ASH Clinical News ACN_5.7_Digital | Page 15

You Make the Call: Readers’ Response d through the Consult e program a Colleagu month’s clinical to next question submitte in your response e the Call we pick a challenging clinical do. Send You Mak what you would print issue. the Call,” want to know next “You Make y. in in the , but we also Each month G6PD deficienc up to the expert’s expert’s response patient with answer matches and post the of gout in a treatment see how your discusses the dilemma and Datta, MD, Yvonne H. This month, (World Health (G6PD) deficiency to prolonged cy secondary e-dehydrogenase rate is 27. renal insufficien r filtration glucose-6-phosphat y, and chronic patient with and his glomerula and a platelet count ld male Samoan s gouty arthropath is 2.67 mg/dL 35.1 percent, disabled I have a 36-year-o III), chronic tophaceou His baseline creatinine hematocrit level of y and has been class use. g/dL, to gouty arthropath Organization matory drug level of 11.6 anti-inflam hemoglobin difficulty walking due known nonsteroidal blood count of 13.8, which is a pain and painful ific enzyme, ing extreme He has a white his extensive, uric acid–spec 9 /L. He is experienc e, a pegylated to try this agent to reduce setting with of 438×10 wants e in a hospital institute pegloticas The patient . pegloticas for eight years. logist would like to ring deficiency His rheumato in patients with G6PD the possibility of administe about cause of hemolysis for other opinions should occur. looking hemolysis tophi. I am brisk support if transfusion ma: Clinical Dilem Colleague Consult a ASH Through is a service for ASH the exchange Consult a Colleague helps facilitate gists members that between hematolo on can of informati ASH members from and their peers. ion on clinical cases seek consultat in 11 categories: qualified experts inion Expert Op • Anemias oietic cell • Hematop transplantation inopathies • Hemoglob osis is/thromb • Hemostas Datta, MD Yvonne H.   Medicine Fellowship Professor of tation /Oncology ematology and Transplan Director, H Oncology, Hematology, Division of a of Minnesot University setting of newly in the acute without rasburicase lymphoma The use of leukemia or . In that rasbur- high grade l as pegylated may be warranted diagnosed also known G6PD testing advised in case additiona (Krystexxa), severe refractory waiting for the patient for use in Pegloticase testing is still half-life in this case, and has a been approved event, G6PD later. However, The use of peglot- icase, has two weeks es uric acid infused every doses are needed G6PD deficiency. con- se metaboliz gout. It is harm. The with to have days. Rasburica cause serious uric acid levels se is known ns. Severe of 10 to 12 patient may transfusio lowering serum byproduct of rasburica icase in this may need . A acute kidney into allantoin, stress. just that he hyperkalemia, kidney crystal formation can cause oxidative cern is not can cause decreased pathway peroxide, which phosphate acute hemolysis This patient has chronic injury. pentose is hydrogen kidney the shock. risk for also generates enzyme in injury, and him at greater e-induced hemolysis G6PD is an pentose and G6PD glucose to C for disease, placing oxidative stress. that converts case of pegloticas eresis, and vitamin protects against ity of varying sever- One reported plasmaph n, prolonged NADPH, which X-linked abnormal are exposed is an required transfusio reported case required half-life of the when red cells one, deficiency Another in hemolysis Patients such as this to the long recovery.² ity that results possibly related stress. .³ In the setting normal hemolysis e t oxidative to 60% of hemodialysis, of to significan , have 10% e causing ongoing harms of pegloticas case reports III deficiency pegloticas , the potential been several with type when There have globinemia of G6PD deficiency G6PD activity. potential benefits. and methemo used in patients hemolysis outweigh the significant e have been this phate or pegloticas , even when of glucose-6-phos deficiency rasburicase implications REFERENCES the hemolysis ized G6PD and drug therapy In some cases, methylene with unrecogn Tichy EM. Review J Health Syst Pharm. 2018;75:97-104. following 1. Belfield KD, given has been mild. and haemolysis deficiency. Am was naemia deficiency dehydrogenase negative glucose-6- when the patient ia, resulting in some Xu JZ, et al. Methaemoglobi with a falsely lla L, Sung D, for was worsened gout in a patient (Oxford). 2014;53:2310-1. 2. Geraldino-Pardi for refractory Rheumatology methemoglobinem to a boxed warning pegloticase infusion Am J Ther. 2018; deficiency result. led blue for the for ociated hemolysis. reports have screening phosphate dehydrogenase These Pegloticase-ass which ZY. e, in Y, Bhat deaths. Osman-Malik and pegloticas nded and use in patients 3. Minshar MA, rasburicase is recomme PMID: 30211701. ed.