Clinical spectrum of pyruvate kinase deficiency: Data from the pyruvate kinase deficiency natural history study

Rachael F. Grace, Paola Bianchi, Eduard J. van Beers, Stefan W. Eber, Bertil Glader, Hassan M. Yaish, Jenny M. Despotovic, Jennifer A. Rothman, Mukta Sharma, Melissa M. McNaull, Elisa Fermo, Kimberly Lezon-Geyda, D. Holmes Morton, Ellis J. Neufeld, Satheesh Chonat, Nina Kollmar, Christine M. Knoll, Kevin Kuo, Janet L. Kwiatkowski, Dagmar PospíšilováYves D. Pastore, Alexis A. Thompson, Peter E. Newburger, Yaddanapudi Ravindranath, Winfred C. Wang, Marcin W. Wlodarski, Heng Wang, Susanne Holzhauer, Vicky R. Breakey, Joachim Kunz, Sujit Sheth, Melissa J. Rose, Heather A. Bradeen, Nolan Neu, Dongjing Guo, Hasan Al-Sayegh, Wendy B. London, Patrick G. Gallagher, Alberto Zanella, Wilma Barcellini

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2183-2192
Number of pages10
JournalBlood
Volume131
Issue number20
DOIs
Publication statusPublished - May 17 2018

Fingerprint

Pyruvate Kinase
Natural History
Splenectomy
Hemoglobins
Cholecystectomy
Iron
Iron Overload
Gallstones
Bilirubin
Congenital Nonspherocytic Hemolytic Anemia
Anemia
Bone
Congenital Hemolytic Anemia
Extramedullary Hematopoiesis
Defects
Leg Ulcer
Hyperbilirubinemia
Phototherapy
Pyruvate Kinase Deficiency of Red Cells
Monitoring

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Clinical spectrum of pyruvate kinase deficiency : Data from the pyruvate kinase deficiency natural history study. / Grace, Rachael F.; Bianchi, Paola; van Beers, Eduard J.; Eber, Stefan W.; Glader, Bertil; Yaish, Hassan M.; Despotovic, Jenny M.; Rothman, Jennifer A.; Sharma, Mukta; McNaull, Melissa M.; Fermo, Elisa; Lezon-Geyda, Kimberly; Morton, D. Holmes; Neufeld, Ellis J.; Chonat, Satheesh; Kollmar, Nina; Knoll, Christine M.; Kuo, Kevin; Kwiatkowski, Janet L.; Pospíšilová, Dagmar; Pastore, Yves D.; Thompson, Alexis A.; Newburger, Peter E.; Ravindranath, Yaddanapudi; Wang, Winfred C.; Wlodarski, Marcin W.; Wang, Heng; Holzhauer, Susanne; Breakey, Vicky R.; Kunz, Joachim; Sheth, Sujit; Rose, Melissa J.; Bradeen, Heather A.; Neu, Nolan; Guo, Dongjing; Al-Sayegh, Hasan; London, Wendy B.; Gallagher, Patrick G.; Zanella, Alberto; Barcellini, Wilma.

In: Blood, Vol. 131, No. 20, 17.05.2018, p. 2183-2192.

Research output: Contribution to journalArticle

Grace, RF, Bianchi, P, van Beers, EJ, Eber, SW, Glader, B, Yaish, HM, Despotovic, JM, Rothman, JA, Sharma, M, McNaull, MM, Fermo, E, Lezon-Geyda, K, Morton, DH, Neufeld, EJ, Chonat, S, Kollmar, N, Knoll, CM, Kuo, K, Kwiatkowski, JL, Pospíšilová, D, Pastore, YD, Thompson, AA, Newburger, PE, Ravindranath, Y, Wang, WC, Wlodarski, MW, Wang, H, Holzhauer, S, Breakey, VR, Kunz, J, Sheth, S, Rose, MJ, Bradeen, HA, Neu, N, Guo, D, Al-Sayegh, H, London, WB, Gallagher, PG, Zanella, A & Barcellini, W 2018, 'Clinical spectrum of pyruvate kinase deficiency: Data from the pyruvate kinase deficiency natural history study', Blood, vol. 131, no. 20, pp. 2183-2192. https://doi.org/10.1182/blood-2017-10-810796
Grace, Rachael F. ; Bianchi, Paola ; van Beers, Eduard J. ; Eber, Stefan W. ; Glader, Bertil ; Yaish, Hassan M. ; Despotovic, Jenny M. ; Rothman, Jennifer A. ; Sharma, Mukta ; McNaull, Melissa M. ; Fermo, Elisa ; Lezon-Geyda, Kimberly ; Morton, D. Holmes ; Neufeld, Ellis J. ; Chonat, Satheesh ; Kollmar, Nina ; Knoll, Christine M. ; Kuo, Kevin ; Kwiatkowski, Janet L. ; Pospíšilová, Dagmar ; Pastore, Yves D. ; Thompson, Alexis A. ; Newburger, Peter E. ; Ravindranath, Yaddanapudi ; Wang, Winfred C. ; Wlodarski, Marcin W. ; Wang, Heng ; Holzhauer, Susanne ; Breakey, Vicky R. ; Kunz, Joachim ; Sheth, Sujit ; Rose, Melissa J. ; Bradeen, Heather A. ; Neu, Nolan ; Guo, Dongjing ; Al-Sayegh, Hasan ; London, Wendy B. ; Gallagher, Patrick G. ; Zanella, Alberto ; Barcellini, Wilma. / Clinical spectrum of pyruvate kinase deficiency : Data from the pyruvate kinase deficiency natural history study. In: Blood. 2018 ; Vol. 131, No. 20. pp. 2183-2192.
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abstract = "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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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

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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