Tài liệu THE MANAGEMENT OF SICKLE CELL DISEASE ppt

Division of Blood Diseases and Resources THE MANAGEMENT OF SICKLE CELL DISEASE N A T I O N A L N A T I O N A L I N S T I T U T E S H E A R T, L U N G , A N D O F B L O O D H E A L T H I N S T I T U T E THE MANAGEMENT OF SICKLE CELL DISEASE N ATIONAL I NSTITUTES OF H EALTH National Heart, Lung, and Blood Institute Division of Blood Diseases and Resources NIH P UBLICATION N O 02-2117 O RIGINALLY P RINTED 1984 P REVIOUSLY R EVISED 1989, 1995 R EPRINTED J UNE 1999 R EVISED J UNE 2002 (F OURTH E DITION ) II C ONTENTS Preface V Contributors VII Introduction DIAGNOSIS AND COUNSELING World Wide Web Resources Neonatal Screening Sickle Cell Trait 15 Genetic Counseling 19 HEALTH MAINTENANCE Child Health Care Maintenance Adolescent Health Care and Transitions Adult Health Care Maintenance Coordination of Care: Role of Mid-Level Practitioners Psychosocial Management 25 35 41 47 53 TREATMENT OF ACUTE AND CHRONIC COMPLICATIONS 10 11 12 13 14 15 16 17 Pain 59 Infection 75 Transient Red Cell Aplasia 81 Stroke and Central Nervous System Disease 83 Sickle Cell Eye Disease 95 Cardiovascular Manifestations 99 Acute Chest Syndrome and Other Pulmonary Complications 103 Gall Bladder and Liver 111 III 18 19 20 21 22 Splenic Sequestration Renal Abnormalities in Sickle Cell Priapism Bones and Joints Leg Ulcers Disease 119 123 129 133 139 SPECIAL TOPICS 23 24 25 26 27 28 29 IV Contraception and Pregnancy 145 Anesthesia and Surgery 149 Transfusion, Iron Overload, and Chelation 153 Fetal Hemoglobin Induction 161 Hematopoietic Cell Transplantation 167 Genetic Modulation of Phenotype by Epistatic Genes 173 Highlights from Federally Funded Studies 181 P REFACE Enclosed is the fourth edition of a book that is dedicated to the medical and social issues of individuals with sickle cell disease This publication, which was developed by physicians, nurses, psychologists, and social workers who specialize in the care of children and adults with sickle cell disease, describes the current approach to counseling and also to management of many of the medical complications of sickle cell disease Each chapter was prepared by one or more experts and then reviewed by several others in the field Additional experts reviewed the entire volume This book is not the result of a formalized consensus process but rather represents the efforts of those who have dedicated their professional careers to the care of individuals with sickle cell disease The names of the authors, their affiliations, and their e-mail addresses are listed in the front of the book Multiple new therapies are now available for children and adults with sickle cell disease, and often the options to be chosen present a dilemma for both patients and physicians This book does not provide answers to many of these newer questions but rather explains the choices available The book, which focuses primarily on the basic management of indiv- iduals with sickle cell disease and provides relevant online resources at the end of the chapters, is to serve as an adjunct to recent textbooks that delve more deeply into all aspects of the disorder The authors hope that this book will be used by medical students, house staff, general practitioners, specialists, nurses, social workers, psychologists, and other professionals as well as the families and patients who are coping with the complexities of sickle cell disease on a daily basis The book, any part of which can be copied freely, will be placed on the National Heart, Lung, and Blood Institute (NHLBI) Web site and will be updated as needed Research is essential to provide the knowledge required to improve the care of individuals with sickle cell disease, but it is the physicians and other health care personnel who must ensure that the very best care is actually delivered to each child and adult who has this disorder We hope that this book will help to achieve this goal Claude Lenfant, M.D Director, NHLBI V VI C ONTRIBUTORS Robert Adams, M.D Associate Professor, Department of Neurology Room HB-2060 Medical College of Georgia Augusta, GA 30912 Tel: (706) 721-4670 Fax: (706) 721-6757 E-mail: rjadams@neuro.mcg.edu Kenneth I Ataga, M.D Division of Hematology/Oncology CB# 7305, 3009 Old