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Sickle Cell Anemia Treatment INFECTION Serious bacterial infections are a major cause of morbidity and mortality in patients with sickle cell disease. Severe, overwhelming septicemia/meningitis due to S. pneumoniae is the most common cause of death during early childhood, but enteric organisms emerge as important pathogens in older patients. Because of the patient’s asplenic condition, and because of disordered humoral immunity, infections in patients with SS disease are more likely to cause morbidity, disseminate, and resist eradication than in individuals unaffected by the disease. Infections also may enhance susceptibility toward vasoocclusive complications. Prevention and early, aggressive treatment of infection are critical in the management of patients with sickle cell disease.PREVENTION Immunization Children with SS disease have a normal antibody response to vaccines and should receive all immunizations recommended by the American Academy of Pediatrics (these change periodically, and the most current recommendations should be followed (see Table 2)). In addition, children should receive pneumococcal vaccine. Some clinicians recommend that the influenza vaccine be administered according to epidemiologic considerations.Antibiotic Prophylaxis Prophylactic penicillin is so effective in reducing the number of lifethreatening episodes of pneumococcal sepsis in children with SS disease under age 5 years that most States screen newborns for the disease so they can be placed on the drug by 2 to 3 months of age. Oral penicillin VK (125 mg given twice a day up to age 3 years, then 250 mg given twice a day) is the preferred form of treatment.Prophylaxis should be given to children with SS disease and Sb o thal starting at 2 to 3 months of age and continuing until at least age 5 years. Prophylaxis in older children has not been shown to be beneficial and may be unnecessary after pneumococcal immunizations are complete and antibody titers are protective. Some clinicians give prophylaxis to children with SC disease or Sb + thal: there is an increased risk of severe infection in such patients, although it is less than in SS disease or Sb o thal. Compliance with penicillin prophylaxis can be achieved, provided that a dedicated team of physicians, nurses, and health care educators engage families in intensive educational programs.
Neither the pneumococcal vaccine nor available antibiotics has been shown to eliminate nasopharyngeal colonization with S. pneumoniae, Neisseria meningitis, and H. influenzae in normal young children or those with sickle cell disease. Prophylactic antibiotics prevent bacteremia and tissue invasion, despite continued nasopharyngeal carriage or reexposure. When failure occurs, it may be due to a variety of microbiologic causes as well as a lack of patient compliance. As discussed below, the emergence of penicillin and cephalosporinresistant S. pneumoniae is a serious evolving problem in many communities and may ultimately undermine the effectiveness of the established prophylactic regimen. Clinicians should be aware that recommendations concerning the use of prophylactic penicillin and the choice of empiric antibiotics in patients with sickle cell disease may well undergo tremendous change during the next few years. At present, the most effective approach is a combination of traditional pneumococcal vaccination and regular penicillin prophylaxis; it is hoped that newer conjugated pneumococcal vaccines will prove protective in infancy. MANAGEMENT Pediatric Infection Fever in a child younger than age 5 years with SS disease often indicates lifethreatening bacterial infection. It is estimated that there is a 400fold increased risk of pneumococcal septicemia/meningitis in this population. Fortunately, H. influenzae infections have become exceedingly rare with the advent of the H. influenzae vaccine.Children with sickle cell disease and septicemia generally have fever greater than 102 o F (38.9 o C), but temperatures below 102 o F may also be seen, especially early in the clinical course. In febrile children with sickle cell disease, administration of antibiotics should occur promptly, even for minimal clinical indications such as significant fever, chills, etc. The patient should be evaluated for causes of fever such as otitis media, pneumonia, or urinary tract infection. Chest xray, blood, urine, and throat cultures should be obtained without waiting for test results. Lumbar puncture should be performed even if there are only minimal indications of meningitis. An antibiotic effective against S. pneumoniae and H. influenzae should be promptly administered, preferably intravenously. Because penicillin and cephalosporinresistant S. pneumoniae are now identified in many regions of the country, antibiotics such as vancomycin have been added to the typical empiric therapy regimen in those areas. It is critical to be aware of the susceptibility patterns of the local flora when selecting empiric therapy. The choice of subsequent antibiotics can be guided by results of cultures and clinical course. Practice varies widely on indications for admitting febrile SS children to the hospital. There is, however, consensus that all SS children with any of the following be admitted for inpatient treatment:
