Pediatric Clinics of North America - CIPERJ

More documents

Recommendations

Info

Pediatr Clin N Am 55 (2008) 483–501 Hydroxyurea for Children with Sickle Cell Disease Matthew M. Heeney, MD a,b, *, Russell E. Ware, MD, PhD c a Harvard Medical School, Boston, MA, USA b Division of Hematology/Oncology, Children’s Hospital Boston, Fegan 704, 300 Longwood Avenue, Boston, MA 02115, USA c Department of Hematology, St. Jude Children’s Research Hospital, 332 North Lauderdale, MS 355, Memphis, TN 38105, USA Sickle cell disease (SCD) refers to a group of genetic hemolytic anemias in which the erythrocytes have a predominance of sickle hemoglobin (HbS) due to inheritance of a b-globin mutation (b S ). The b S mutation is the result of a single amino acid substitution (HbS, HBB Glu6Val) in the b-globin of the hemoglobin heterotetramer, thus forming HbS. Affected individuals typically are homozygous for the sickle mutation (HbSS) or have a compound heterozygous state (eg, HbSC, HbS b-thalassemia). The b S mutation creates a hydrophobic region that, in the deoxygenated state, facilitates a noncovalent polymerization of HbS molecules that damages the erythrocyte membrane and changes the rheology of the erythrocyte in circulation, causing hemolytic anemia, vaso-occlusion, and vascular endothelial dysfunction. SCD is the most common inherited hemolytic anemia in the United States. Approximately 70,000 to 100,000 individuals in the United States are affected, most commonly those who have ancestry from Africa, the Indian subcontinent, the Arabian Peninsula, or the Mediterranean Basin. Worldwide, millions of persons are affected with SCD, especially in regions with endemic malaria, such as Africa, the Middle East, and India. SCD is characterized by a lifelong hemolytic anemia with an ongoing risk for acute Dr. Heeney is supported by NIH K12 HL087164 and U54 HL070819. Dr. Ware is supported by U54 HL070590, U01 HL078787, N01 HB 07155, and American Syrian Lebanese Associated Charities. * Corresponding author. Division of Hematology/Oncology, Department of Medicine, Children’s Hospital, Boston, Fegan 704, 300 Longwood Avenue, Boston, MA 02115. E-mail address: matthew.heeney@childrens.harvard.edu (M.M. Heeney). 0031-3955/08/$ - see front matter Ó 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.pcl.2008.02.003 pediatric.theclinics.com
484 HEENEY & WARE medical complications and inexorable accrual of organ damage in most affected individuals. There is wide variability in the phenotypic severity of SCD that is not well understood. This variation can be explained partly by differences in the total hemoglobin concentration, the mean corpuscular hemoglobin concentration, erythrocyte rheology, the percentage of adhesive cells, the proportion of dense cells, the presence or absence of a-thalassemia, and the b-globin haplotype [1–5]. The percentage of fetal hemoglobin (HbF), however, is perhaps the most important laboratory parameter influencing clinical severity in SCD [6,7]. In unaffected individuals, HbF comprises only 5% of the total hemoglobin by age 3 to 6 months and falls to below 1% in adults [8]. In contrast, patients with SCD typically have HbF levels ranging from 1% to 20% [9] and those with genetic mutations leading to hereditary persistence of HbF (HPFH) can have HbF levels that reach 30% to 40% of the total hemoglobin [10]. Based on the observation that