revised April 14, 1999
Outpatient Management Issues in Sickle Cell Disease
Sickle cell disease results from an amino acid substitution of valine for glutamic acid at position 6 of the beta-globin chain. This alteration causes deoxygenated sickle hemoglobin to form polymers that ultimately destroy red cells, thereby producing anemia. If sickle cell disease only produced anemia, the problem would be relatively minor, as people can tolerate the typical hemoglobin levels of 7 or 8 g/dl reasonably well. The key difficulty with sickle cell disease is the damage to tissues and organs produced when deformed sickle erythrocytes occlude the microcirculation. The variegate manifestations of sickle cell disease are due ultimately to this problem.
The routine care of people with sickle cell disease does not necessarily require a hematologist. With few exceptions, the common complications are familiar to the experienced internist. The key to care of patients with sickle cell disease is knowing which problems are likely to result from the condition, and preventing these complications where possible. This means creating a program of regular follow-up in the office, rather than intervening when crises develop. The momentum in medical care has swung away from medical subspecialists and toward primary care physicians. Physicians trained in general medicine will play an increasingly important role in the management of patients with sickle cell disease.
The care of patients with sickle cell disease does require the expertise of medical subspecialists at times. Episodes of acute chest syndrome or splenic sequestration crisis are best handled by hematologists who are familiar with these complications. Sickle cell disease also requires coordination with other medical specialists, such as ophthalmologists. In this sense, the disease is no different from any other chronic medical illness, such as diabetes or hypertension. Health monitoring and prevention of complications are key. Health maintenance, which has become a shibboleth in many discussions of medical care, can truly be achieved for patients with sickle cell disease. Further, the savings to society in avoiding lost productivity and unnecessary medical expense is significant. More significant is avoiding unnecessary suffering by our fellow human beings.
Transition between Pediatric and Adult Care
As recently as the 1960's, sickle cell disease was considered a issue of childhood care, since relatively few patients survived very far into adulthood. No cure for the disorders has been developed. However, improvements in general medical care and the development of palliative treatments have extended life expectancy well into adulthood for these patients. The general medical services of most adult hospitals lack comprehensive care programs for patients with sickle cell disease. In contrast, the medical services available through pediatric departments are generally much better organized. As a result, patients frequently continue in pediatric clinics far into adulthood. Often, adults experience problems, such as hypertension or pregnancy, that are better managed by internists who encounter them regularly. Without an infrastructure to handle their sickle cell disease, patients are naturally reluctant to transfer their care to internists.
Even when an infrastructure exists, in general no orderly procedure exists to transfer care of these patients between comprehensive pediatric programs and their counterparts on the adult services. The consequent disruption in continuity of care often produces problems that could have been prevented. For instance, young adults with sickle cell disease sometimes present with overwhelming pneumococcal sepsis because they had their last immunization by their pediatrician, but failed to connect with an adult provider.
Sickle cell disease is a chronic, and often debilitating disorder. The physical and psychological consequences of chronic illness that begins in childhood often interfere with normal adult functioning. This issue is faced by patients with other chronic illnesses of childhood that extend into the adult years, such as congenital heart disease. A smooth transition process requires a close interface between pediatric and adult providers. Patient trust in adult providers to a large degree depends on a vote of confidence in those physicians by the pediatricians. A good working relationship is the best way to create such confidence. Further, the issue of adult care must be developed slowly for both patient and family. Abrupt transfers are likely to work poorly. The seeds of the concept that the patient will become an adult and will need new providers should be laid early, beginning even as early as 12 years of age.
Our foremost goal as health care providers must be to keep patients in the medical care system. Only then can we execute our second goal, the delivery of true preventative care to patients with sickle cell disease. In this process we must develop programs to assess the psychosocial needs of these young people. Using this information, we can develop specific individual and programmatic interventions. Our key challenge is to avoid having patients "fall through the cracks" as they move between pediatric and adult care. Organized transition programs can facilitate this process
Intermittent episodes of pain are the most consistent manifestation of sickle cell disease. Pain management involves care of both acute and chronic pain. One of the important interventions that has improved the care of patients with sickle cell disease is the institution of a day hospital where acute episodes of pain can be managed without resorting to emergency room care. Many, if not most, episodes of acute vaso-occlusive crisis pain can be controlled such that patients can return home if immediate and aggressive intervention with intravenous analgesics and fluids is undertaken. The day hospital offers at least two advantages over the emergency room. First, treatment can begin quickly, often within minutes of the patient's arrival. The nature of emergency room care means that patients with vaso-occlusive crisis pain may wait for long time periods for evaluation and treatment. Almost as a matter of course, the patient's frustration increases with the rising pain levels during this time. The interaction of an often harried ER physician and a patient with sickle cell disease who has waited for hours to be seen frequently is not congenial.