Infections in Older Children and Adults Because pneumococcal infections become less frequent after the first decade of life and infections due to other pathogens found in the general population become more common, a systematic bacteriologic evaluation should be used before administering antibiotics. A persistent fever higher than 101 o F should not be assumed to be due to vasoocclusive crisis. Infections tend to occur in already damaged areas such as lungs, kidneys, and bones.Urinary Tract Infections Pyelonephritis in patients with SS disease is difficult to treat, recurs regularly, and is often associated with septicemia. This is particularly serious during pregnancy. Urine cultures are essential before therapy and should be repeated 1 to 2 weeks after cessation of therapy. Treatment consists of antibiotics and hydration. Urologic evaluation and chronic suppressive antibiotic therapy may be appropriate for patients with repetitive infection.Osteomyelitis Osteomyelitis must be differentiated from the more common (~50:1) diaphyseal bone infarction because the two conditions present with similar clinical and imaging findings but are treated differently. Similarly, septic arthritis must be distinguished from the more common joint effusion associated with acute painful episodes. It is essential to establish a bacterial diagnosis (from blood or aspirated joint or subperiosteal fluid) before longterm antibiotics are started to treat osteomyelitis or septic arthritis. Blood cultures may be particularly helpful in the setting where infarcted bone is seeded during an episode of bacteremia.Increasing antibiotic resistance among Salmonella isolates is a major problem. Even if in vitro susceptibility tests suggest efficacy for tetracyclines, cephalosporins, and aminoglycosides, these antibiotics often fail. Ampicillin, quinolines, and trimethoprimsulfamethoxazole have been demonstrated to be effective (when indicated by in vitro sensitivity tests). Chloramphenicol can also be effective, but its potential for bone marrow suppression requires frequent monitoring of the reticulocyte count. The tendency of Salmonella to establish chronic, intracellular infection requires prolonged treatment—typically 1 month of intravenous antibiotic therapy, followed by months of oral treatment. Public health procedures should be implemented to prevent spread of infection to family members. Bacteriologically proven staphylococcal osteomyelitis requires highdose penicillinase resistant penicillin (e.g., nafcillin) for several weeks. If adequate blood levels of the antibiotic can be achieved, a regimen such as 2 weeks of intravenous therapy followed by 4 to 6 weeks of oral therapy can be given. The necessity for surgical incision and drainage or débridement in osteomyelitis of any cause should be based on clinical judgment. BIBLIOGRAPHY Breiman RF, Butler JC, Tenover FC, Elliott JA, Facklam RR. Emergence of drugresistant pneumococcal infection in the United States. JAMA 1994;271:18315.Gaston MH, Verter JI, Woods G, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. N Engl J Med 1986;314:1593. Leggiadro RJ. Penicillin and cephalosporinresistant Streptococcus pneumoniae and emerging microbial threat. Pediatrics 1994;93:5003. Overturf GD, Powars D, Baraff LJ. Bacterial meningitis and septicemia in sickle cell disease. Am J Dis Child 1977;131:7847. Pearson HA, Gallagher D, Chilcote R, et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 1985;76:3927. Sarnaik S, Kaplan J, Schiffman G, et al. Studies on pneumococcal vaccine alone or mixed with DTP and on pneumococcus type 6B and Haemophilus influenzae type b capsular polysaccharidetetanus toxoid conjugates in two to fiveyearold children with sickle cell anemia. Pediatr Infect Dis 1990;9:1816 (erratum, Pediatr Infect Dis 1990;9:308). Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991;325:145360. Wilimas JA, Flynn PM, Harris S, et al. A randomized study of outpatient treatment with ceftriaxone for selected febrile children with sickle cell disease. N Engl J Med 1993;329:4726. Zarkowsky HS, Gallagher D, Gill FM, et al. Bacteremia in sickle hemoglobinopathies. J Pediatr 1986;109:57985.