infants with SCD have few complications early in life, it was hypothesized that HbF, the predominant hemoglobin in fetal and infant stages of life, might ameliorate the phenotypic expression of SCD [11]. In addition, compound heterozygotes for the sickle mutation and HPFH are relatively protected from severe clinical symptoms [12]. Subsequently, it was shown that increased HbF percentage is associated with decreased clinical severity in SCD, using endpoints, such as the number of vaso-occlusive painful events, transfusions, and hospitalizations [1,13]. HbF does not, however, seem to protect from some complications [14], perhaps because the HbF levels were inadequate to provide protection [3,15]. A potential threshold of 20% HbF is suggested, above which patients experience fewer clinical events [16]. The % HbF also has emerged as the most important predictor of early mortality in patients with SCD [6,17]. Although the genetic and molecular pathophysiology of SCD are well described and understood in considerable detail, there has been disappointing progress toward definitive, curative therapy. Bone marrow transplantation offers a cure but currently requires an HLA-matched sibling donor for best results. This requirement limits the number of patients who can benefit from this approach. Moreover, even using a matched sibling donor, bone marrow transplantation remains associated with considerable morbidity (primarily graft-versus-host disease) and low, but not negligible, mortality. In lieu of curative therapy, one approach given considerable effort over the past 25 years has been the pharmacologic induction of HbF beyond the fetal and newborn period. Several pharmacologic agents have shown promise, including demethylating agents, such as 5-azacytidine [18] and decitabine [19–21], and short-chain fatty acids, such as butyrate [22–25], but each has limitations in route of administration, safety, or sustained efficacy. Hydroxyurea, in contrast, has a long and growing track record in inducing HbF in patients with SCD. In addition, hydroxyurea has a variety of
Page 2 and 3:
Pediatr Clin N Am 55 (2008) xiii-xi
Page 4 and 5:
Pediatr Clin N Am 55 (2008) 287-304
Page 6 and 7:
DECISION ANALYSIS IN PEDIATRIC HEMA
Page 8 and 9:
Page 10 and 11:
Page 12 and 13:
Page 14 and 15:
Page 16 and 17:
Nietert et al [30] Treatment of sic
Page 18 and 19:
Page 20 and 21:
Page 22 and 23:
Page 24 and 25:
VENOUS THROMBOEMBOLISM IN CHILDREN
Page 26 and 27:
Page 28 and 29:
Page 30 and 31:
Page 32 and 33:
Page 34 and 35:
Page 36 and 37:
Page 38 and 39:
Page 40 and 41:
Page 42 and 43:
PEDIATRIC ARTERIAL ISCHEMIC STROKE
Page 44 and 45:
Page 46 and 47:
Page 48 and 49:
Page 50 and 51:
Page 52 and 53:
Page 54 and 55:
Page 56 and 57:
Page 58 and 59:
CARE OF PATIENTS WITH VASCULAR ANOM
Page 60 and 61:
Page 62 and 63:
Page 64 and 65:
Page 66 and 67:
Page 68 and 69:
Page 70 and 71:
Page 72 and 73:
Page 74 and 75:
358 RODRIGUEZ & HOOTS Fig. 1. X-lin
Page 76 and 77:
Table 1 Clotting factor concentrate
Page 78 and 79:
Table 1 (continued ) Factor VIII (o
Page 80 and 81:
364 RODRIGUEZ & HOOTS was administe
Page 82 and 83:
366 RODRIGUEZ & HOOTS Antifibrinoly
Page 84 and 85:
368 RODRIGUEZ & HOOTS infections an
Page 86 and 87:
370 RODRIGUEZ & HOOTS Fig. 3. Schem
Page 88 and 89:
372 RODRIGUEZ & HOOTS protein is no
Page 90 and 91:
374 RODRIGUEZ & HOOTS [2] Berntorp
Page 92 and 93:
