TY - JOUR
T1 - Clinical spectrum of pyruvate kinase deficiency
T2 - Data from the pyruvate kinase deficiency natural history study
AU - Grace, Rachael F.
AU - Bianchi, Paola
AU - van Beers, Eduard J.
AU - Eber, Stefan W.
AU - Glader, Bertil
AU - Yaish, Hassan M.
AU - Despotovic, Jenny M.
AU - Rothman, Jennifer A.
AU - Sharma, Mukta
AU - McNaull, Melissa M.
AU - Fermo, Elisa
AU - Lezon-Geyda, Kimberly
AU - Morton, D. Holmes
AU - Neufeld, Ellis J.
AU - Chonat, Satheesh
AU - Kollmar, Nina
AU - Knoll, Christine M.
AU - Kuo, Kevin
AU - Kwiatkowski, Janet L.
AU - Pospíšilová, Dagmar
AU - Pastore, Yves D.
AU - Thompson, Alexis A
AU - Newburger, Peter E.
AU - Ravindranath, Yaddanapudi
AU - Wang, Winfred C.
AU - Wlodarski, Marcin W.
AU - Wang, Heng
AU - Holzhauer, Susanne
AU - Breakey, Vicky R.
AU - Kunz, Joachim
AU - Sheth, Sujit
AU - Rose, Melissa J.
AU - Bradeen, Heather A.
AU - Neu, Nolan
AU - Guo, Dongjing
AU - Al-Sayegh, Hasan
AU - London, Wendy B.
AU - Gallagher, Patrick G.
AU - Zanella, Alberto
AU - Barcellini, Wilma
N1 - Funding Information:
The Pyruvate Kinase Deficiency Natural History Study was supported by research funding from Agios Pharmaceuticals.
Funding Information:
The authors acknowledge all the patients with pyruvate kinase deficiency who contributed to this Natural History Study data and Anran Li for her assistance with statistical analysis. The Pyruvate Kinase Deficiency Natural History Study was supported by research funding from Agios Pharmaceuticals.
Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/5/17
Y1 - 2018/5/17
N2 - An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P 5 .007), lower indirect bilirubin (P 5 .005), and missense PKLR mutations (P 5 .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.
AB - An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment for 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia that required transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%), and many were treated with exchange transfusions (46%). Children age 5 years and younger were often transfused until splenectomy. Splenectomy (150 [59%] of 254 patients) was associated with a median increase in hemoglobin of 1.6 g/dL and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin (P 5 .007), lower indirect bilirubin (P 5 .005), and missense PKLR mutations (P 5 .0017). Postsplenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%), but other complications such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, postsplenectomy sepsis, pulmonary hypertension, and leg ulcers were not uncommon. Overall, 87 (34%) of 254 patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin. This trial was registered at www.clinicaltrials.gov as #NCT02053480.
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U2 - 10.1182/blood-2017-10-810796
DO - 10.1182/blood-2017-10-810796
M3 - Article
C2 - 29549173
AN - SCOPUS:85047251873
SN - 0006-4971
VL - 131
SP - 2183
EP - 2192
JO - Blood
JF - Blood
IS - 20
ER -