TRANSFUSIONS Transfusion should be used for specific indications in the treatment of patients with sickle cell disease and should be used as sparingly as possible. Transfusion is indicated for certain acute problems (not including acute painful episodes) or for the treatment or prevention of chronic complications and other healthrelated events. Several methods of transfusion are available (simple transfusion, partial exchange, and chronic exchange); the method used depends on the indication for the transfusion. The recommendations in this discussion are for patients with homozygous SS disease and Sb o thal. The role of transfusion in the care of patients with Hb SC disease and Hb Sb + thalassemia is controversial.An important principle in the transfusion of sickle cell patients is the avoidance of excessive blood viscosity. Blood viscosity is a function of the intrinsic viscosity of the red blood cells and of the hematocrit. Because sickle cells are intrinsically less deformable than normal cells, raising the hematocrit without substantially reducing the proportion of sickle cells may raise the blood viscosity to dangerous levels. Therefore, simple transfusions should be used with caution in patients with high hematocrits, and the final posttransfusion hematocrit should be 36 percent or less. Patients with high baseline hemoglobin may be more safely transfused using an exchange technique. INDICATIONS FOR TRANSFUSIONS The following are generally considered to be indications for red blood cell transfusions in sickle cell disease:
EQUIVOCAL INDICATIONS Transfusion is sometimes suggested for a number of conditions in which its efficacy is unproved. If transfusion is done in these conditions, it should be an exchange transfusion. These conditions include the following:
NONINDICATIONS AND CONTRAINDICATIONS The following are not considered appropriate indications for transfusion, and transfusion is not recommended in these clinical settings:
TYPES OF BLOOD PRODUCTS TO BE USED Standard bank blood is appropriate for the patient with sickle cell disease. The “age” of the blood (time since collection) is usually not important as long as it is within limits set by the transfusion service. Exchange transfusion with blood less than 5 days old (less than 3 days old in the small infant) helps in acute situations requiring immediate correction of the oxygen carrying capacity. All blood should be screened for the presence of sickle hemoglobin and confirmed to be negative. A solubility test is adequate for screening in this situation. This procedure eliminates blood with sickle cell trait, which will confuse later measurements of the proportion of sickle cells or Hb S. The antigenic phenotype of the red cells (at least ABO, Rh, Kell, Duffy, Kidd, Lewis, Lutheran, P, and MNS groups) should be determined in all patients older than 6 months of age. A permanent record of this should be maintained in the Blood Bank, and a copy of the record should be given to the patient or family.All patients with a history of prior transfusion should be screened for the presence of alloantibodies. The efficacy of a chronic transfusion program should be assessed periodically by determining the proportion of Hb S by quantitative hemoglobin electrophoresis as well as the hemoglobin concentration or hematocrit. Red blood cell preparations depleted of leukocytes by filtration are recommended because of the reduction in febrile reactions and decreased alloimmunization to leukocyte antigens. Washed red blood cells should be used in patients who have a history of severe allergic reactions (bronchospasm) following prior transfusions. The use of autologous blood transfusions in sickle cell disease should be avoided. Blood relatives should not be used as blood donors for children who may be candidates for bone marrow transplantation. TRANSFUSION METHODS Simple Transfusion Simple transfusions can be used for acute anemia or hypovolemia or in a chronic transfusion program. Packed red blood cells should not be used when only volume expansion is needed.Exchange Transfusion Exchange transfusion is used to alter the hemoglobin level rapidly and to replace sickle cells with normal erythrocytes. This type of transfusion reduces the concentration of sickle cells without substantially increasing the hematocrit or whole blood viscosity. Several methods are available that achieve this purpose.Rapid Partial Exchange In some patients, whole blood can be removed from one arm at the same time that donor cells are transfused into the other arm. In adults, this procedure can be performed in 500 mL units. In children, the individual exchange aliquots are adjusted to a safe and