available. Literature Cited 1. Neel JV: Sickle cell disease: A worldwide problem. In Abramson H, Bertles JF, Wethefs DL (eds): Sickle Cell Disease: Diagnosis, Management, Education, and Research. St. Louis, CV Mosby, 1973 pp 55-70 2. Rusknagei DL: Genetic basis of sickle cell disease. In Abramson H, Bertles JF, Wethers DL (eds): Sickle Cell Disease: Diagnosis, Management, Education, and Research. St. Louis, CV Mosby, 1973, pp 55-70
841