A second advantage of the day hospital is the staff is familiar with the patients and their analgesic requirements for pain control. This is a key issue in the care of patients with sickle cell disease, some of whom require chronic outpatient therapy with opioids. These patients become tolerized to opioids, and require larger doses of medications than do naive patients. The rotating nature of the staff in most emergency rooms means that patients with sickle cell pain crises often see different providers with each visit. Consequently, patients frequently are undermedicated. An ER physician may (reasonably) be cautious with an unfamiliar patient and begin with 2 mg of intravenous hydromorphone (Dilaudid®), when the patient might require 8 mg every 45 minutes for a total of 5 doses to achieve adequate analgesia. This scenario often evokes a confrontation between patient and staff. The patient demands more medication since the administered amount is inadequate. The staff becomes defensive, and begin to question whether the patient is simply seeking drugs. Hostility develops on both sides. In this context, which is unpleasant for patient and staff, reasonable medical care is not possible.
These factors combine to increase the admission rate to the hospital for patients who are treated for vaso-occlusive pain in the ER versus the day hospital. Dr. Lenette Benjamin presented data from Montefiore Hospital in the Bronx at the 21st Annual Meeting of the Comprehensive Sickle Cell Centers in March, 1999. Over a period of five years, the relative rates of admission for vaso-occlusive pain crises of patients seen in the ER and those seen in the day hospital were 56% and 12% respectively. The lower admission rate from the day hospital saved the hospital about one-half million dollars during this time. For communities with substantial numbers of patients with sickle cell disease, a day hospital treatment facility makes sense both from financial and medical points of view.
- Penicillin prophylaxis
Penicillin prophylaxis in children is probably the most important recent advance in the care of patients with sickle cell disease (1). All patients between the ages of 4 months and 5 years should receive prophylactic penicillin (or erythromycin for children who are allergic to penicillin). A more recent study looking at prophylactic penicillin in older children showed no benefit (2). An extrapolation can be made to adults, who likewise probably do not benefit from prophylactic penicillin.
Patients with sickle cell disease should be immunized with the polyvalent pneumococcal vaccine one every five years . The vaccine does not eliminate overwhelming pneumococcal sepsis, but does reduce the incidence of this deadly complication in children under the age of 2 years (3). The vaccine is recommended in older children and adults, although the evidence for benefit here is less compelling. Immunization against hepatitis B is recommended universally. Patients with sickle cell disease certainly should be included in this recommendation. Children with sickle cell disease may benefit from immunization against Hemophilus influenzae (4). This pathogen is a common in all children but can be deadly in children with sickle cell disease. We do not know whether immunization against Hemophilus influenzae benefits adults.
- Opthalmology Examinations
Proliferative retinopathy is a common and insidious problem for patients with sickle cell disease. Retinopathy correlates with no external manifestations, and particularly does not correlate with vaso-occlusive pain crises. The affected areas of the retina are at the outer margins, far beyond the region visualized with direct opthalmoscopy. For unclear reasons, proliferative retinopathy is more common in people with hemoglobin SC disease than in those with homozygous SS sickle cell disease (5). Patients often have sudden vision loss due to a vitreous hemorrhage as the first manifestation of sickle retinopathy. Some patients with hemoglobin SC disease who have had particularly mild manifestations do not realize that they have a sickle syndrome before sudden vision loss. Laser therapy of proliferative retinopathy can save vision for patients with sickle cell disease. Yearly examinations by an ophthalmologist is true health maintenance.
- Extended Phenotype Blood Matching
Patients with sickle cell disease develop alloantibodies more readily than most people when they are transfused (6). Antibodies can limit the availability of transfusion at times when blood can be life-saving. A significant cause of rapid alloimmunization is that blood donations are made primarily by people of European background. Minor red cell antigens normally present little problem in transfusion and are therefore not looked for with typing and crossmatching. Some of these antigens, such as Kell, Kidd and Duffy, are expressed at different frequencies in people of African ancestry. Some of these problems can be minimized by extended phenotype matching in which the expression of these minor antigens are determined. The closer the antigens of the transfused blood matches that of the recipient, the less likely that problems will occur.
As with any other chronic severe illness, social service support is crucial to the well-being of patients with sickle cell disease. A person who is having trouble finding a place to live, for instance, is unlikely to make many health maintenance visits. The problems faced by people with sickle cell disease include:
- Undereducation. Frequent sickle cell crises often interrupt the education of people with the disorder. The problem is not simply days of school missed. Children with sickle cell disease are often not feeling well even when they are in class. Illness disrupts their concentration and interferes with learning. If children fall behind their peers, educational difficulties mount. The social pressure of being in a class with substantially younger children pushes many youngsters further off the path to education. One approach to the problem of disruptions in schooling has been to have tutors work with children at home and even in the hospital at times. Such an approach requires close cooperation between medical and social service providers. Other innovative strategies are needed to address the crucial issue of education for patients with sickle cell disease.