practical level.The total volume of blood to be used is proportional to the patient’s body weight and hematocrit; thus, different formulas are needed for different initial hematocrit ranges. Exchange transfusions performed with whole blood (or, more commonly, packed cells reconstituted to the volume and hematocrit of whole blood using saline or other diluents) are more efficient than those using packed cells. They may reduce the number of units needed but take slightly more time. In children, a practical estimate of the volume required for exchange (whole blood or packed cells reconstituted to a hematocrit of 30 to 40 percent) is 50 60 mL/kg. In adults, blood can be removed from the patient in 500 mL aliquots, followed by infusion of 500 mL of reconstituted blood; this may be repeated for six to eight units of transfusion. Alternatively, the following technique can be used: Step 1. Bleed one unit (500 mL) of blood from the patient, infuse 500 mL of saline.Step 2. Bleed a second unit from the patient, infuse two units of blood.Step 3. Repeat steps 1 and 2; if the patient has a large red blood cell mass, repeat once more. The devices used in plasmapheresis can be used to exchange transfuse patients efficiently; red blood cells are removed at the egress and normal blood is infused at the ingress. Usually six to eight units of blood are needed to exchange an adult; formulae are available to calculate the exact amount needed depending on body size, hematocrit, desired hematocrit, and desired percentage of Hb A. Such devices can be used for pediatric patients if the size of the receptacle is sufficiently small so as not to remove too much blood at one time.Care must be taken in all cases where exchange transfusion is used to be certain that the final hemoglobin level does not exceed 1012 g/dL to avoid the problems of hyperviscosity. Careful monitoring of the level of hemoglobin and of the percentage of Hb A is necessary to be certain that the goals of the transfusion have been met. Chronic Transfusion Programs Once a sufficient level of transfused normal cells (greater than 50 to 70 percent Hb A) is achieved, it is often useful to maintain this for a period of weeks to years. This proportion of normal cells can be maintained by simple transfusions at intervals of 2 to 4 weeks. The level of Hb A must be monitored by quantitative hemoglobin electrophoresis.TRANSFUSION COMPLICATIONS Transfusion complications for sickle cell patients are the same as those for any patient receiving acute or chronic transfusion.Volume Overload This occurs when too much volume is transfused too quickly. Congestive heart failure and pulmonary edema are most likely to occur in patients who have cardiac dysfunction or minimal cardiac reserve. Administration of intravenous furosemide and partial removal of red cell preservingfluid before transfusion and a slow transfusion rate can help in preventing this serious problem.Iron Overload The serum ferritin levels should be measured periodically. If the level exceeds 2,000 ng/mL (usually after 1 to 3 years of chronic transfusion) and transfusions are still required, patients should be considered for chronic chelation therapy using Desferal. Complications of deferoxamine therapy may include ototoxicity, ophthalmic toxicity, allergic reactions, growth failure, unusual infections (Yersinia, fungi), and pulmonary hypersensitivity. Poor patient compliance, because of repeated subcutaneous infusions of medications, is a significant problem with chronic chelation therapy. Ongoing education and support, often provided by a specially trained nurse, is usually necessary to maintain the patients’ cooperation. A subcutaneous infusion port or a Hickman catheter may be used for parenteral access. Desferal therapy should be discontinued during acute bacterial infections. A new oral iron chelator (L1) is currently being evaluated for safety and efficacy.Alloimmunization and Delayed Hemolytic Transfusion Reactions The incidence of alloimmunization to red blood cell antigens in transfused patients with sickle cell anemia is approximately 20 to 25 percent, which is greater than in the general population. This condition causes difficulty in obtaining compatible blood and results in a high incidence of delayed hemolytic transfusion reactions. The delayed transfusion reaction occurs 5 to 20 days after transfusion and is due to antibodies not detectable at the time of compatibility testing. It has been found that 30 percent or more of the antibodies to red blood cell antigens may disappear with time, although the recipient remains capable of mounting an anamnestic response to further stimulation by transfusion. The delayed