376 RODRIGUEZ & HOOTS [42] Carcao M
Page 94 and 95:
378 ROBERTSON et al von Willebrand
Page 96 and 97:
380 ROBERTSON et al Fig. 2. A propo
Page 98 and 99:
382 ROBERTSON et al a heterogenous
Page 100 and 101:
384 ROBERTSON et al of considering
Page 102 and 103:
386 ROBERTSON et al Type 2M Type 2M
Page 104 and 105:
388 ROBERTSON et al Desmopressin is
Page 106 and 107:
390 ROBERTSON et al References [1]
Page 108 and 109:
392 ROBERTSON et al [46] Nesbitt IM
Page 110 and 111:
394 BLANCHETTE & BOLTON-MAGGS A key
Page 112 and 113:
396 BLANCHETTE & BOLTON-MAGGS recep
Page 114 and 115:
398 BLANCHETTE & BOLTON-MAGGS and p
Page 116 and 117:
400 BLANCHETTE & BOLTON-MAGGS Fig.
Page 118 and 119:
402 BLANCHETTE & BOLTON-MAGGS in di
Page 120 and 121:
404 BLANCHETTE & BOLTON-MAGGS the s
Page 122 and 123:
406 BLANCHETTE & BOLTON-MAGGS findi
Page 124 and 125:
408 BLANCHETTE & BOLTON-MAGGS as a
Page 126 and 127:
410 BLANCHETTE & BOLTON-MAGGS splen
Page 128 and 129:
412 BLANCHETTE & BOLTON-MAGGS with
Page 130 and 131:
414 BLANCHETTE & BOLTON-MAGGS react
Page 132 and 133:
416 BLANCHETTE & BOLTON-MAGGS [16]
Page 134 and 135:
Page 136 and 137:
Page 138 and 139:
422 FASANO & LUBAN of storage and t
Page 140 and 141:
424 FASANO & LUBAN Leukocyte reduct
Page 142 and 143:
426 FASANO & LUBAN RBCs is decrease
Page 144 and 145:
Table 1 Blood component characteris
Page 146 and 147:
430 FASANO & LUBAN Alloimmunization
Page 148 and 149: 432 FASANO & LUBAN of individual un
Page 150 and 151: 434 FASANO & LUBAN patients have an
Page 152 and 153: 436 FASANO & LUBAN adults; therefor
Page 154 and 155: 438 FASANO & LUBAN [21]. Meta-analy
Page 156 and 157: 440 FASANO & LUBAN Pretransfusion m
Page 158 and 159: 442 FASANO & LUBAN [55,56]. This is
Page 160 and 161: 444 FASANO & LUBAN [20] Roseff SD,
Page 162 and 163: Pediatr Clin N Am 55 (2008) 447-460
Page 164 and 165: THALASSEMIA UPDATE 449 hypochromia
Page 166 and 167: THALASSEMIA UPDATE 451 Fig. 1. Chan
Page 168 and 169: THALASSEMIA UPDATE 453 delivery of
Page 170 and 171: THALASSEMIA UPDATE 455 thromboses i
Page 172 and 173: THALASSEMIA UPDATE 457 On the basis
Page 174 and 175: THALASSEMIA UPDATE 459 [31] Kan YW,
Page 176 and 177: Pediatr Clin N Am 55 (2008) 461-482
Page 178 and 179: ORAL IRON CHELATORS 463 large iron-
Page 180 and 181: ORAL IRON CHELATORS 465 of 50 child
Page 182 and 183: ORAL IRON CHELATORS 467 Table 2 Com
Page 184 and 185: ORAL IRON CHELATORS 469 use in Nort
Page 186 and 187: ORAL IRON CHELATORS 471 needed to d
Page 188 and 189: ORAL IRON CHELATORS 473 in liver fi
Page 190 and 191: ORAL IRON CHELATORS 475 in the lowe
Page 192 and 193: ORAL IRON CHELATORS 477 Other oral
Page 194 and 195: ORAL IRON CHELATORS 479 [12] Borgna
Page 196 and 197: ORAL IRON CHELATORS 481 [55] Wonke
Page 200 and 201: HYDROXYUREA FOR CHILDREN WITH SICKL
Page 208 and 209: Fig. 1. Guideline for initiating, m
Page 218 and 219: 504 TRACY & RICE congenital spheroc
Page 220 and 221: 506 TRACY & RICE and antibodies aga
Page 222 and 223: 508 TRACY & RICE limited splenic vo
Page 224 and 225: 510 TRACY & RICE constitutes the pi
Page 226 and 227: 512 TRACY & RICE German experience
Page 228 and 229: 514 TRACY & RICE Table 1 Effect of
Page 230 and 231: 516 TRACY & RICE decreased bilirubi
Page 232 and 233: 518 TRACY & RICE [13] Bader-Meunier
show all

Pediatric Clinics of North America - CIPERJ

Create successful ePaper yourself

Delete template?

Save as template?