- Underemployment. People with sickle cell disease are often unemployed or employed at underpaying jobs because of their illness. Undereducation exacerbates the problem. Health providers can help employers develop plans that will allow people with sickle cell disease to work to their fullest potential. Sometimes, this means a flexible schedule that allows for time lost with illness to be made up. Employers should be encouraged to allot adequate time to patients for the health maintenance support they need. Ultimately, this will reduce time lost from the job. "Telecommunting" to jobs is increasingly common in the work place. Home computer links, faxes, and the like allow many people to do the bulk of their work from home. These occupations usually require skills picked up both in the work place and the classroom. Undereducation often makes this type of job inaccessible to people with sickle cell disease. Specialized training can overcome some of these difficulties and allow these patients to fulfill their desire to be productive members of society.
- Medical bureaucracy. The medical bureaucracy grows and becomes more complex daily. People with no serious illness frequently are stymied by the paperwork, restrictions, and regulations that proliferate from both government and private health finance organizations. Patients receive care for crises, but often have difficulty obtaining preventative care, such as ophthalmology examinations. The amount of paperwork can be staggering. Undereducation means that patients often are not equipped to handle these issues. Social support services are crucial to what often is the central part of the lives of people with sickle cell disease. Other areas that impinge on medical care are services such as transportation, which are often called "ancillary". In truth, these services are central to the health care of these patients. Unfortunately, many medical centers and government agencies are cutting the positions of social workers and other people who deal with these issues. Often, these moves are part of cost-cutting efforts. In reality, these maneuvers cost more, due to the consequent reduction in health maintenance and preventative care.
- Basics of Living. Anyone with a chronic illness faces hurtles in life in addition to those in health. The problems of undereducation and underemployment pass through the fulcrum of medial exigency to disrupt much of life's basic fabric. Depression sometimes is the manifestation of these difficulties (7). At other times it is antisocial or self-destructive behavior. A concerted effort by health care and social service providers must include the patient's family and other people important in their social environment.
Depression is often not appreciated in people with sickle cell disease. The condition occurs in children as well as adults (8). Low self-esteem commonly accompanies and exacerbates depression. In this setting, patients often withdraw from family and loved ones, in addition to health care providers (9). The isolation can create a self-perpetuating scenario of low achievement and low expectations. Parenteral frustration is common, most often with adolescents and young adults. Adolescence is a difficult time for many young people. The stress of a chronic illness can produce conflicting tendencies. On one hand, the young person feels a need to assume control of his or her life. On the other, the prospect of facing the barriers created by sickle cell disease is daunting.
Antisocial or self-destructive behavior can take a variety of forms. Missing clinic appointments often reflects an underlying ennui and sense of helplessness. Some patients have the impression that they are unlikely to reach adulthood, much less middle or older age. Whether this results from overt statements by providers during childhood or more subtle cues and signs is unclear. The effect, however, can be striking. Some patients feel that education is a waste of time if they will not get beyond their teenage years anyway. Certainly, preparation for a career would be illogical. A few patients try to use their prescription analgesics for recreational purposes. Fortunately, the need to control pain with these medications makes this behavior less common than is thought by the general medical community. Finally some patients are lured by illicit drugs, such as cocaine. Only a determined effort by all parties concerned with the patient's welfare can turn around the lives of young people who have fallen prey to these traps.
Everyone should make informed decisions about reproduction. As with other people with genetic disorders, patients with sickle cell disease have a number of issues that are specific to their condition. People who are considering children should know about the probabilities of significant genetic disorders in those children. This information requires knowledge about the genotype of both patient and partner. Counseling should be done by trained professionals, and should be non-directive. Our job as health providers is to provide the information relevant to the decision. The patient and partner should then be free to choose the path most comfortable to them.
- Gaston MH, Verter JI, Woods G, et al. 1986. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med 314: 1593-1599.
- Falletta JM, Woods GM, Verter JI, et al. 1995. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. J Pediatr 127:685-690.
- Wong WY, Powars DR, Chan L, et al. 1992. Am J Hematol 39:176-82.
- Ambrosino DM, Landesman SH, Gorham, CC, Siber GR. 1986. Passive immunization against disease due to Haemophilus influenzae type b: concentrations of antibody to capsular polysaccharide in high-risk children. J Infect Dis 153: 1-7.
- Raichand M, Goldberg MF, Nagpal KC, Goldbaum, MH, Asdourian GK. 1977. Evolution of neovascularization in sickle cell retinopathy. A prospective fluorescein angiographic study. Arch Opthalmol 95:1543-1552.
- Rosse WF, Gallagher D, Kinney TR, et al. 1990. Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. Blood 76:1431-1437.
- Ohaeri JU, Shokunbi WA, Akinlade KS, Dare, LO. 1995. The psychosocial problems of sickle cell disease sufferers and their methods of coping. Soc Sci Med 40: 955-960.
- Barbarin OA, Whitten CF, Bonds SM. 1994. Estimating rates of psychosocial problems in urban and poor children with sickle cell anemia. Health Soc Work 19:112-119.
- McCrae JD, Lumley MA. 1998. Health status in sickle cell disease: examining the roles of pain coping strategies, somatic awareness, and negative affectivity. J Behav Med 21:35-55