hemolytic transfusion reaction that can result may cause severe anemia, onset of painful crisis, or even death.ACUTE HEMOLYTIC TRANSFUSION REACTIONS Acute hemolytic transfusion reactions in sickle cell patients are not different in cause from those in other patients. Major hemolytic reactions occur primarily with major blood group (ABO) mismatches and must be treated aggressively to maintain blood pressure and glomerular filtration; most can be prevented by avoiding clerical and patient or sample identification errors in the crossmatching and transplantation of units from donor site to the patient. Minor hemolytic reactions occur when the amount of antibody in the serum is limiting, and they are characterized by the disappearance of the transfused blood during a period of several days (with a consequent decrease in the hematocrit) and the appearance of hyperbilirubinemia; no further treatment is necessary except monitoring the hematocrit level to ensure that it does not greatly decrease.Any of these reactions, particularly the delayed variety, are able to initiate a painful episode in the patient with sickle cell disease. In all cases, the patient’s blood should be examined very carefully by immunohematologists in the transfusion service to document the antibody or antibodies responsible for the reaction; the patient must be made aware of the complication and be given a card describing the antibodies found. Alloimmunization and hemolytic transfusion reactions resulting from it can be reduced by the following:
Autoimmune Anemia Following Allosensitization In some highly alloimmunized patients, a syndrome of autoimmune hemolytic anemia may follow allosensitization or a hemolytic transfusion reaction. In this case, the patient may become more anemic than before transfusion, and the direct antiglobulin (Coombs’) test remains positive even after the incompatible transfused cells have been destroyed. This syndrome occurs because the body produces antibodies against selfantigens, and it may persist from several weeks to 2 to 3 months before disappearing. Further transfusion is complicated by the autoimmune antibody and requires sophisticated bloodbanking techniques to find the “least incompatible” blood for transfusion.Alloantibodies to White Cells, Platelets, and Serum Proteins Patients who are transfused may become alloimmunized to antigens present on leukocytes and/or platelets but lacking on red blood cells. Such antibodies may cause a febrile reaction that can be prevented through the removal of the leukocytes by filtration or washing. These antibodies as well as those against serum proteins can cause allergic reactions that can be prevented by prophylaxis with an antihistamine (Benadryl ® ), removal of leukocytes or plasma by washing, or use of other measures previously noted.Infection Hepatitis and other transfusiontransmitted viral diseases in blood occur with the same frequency in sickle cell patients as in other patients receiving transfusions. The effects may be more severe in sickle cell patients because of the presence of the disease. Patients receiving multiple transfusions should be serially monitored for hepatitis C and other viral infections; alpha interferon may be useful in the treatment of patients with chronic hepatitis B and C.Posttransfusion human immunodeficiency virus (HIV) infection and AIDS are reported in sickle cell disease, occurring as late as 5 to 8 years after the transfusion with blood not known to be from an infected donor. Thus, patients with sickle cell disease who were transfused before blood products were tested for HIV antibodies (197585) as well as those transfused with today’s “safe” blood should be considered for counseling on testing for HIV infection. TRANSFUSION FOR SURGERY A multiinstitutional study recently prospectively compared perioperative complication rates of sickle cell anemia patients randomized to aggressive transfusion (decrease Hb S below 30 percent) and conservative transfusion (Hb S approximately 60 percent, Hb to 10 g/dL). Serious complications occurred in approximately onethird of both groups. The most common complication was acute chest syndrome, which occurred in 10 percent of patients. There were no significant differences between transfusion regimens and any complication except transfusion complications, which occurred in 14 percent of aggressively transfused patients and 7 percent of conservatively managed patients. In addition, preoperative hospitalization days attributed to transfusion preparation were 4 days in the aggressively transfused patients compared with approximately 2 days in conservatively managed patients. In conclusion, present data suggest