Clinic Building University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7305 Tel: (919) 843-7708 E-mail: kataga@med.unc.edu Harold Ballard, M.D Assistant Chief, Hematology Division New York Veterans Administration Medical Services, 12th Floor New York, NY 10010 Tel: (212) 951-3484 Fax: (212) 951-5981 Lennette Benjamin, M.D Associate Professor of Medicine Montefiore Hospital Medical Center Comprehensive Sickle Cell Center 111 East 210th Street Bronx, NY 10467-2490 Tel: (718) 920-7375 Fax: (718) 798-5095 E-mail: lbenja2725@aol.com Henny Billett, M.D Director, Clinical Hematology Albert Einstein College of Medicine Comprehensive Sickle Cell Center Montefiore Hospital Medical Center 111 East 210th Street Bronx, NY 10467 Tel: (718) 920-7373 Fax: (718) 920-5095 E-mail: billett@aecom.yu.edu E-mail: hbillett@montefiore.org Carine Boehme, M.S Associate Professor The Johns Hopkins University School of Medicine CMSC Room 1004 600 North Wolfe Street Baltimore, MD 21287-9278 Tel: (410) 955-0483 Fax: (410) 955-0484 E-mail: CBOEHM@jhmi.edu Kenneth Bridges, M.D Associate Professor of Medicine Director, Joint Center for Sickle Cell and Thrombosis and Hemostasis Disorders Brigham and Women’s Hospital Harvard Medical School 75 Francis Street Boston, MA 02115 Tel: (617) 732-5842 Fax: (617) 975-0876 E-mail: kbridges@rics.bwh.harvard.edu VII Oswaldo Castro, M.D Professor of Medicine/Pediatrics Howard University School of Medicine Comprehensive Sickle Cell Center 2121 Georgia Avenue, NW Washington DC 20059 Tel: (202) 806-7930 Fax: (202) 806-4517 E-mail: olcastro@aol.com Joseph DeSimone, Ph.D Geneticist VA West Side Medical Center Hematology Research (151C) 820 South Damen Avenue Chicago, IL 60612 Tel: (312) 666-6500 x2683 Fax: (312) 455-5877 E-mail: Jdesimon@UIC.edu Samuel Charache, M.D 2006 South Road Baltimore, MD 21209-4510 Tel: (410) 466-6405 Fax: (410) 466-4330 E-mail: scharach@erols.com Ann Earles, R.N., P.N.P Research Nurse Children’s Hospital of Oakland 747 52nd Street Oakland, CA 94609-1809 Tel: (510) 428-3453 Fax: (510) 450-5635 E-mail: aearles@mail.cho.org Wesley Covitz, M.D Professor of Pediatrics Wake Forest School of Medicine Medical Center Boulevard Winston-Salem, NC 27157-1081 Tel: (336) 716-4267 Fax: (336) 716-0533 E-mail: wcovitz@wfubmc.edu Gary R Cutter, Ph.D Professor of Medicine Director, Center for Research Design and Statistical Methods UNR School of Medicine, Mail Stop 199 Reno, Nevada 89557 Tel: (775) 784-1565 Fax: (775) 784-1142 E-mail: cutterg@prodigy.net Carlton Dampier, M.D Director, Marian Anderson SCC Hematology/Oncology St Christopher’s Hospital for Children Erie Avenue at Front Street Philadelphia, PA 19134 Tel: (215) 427-5096 Fax: (215) 427-6684 E-mail: carlton.dampier@tenethealthcare.com VIII James Eckman, M.D Professor of Medicine Emory University School of Medicine 69 Butler Street Atlanta, GA 30303 Tel: (404) 616-5982 Fax: (404) 577-9107 E-mail: jeckman@emory.edu Morton Goldberg, M.D Director, Department of Ophthalmology The Johns Hopkins Hospital The Wilmer Ophthamological Institute Maumanee Building, Room 729 600 North Wolfe Street Baltimore, MD 21287-9278 Tel: (410) 955-6846 Fax: (410) 955-0675 E-mail: mgoldbrg@jhmi.edu Harry E Jergesen, M.D Department of Orthopaedic Surgery University of California, San Francisco 500 Parnassus Avenue, MU-320W San Francisco, CA 94143 Tel: (415) 476-8938 Fax: (415) 476-1301 E-mail: jergesen@orthosurg.ucsf.edu Chapter 28: Genetic Modulation of Phenotype by Epistatic Genes of sickle hemoglobin in sickle cell anemia When these conditions coexist, there is less hemolysis, and anemia is less severe Clinically, the copresence of α-thalassemia and sickle cell anemia is a paradoxical outcome Vaso-occlusive events appear undiminished in SCD with α-thalassemia, and in some studies, even appeared to be increased Fewer dense and poorly deformable cells as a result of α-thalassemia raise the packed cell volume (PCV), and because the cells contain Hb S, blood viscosity is increased Raising the number of sickle cells, as occurs with α-thalassemia, might promote vaso-occlusion since younger sickle cells are more adherent (a critical phenomenon in painful episodes) (23) On the other hand, a higher PCV may have beneficial effects in some