¹ G6PD deficiency deficiency is discourag pegloticase. G6PD using with known I advise against In this patient, as • Lymphom disorders roliferative • Lymphop s • Leukemia Waldenström myeloma & • Multiple ulinemia macroglob s liferative neoplasm • Myelopro s plastic syndrome • Myelodys ytopenias Thromboc • es”) will s (“colleagu Assigned volunteer within two business inquiries respond to phone). by email or days (either dilemma? clinical Have a puzzling and read more s at volunteer Submit a question, a Colleague onsult.aspx about Consult nicians/C hematology.org/Cli QR code. or scan the to a a request related here, * If you have not listed c disorder ation to hematologi your recommend so it can be .org please email hematology ashconsult@ addition in the future. for considered marrow and bone a: for FANCA) started on heterozygous s and was ’s Clinical Dilemm compound -severe cytopenia have physical stigmata anemia (FA; Next Month with moderate with Fanconi does not d not recommen , : ASH does tests, physicians any specific and or endorse , or opinions, or products, procedures tion, warranty, representa any disclaims any Reliance on to the same. is solely guaranty as in this article n provided informatio risk. at your own DISCLAIMER 2018 ag. She in October ld female patient and eltrombop found two I have a 21-year-o X syndrome. She presented November 2018) . We recently triple factor (until ietic cell be dwindling failure, 46, hematopo appears to colony-stimulating her response to take her for allogeneic a stem cell granulocyte y well, but . for alloHCT, I and intend of the diagnosis d to treatment reasonabl optimal timing or other) for alloHCT? matched siblings) advise me on the G+TBI She responde donors (she has no Could you TG or Flu/Cy/AT prognosis. soon as possible. conditioning (Flu/Cy/A matched unrelated ent and overall (alloHCT) as of managem blood) and transplantation FA in terms peripheral ● marrow vs. interacts with [email protected]. source (bone X syndrome how triple us at ashclinica am not sure you respond? Email How would 40 ASH Clinical June 2019 News We asked, and you answered! Here are a few responses from this month’s “You Make the Call.” To see how the expert responded, turn to page 40. Clinical Dilemma: I have a 36-year-old male Samoan patient with glucose-6-phosphate- dehydrogenase (G6PD) deficiency (World Health Organization class III), chronic tophaceous gouty arthropa- thy, and chronic renal insufficiency secondary to prolonged nonsteroidal anti-inflammatory drug use. His baseline creatinine is 2.67 mg/dL and his glomerular filtration rate is 27. He has a white blood count of 13.8, hemoglobin level of 11.6 g/ dL, hematocrit level of 35.1%, and a platelet count of 438×10 9 /L. He is experiencing extreme pain and difficulty walking due to gouty ar- thropathy and has been disabled for eight years. His rheumatologist would like to institute pegloticase, a pegylated uric acid–specific enzyme, which is a known cause of hemolysis in patients with G6PD deficiency. The patient wants to try this agent to reduce his extensive, painful tophi. I am looking for other opinions about the possibility of administering pegloticase in a hospital setting with transfusion support if brisk hemolysis should occur. An initial erythrocytapheresis to reduce G6PD-deficient red blood cells and administration of pegloticase may work. One can give the latter every four weeks either with or without erythrocytapheresis, depending on the degree of subsequent hemolysis and response to the drug. Susumu Inoue, MD Hurley Children’s Hospital Flint, MI Try pulse corticosteroid therapy at 50 mg once weekly. Taper with improve- ment and treat side effects, such as diabetes, if needed. Or try dexametha- sone 20 mg once weekly. Treat side effects, such as hyperglycemia, as needed. Herbert Goldman, MD San Juan, Puerto Rico I have considerable experience with G6PD deficiency hemolysis, having been part of the group led by Alf Alving, MD, who discovered and characterized this genetic disease. Since all known G6PD mutations cause a loss of G6PD activity as the red cells age, the youngest group of cells in the circulation are resistant to hemolysis. A good strategy for this patient would be to start with a reduced dose of the hemolytic drug, say 25% of the known hemolytic dose, for two weeks. During this time, mild hemolysis would occur but reticulocytosis would allow maintaining only a mild anemia. Recovery to normal hemoglobin levels would ensue, as this is a compensated hemolytic anemia state. Then repeat the process with a higher dose, say 50% of the hemolytic dose, for another two weeks. After the anemia is compensated, increase to the full dose. It should be George J. Brewer, MD University of Michigan Ann Arbor, MI See more reader responses at ashclinicalnews.org/ you-make-the-call. Know PK Deficiency Would You Identify this Underrecognized Cause of Hemolytic Anemia? Pyruvate kinase (PK) deficiency may be underrecognized, 1 but should be considered in patients with hemolysis who lack evidence of an acquired immune disorder. 1,2 Patients with PK deficiency may experience: • Chronic hemolytic anemia • Iron overload even without transfusions • Gallstones, splenomegaly, jaundice Learn more about ongoing clinical trials at www.ActivateClinicalTrials.com Diagnostic Testing Program New Testing Program* Diagnostic testing is now available from ARUP Laboratories — at no cost to the patient. Find out more online at www.knowpkdeficiency.com/testing * While Agios provides financial support for this program, all tests and services are performed by the selected third- party. Agios receives contact information for healthcare professionals who submit tests under this program and limited de-identified aggregate data. 1. Grace RF, et al. Am J Hematol. 2015;90(9):825-30. 2. Hirono A, et al. Chapter 182 Pyruvate Kinase Deficiency and Other Enzymopathies of the Erythrocyte. New York, NY: McGraw Hill. 2014. ©2019 Agios Pharmaceuticals, Inc. All rights reserved. PKD-ALL-0051 ASHClinicalNews.org possible to give the drug indefinitely, recognizing that the patient is in a chronic compensated hemolytic state. Patient identification and diagnosis are taking on new importance.