that routine hemoglobin SS patients undergoing major elective surgery should be conservatively transfused as part of their routine management. Transfusion with limited phenotypic units would most likely eliminate the alloimmunization observed from E, K, C, and Fya. Definitive data to recommend no preoperative transfusion in sickle cell disease are not available. However, the present standard of practice suggests that no preoperative transfusion is a possible alternative in healthy hemoglobin SC patients and for limited surgery in stable hemoglobin SS patients. At present, patients having tonsillectomies and adenoidectomies should be transfused for surgery.BIBLIOGRAPHY Ambruso DR, Githens JH, Alcorn R, et al. Experience with donors matched for minor blood group antigens in patients with sickle cell anemia who are receiving chronic transfusion therapy. Transfusion 1987;27:94.Bischoff RJ, Williamson A III, Dalali MJ, et al. Assessment of the use of transfusion therapy perioperatively in patients with sickle cell hemoglobinopathies. Ann Surg 1988;207:4348. Brittenham GW, Cohen AR, McLaren CE, et al. Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 1993;42:815. Castro O, FinkeCastro H, Coats D. Improved method for automated red cell exchange in sickle cell disease. J Clin Apheresis 1986;3:939. Cohen A. Treatment of transfusional iron overload. Am J Pediatr Hematol Oncol 1990;12:48. Cohen AR, Martin MB, Silber JH, Kim HC, OheneFrempong K, Schwartz E. A modified transfusion program for prevention of stroke in sickle cell disease. Blood 1992;79:165761. Comer GM, Ozick LA, Sachdev RK, et al. Transfusionrelated chronic liver disease in sickle cell anemia. Am J Gastroenterol 1991;86:12324. Cox JV, Steane E, Cunningham G, Frenkel EP. Risk of alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease. Arch Intern Med 1988;148:24859. Cummins D, Webb G, Shah N, Davies SC. Delayed haemolytic transfusion reactions in patients with sickle cell disease. Postgrad Med J 1991;67:68991. Epps CH Jr, Bryant DD III, Coles MJ, Castro O. Osteomyelitis in patients who have sickle cell disease. Diagnosis and management. J Bone Joint Surg 1991;73:128194. Fullerton MW, Philippart AI, Sarnaik S, Lusher J. Preoperative exchange transfusion in sickle cell anemia. J Ped Surg Greenwalt TJ, Zelenski KR. Transfusion support for haemoglobinopathies. Clin Haematol 1984;13:151. Koshy M, Burd L, Wallace D, Moawad A, Baron J. Prophylactic redcell transfusions in pregnant patients with sickle cell disease. A randomized cooperative study. N Engl J Med 1988;319:144752. Mintz PD, Williams ME. Cerebrovascular accident during a delayed hemolytic transfusion reaction in a patient with sickle cell anemia. Ann Clin Lab Sci 1986;16:214. Orlina AR, Sosler SD, Koshy M. Problems of chronic transfusion in sickle cell disease. J Clin Apheresis 1991;6:23440. Piomelli S. Chronic transfusion in patients with sickle cell disease. Implications and problems. Am J Pediatr Hematol Oncol 1985;7:51. Piomelli S, Seaman C, Ackerman K, Blei F. Planning an exchange transfusion in patients with sickle cell syndromes. Am J Pediatr Hematol Oncol 1990;12:26876. Rackoff WR, OheneFrempong K, Month S, Scott JP, Neahring B, Cohen AR. Neurologic events after partial exchange transfusion for priapism in sickle cell disease. J Pediatr 1992;120:8825. Reisner EG, Kostyu DD, Phillips G, et al. Alloantibody responses in multiply transfused sickle cell patients. Tissue Antigens 1987;30:161. Rosse WF, Gallagher D, Kinney TR, et al. Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. Blood 1990;76:14317. Schmalzer EA, Lee JO, Brown AK, et al. Viscosity of mixtures of sickle and normal red cells at varying hematocrit levels. Implications for transfusion. Transfusion 1987;27:228. Silliman CC, Peterson VM, Mellman DL, Dixon DJ, Hambidge KM, Lane PA. Iron chelation by deferoxamine in sickle cell patients with severe transfusioninduced hemosiderosis: a randomized, doubleblind study of the doseresponse relationship. J Lab Clin Med 1993;122:4854. Sosler SD, Jilly BJ, Saporito C, Koshy M. A simple, practical model for reducing alloimmunization in patients with sickle cell disease. Am J Hematol 1993;43:1036. Talacki CA, Ballas SK. Modified method of exchange transfusion in sickle cell disease. J Clin Apheresis 1990;5:1837. Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med 1990;322:161721. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. N Engl J Med 1995;333(4):20613. Wang WC, Kovnar EH, Tonkin IL, et al. High risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease. J Pediatr 1991;118:37782. Wayne AS, Kevy SV, Nathan DG. Transfusion management of sickle cell disease. Blood 1993;81:110923.
