Chapter 099. Disorders of Hemoglobin (Part 14)

Deferasirox is a promising oral iron-chelating agent. Single daily doses of 20 or 30 mg deferasirox produced reductions in liver iron concentration comparable to desferoxamine in chronically transfused adult and pediatric patients. Deferasirox produces some elevations in liver enzymes and slight but persistent increases in serum creatinine, without apparent clinical consequence. Other toxicities are similar to those of desferoxamine. Its toxicity profile is acceptable, although long-term effects are still being evaluated.Bone Marrow Transplantation, Gene Therapy, and Manipulation of HbFBone marrow transplantation provides stem cells able to express normal hemoglobin; it has been used in a large number of patients...
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Chapter 099. Disorders of Hemoglobin (Part 14) Chapter 099. Disorders of Hemoglobin (Part 14) Deferasirox is a promising oral iron-chelating agent. Single daily doses of20 or 30 mg deferasirox produced reductions in liver iron concentrationcomparable to desferoxamine in chronically transfused adult and pediatricpatients. Deferasirox produces some elevations in liver enzymes and slight butpersistent increases in serum creatinine, without apparent clinical consequence.Other toxicities are similar to those of desferoxamine. Its toxicity profile isacceptable, although long-term effects are still being evaluated. Bone Marrow Transplantation, Gene Therapy, and Manipulation ofHbF Bone marrow transplantation provides stem cells able to express normalhemoglobin; it has been used in a large number of patients with β-thalassemia anda smaller number of patients with sickle cell anemia. Early in the course ofdisease, before end-organ damage occurs, transplantation is curative in 80–90% ofpatients. In highly experienced centers, the treatment-related mortality is Aplastic and Hypoplastic Crisis in Patients with Hemoglobinopathies Patients with hemolytic anemias sometimes exhibit an alarming decline inhematocrit during and immediately after acute illnesses. Bone marrow suppressionoccurs in almost everyone during acute inflammatory illnesses. In patients withshort RBC life spans, suppression can affect RBC counts more dramatically.These hypoplastic crises are usually transient and self-correcting beforeintervention is required. Aplastic crisis refers to a profound cessation of erythroid activity in patientswith chronic hemolytic anemias. It is associated with a rapidly falling hematocrit.Episodes are usually self-limited. Aplastic crises are caused by infection with aparticular strain of parvovirus, B19A. Children infected with this virus usuallydevelop permanent immunity. Aplastic crises do not often recur and are rarelyseen in adults. Management requires close monitoring of the hematocrit andreticulocyte count. If anemia becomes symptomatic, transfusion support isindicated. Most crises resolve spontaneously within 1–2 weeks. Further Readings Ataga KI, Orringa EP: Hypercoagulability in sickle cell disease: A curiousparadox. Am J Med 115:721, 2003 [PMID: 14693325] DeSimone J et al: Maintenance of elevated fetal hemoglobin levels bydecitabine during dose interval treatment of sickle cell anemia. Blood 99:3905,2002 [PMID: 12010787] Neufeld EJ: Oral chelators deferasirox and deferiprone for transfusionaliron overload in thalassemia major: New data, new questions. Blood 107:3436,2006 [PMID: 16627763] Quek L, Thein SL: Molecular therapies in beta-thalassaemia. Br J Haematol136:353, 2007 [PMID: 17129232] Steinberg MH: Pathophysiologically based drug treatment of sickle celldisease. Trends Pharmacol Sci 27:204, 2006 [PMID: 16530854] Switzer JA et al: Pathophysiology and treatment of stroke in sickle-celldisease: Present and future. Lancet Neurol 5:501, 2006 [PMID: 16713922] Ware RE et al: Predictors of fetal hemoglobin response in children withsickle cell anemia receiving hydroxyurea therapy. Blood 99:10, 2002 [PMID:11756146] Bibliography Benz EJ: Hemoglobin variants associated with hemolytic anemia, alteredoxygen affinity, and methemoglobinemias, in Hematology: Basic Principles andPractice, 3d ed, R Hoffman et al (eds). New York, Churchill Livingstone, 2000,pp 554–561 Clasta S, Vichinsky EP: Managing sickle cell disease. BMJ 327:1151,2003 Embury SH, Vichinsky EP: Sickle cell disease, in Hematology: BasicPrinciples and Practice, 3d ed, R Hoffman et al (eds). New York, ChurchillLivingstone, 2000, pp 510–554 Forget BG: Thalassemia syndromes, in Hematology: Basic Principles andPractice, 3d ed, R Hoffman et al (eds). New York, Churchill Livingstone, 2000,pp 485–510 Steinberg MH, Benz EJ Jr: Pathobiology of the human erythrocyte and itshemoglobins, in Hematology: Basic Principles and Practice, 3d ed, R Hoffman etal (eds). New York, Churchill Livingstone, 2000, pp 356–367