organs, so that skin ulcers of the leg, childhood stroke, and retinal vascular disease may be less common in carriers of α-thalassemia and sickle cell anemia The effect of α-thalassemia on cellular, hematological, and clinical aspects of sickle cell anemia have been reviewed recently (22) Some but not all studies suggest that the combination of α-thalassemia and sickle cell anemia may increase survival (24) A recent followup study of the age-dependency of α-globin gene frequency is compatible with the following interpretation: as medical care improves, the advantage of α-thalassemia on survival disappears, a phenomenon that could explain the contradiction in the available data INTERACTIONS OF β-GLOBIN GENE HAPLOTYPE AND α-THALASSEMIA Some studies have examined how α-thalassemia interacts with different β-globin gene haplotypes to modify the hematological and clinical 176 picture of sickle cell anemia (12,25,26) Most often there is little interaction besides minor reductions in MCV and reticulocyte count and increases in PCV One exception was a study of two western Indian populations with high Hb F levels in which the coexistence of α-thalassemia was associated with milder disease (16) H EMOGLOBIN A Hb A2, the tetramer of α- and δ-globin chains, impairs the polymerization of Hb S to the same extent as the γ-globin chain of Hb F When Hb A2 and Hb F levels are high, the combination of these two hemoglobins may potentially modulate SCD and cause a mild phenotype E RYTHROCYTE G-6-PD D EFICIENCY Glucose-6-phosphate dehydrogenase (G-6PD) deficiency is common in sickle cell anemia In a study of 800 males over age with SCD, G-6-PD deficiency was not associated with differential survival, reduced hemoglobin levels, increased hemolysis, more pain episodes, septic episodes, or a higher incidence of acute anemia episodes (27,28) It now seems clear that there is little, if any, modulation of the phenotype of sickle cell anemia by coincident G-6-PD deficiency, particularly in males where the expression of this X-linked trait is most apparent INHERITED DISORDERS OF THROMBOSIS Some have postulated that thrombosis and hemostasis could play roles in the pathophysiology of SCD Coincidental mutations that favor blood coagulation or thrombosis could influence disease phenotype (29), particularly the occurance of SCD-related stroke Recent studies attempting to relate the presence of mutations in genes for factor V, platelet glycoprotein IIIa, and 5,10 methylenetetrahydrofolate reductase (MTHFR) to the pathogenesis of specific complications of SCD have had disparate results In one report, a C→T mutation at position 677 of the MTHFR gene that is associated with enzyme thermolability and a putative hypercoagulabile state due to hyperhomocystenemia was found in 36 percent of 45 adults with SCD and osteonecrosis but in only 13 percent of 62 SCD patients without osteonecrosis—a significant difference (30) However, smaller studies reported that the same mutation was not associated with vascular complications of SCD, including osteonecrosis and stroke (31-33) Studies of the platelet glycoprotein IIIa gene have not found a link between a C→T mutation at position 1565 (which is associated with premature coronary artery disease) and osteonecrosis Factor V Leiden, a common cause of thrombosis in Caucasians, is rare in African Americans; limited studies have not linked this mutation to stroke in SCD High levels of antiphospholipid antibodies were found in patients with SCD and individuals with sickle cell trait (33), but no relationship to disease complications was noted Clearly, further work is needed to resolve the role of genetic risk factors for thrombosis, many of which have been examined only in pilot studies or reported in abstract The potential genetic contribution to stroke risk in SCD can be estimated from clinical stroke risk observed in sibling pairs with SCD In 210 pairs among 2,353 patients with SCD, 167 pairs had no history of stroke, 33 pairs had a stroke in one sib, and 10 pairs had history of stroke in both sibs (34) A case-control candidate gene association study involving patients with SCD and ischemic stroke suggested an association with ischemic stroke and angiotensinogen repeat alleles and (p