SURGERY AND ANESTHESIA Patients with sickle cell disease who undergo surgery have an increased risk of perioperative complications. Careful preoperative preparation of the patient by a team consisting of a surgeon, hematologist, and anesthesiologist will minimize or eliminate these complications.PREEXISTING HEALTH OF THE PATIENT Patients with organ damage and/or coexistent disease must be identified because they are at increased risk for perioperative complications.In particular, older patients, those with a history of pulmonary or CNS disease, recurrent hospitalizations, and/or those who have been previously heavily transfused are at high risk for perioperative complications, especially acute chest syndrome and vasoocclusive events. A physical examination and chart review should be supplemented by the following tests:
TYPES OF SURGERY Surgical procedures that have an increased probability of ischemia or hypoxia deserve special attention. These include cardiothoracic surgery; techniques associated with hypotension, hypothermia, and hyperventilation; and vascular surgery. Laparascopic surgery appears to lower the postoperative complications of sickle cell disease and should be used in appropriate settings.PREOPERATIVE CARE All patients should be evaluated by the anesthesiologist the day before surgery. Patients requiring general anesthesia should receive maintenance fluids at least 12 hours before surgery, with strict attention paid to urinary output and weight. Preoperative assessment of the patient should include checking for signs of vasoocclusion, fever, infection, and dehydration. The laboratory and physical examination results should be reviewed to identify abnormalities in the heart, liver, kidneys, brain, and lungs.INTRAOPERATIVE MANAGEMENT All patients should be monitored with at least an EKG and have a determination of inspired oxygen concentration by pulse oximetry or blood gas testing. Measurements of electrolyte and urine output and invasive hemodynamic monitors may be required, depending on the patient’s clinical status and the type of surgery. A warm temperature should be maintained in the operating room. General anesthesia should aim for a mild respiratory alkalosis (pH about 7.45) and a normothermic, wellhydrated patient. The patient should receive a minimum of 50 percent oxygen in combination with the anesthetic agent. Blood replacement for significant intraoperative blood loss is recommended. Intraoperative blood salvage techniques (cell savers) are not recommended.Postoperatively, oxygen should be administered until the effects of anesthesia have worn off. Patients who have surgical wounds that interfere with respiration may require an extended use of oxygen. Continued monitoring by oximetry is recommended in the recovery room and/or intensive care unit. Postoperative parenteral hydration should keep the patient at 1 to 1˝ times maintenance. Aggressive respiratory care is necessary in sickle cell disease to minimize pulmonary complications. BIBLIOGRAPHY Bischoff RJ, Williamson A III, Dalali MJ, et al. Assessment of the use of transfusion therapy perioperatively in patients with sickle cell hemoglobinopathies. Ann Surg 1988;207:4348.Burrington JD. Elective and emergency surgery in children with sickle cell disease. Surg Clin North Am 1976;56:5571. Esseltine DW, Baxter M, Bevan JC. Sickle cell states and the anesthesiologist. Can J Anaesth 1988;35:385403. Fullerton MW, Philippart AI, Sarnaik S, Lusher J. Preoperative exchange transfusion in sickle cell anemia. J Ped Surg 1981;16:297300. Gibson J. Anesthesia for sickle cell disease and other hemoglobinopathies. Semin Anesth 1987;6:2735. Homi J. General anesthesia in sickle cell disease. Br Med J 1979;1:15991601. Janik J, Seeler RA. Perioperative management of children with sickle hemoglobinopathy. J Pediatr Surg 1980;15:11720. Koshy M, Weiner SJ, Miller ST, et al. Surgery and anesthesia in sickle cell disease. Blood 1995;86(10). National Institutes of Health. NIH Consensus Development Conference Statement From Perioperative Red Cell Transfusion. Vol. 7, No. 4, June 2729, 1988. Searle JF. Anesthesia in sickle states. Anaesthesia 1973;28:4858. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. N Engl J Med 1995;333(4):20613. Ware R, Filston HC, Schultz WH, Kinney TR. Elective cholecystectomy in children with sickle hemoglobinopathies: successful outcome using preoperative transfusion regimen. Ann Surg 1988;208:1735.
EXPERIMENTAL THERAPY The lifespan of patients with SS disease has increased significantly in the past 30 to 40 years, partly because of improvements in the general health of all citizens and therapeutic approaches. Today, the median survival of Hb SS patients is about 45 years. Further improvements in the quality of life and of the lifespan will come from treatments such as penicillin prophylaxis and others that must be considered experimental at the present time. Faced with severely ill patients who have the most to gain and the least to lose from experimental therapy, health providers and patients must consider the options available. Patients should be involved in a therapeutic trial whenever possible. In all cases, patients must be carefully informed of potential risks and benefits of the proposed therapy. Treatment should be carried out by physicians with experience in sickle cell disease, the use of the therapy involved, and in the conduct of experimental therapeutic trials.HYDROXYUREA Fetal hemoglobin (Hb F) interferes with the polymerization of Hb S in solution and with the sickling of Hb SS red blood cells. Hydroxyurea, a cytotoxic chemotherapeutic agent, was shown to augment Hb F production in SS patients in a preliminary trial, without serious toxicity. To date, no trials have been carried out in patients with SC disease or Sb thal. The mechanism of action is still unclear but probably involves altered proliferation of early red blood cell precursors capable of increased Hb F synthesis. A doubleblind multicenter trial has recently concluded that use of the drug can reduce the frequency of painful episodes by almost 50 percent. With longterm risks poorly understood, the caveats described above should be followed. Other drugs such as erythropoietin and butyrate derivatives may be capable of augmenting Hb F production by other means. Their role in therapy, alone or combined with hydroxyurea, is still unclear.BONE MARROW TRANSPLANTATION Successful bone marrow transplantation can cure sickle cell anemia, and initial reports from Europe suggest that transplantation can be carried out with relatively low morbidity and mortality. Most investigators agree that transplantation should be considered for severely affected children; the dilemma is that severely affected patients are poor risks for an arduous procedure. At present, unrelated donors should not be used, and the availability of compatible sibling donors is limited. A national collaborative study of transplantation in pediatric patients in the United States, with strictly defined criteria for eligibility, is currently under way; preliminary results are somewhat encouraging. Umbilical cord blood may prove to be an important resource for stem cell transplantation in sickle cell disease.It is hoped that such studies will permit a definition of risk factors and improved eligibility criteria for bone marrow transplantation in Hb SS patients just as risk factors and eligibility criteria for bone marrow transplantation have been defined for patients with thalassemia major. Costbenefit analyses, in terms of health and wellbeing of patients and financial outlays for individual patients and for society as a whole, also will emerge from this ongoing research. PROPHYLACTIC TRANSFUSION TO PREVENT STROKE Transcranial Doppler studies can demonstrate arterial narrowing in SS patients who subsequently have strokes. A randomized trial is currently under way to determine whether chronic transfusion therapy can prevent first strokes in children with abnormal Doppler studies.GENETIC ENGINEERING Once fanciful, gene therapy now seems a very possible future development. Basic laboratory studies are under way, but it appears unlikely that application to patients will be possible for a number of years.IMPORTANCE OF ONGOING CLINICAL RESEARCH The foregoing reaffirm that our current therapy provides patients with sickle cell disease some solace but not enough to prevent an uncertain future. Most of our patients and their families know the current therapeutic limitations; however, knowledge that new treatments are under active investigation may make that burden somewhat lighter and provide them with reason to hope.BIBLIOGRAPHY Adams RJ, McKie V, Nichols FT, et al. The use of transcranial ultrasonography to predict stroke in sickle cell disease. N Engl J Med 1992;326:60510.Castro O, Brambilla DJ, Thorington B, et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood 1994;84:6439. Charache S, Terrin ML, Moore RD, et al. Effects of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 1995;332:131720. Johnson FL, Mentzer WC, Kalinyak KA, et al. Bone marrow transplantation for sickle cell disease: the United States experience. Am J Pediatr Hematol Oncol 1994;16:226. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994;330:163944. Platt OS, Thorington BD, Brambilla DJ, et al. Pain in sickle cell disease: rates and risk factors. N Engl J Med 1991;325:116. Vermylen C, Cornu G. Bone marrow transplantation for sickle cell disease: the European experience. Am J Pediatr Hematol Oncol 1994;16:1821. Vichinsky EP, Lubin BH. A cautionary note regarding hydroxyurea in sickle cell disease. Blood 1994;83:11248. Walters MC, Bernaudin F, Johnson FL, et al. Neurologic complications following allogeneic bone marrow transplantation for sickle cell anemia. Blood 1993;82(suppl 1):417a. |
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