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Investigating Anemia and the Possibility of Pyruvate Kinase Deficiency: What Is Your Next Step?

  • Authors: Hanny Al-Samkari, MD
  • CME / ABIM MOC Released: 3/21/2023
  • Valid for credit through: 3/21/2024
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  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for benign hematologists and other physicians who see patients with PKD.

The goal of this activity is for learners to be better able to diagnose and manage PKD according to the latest evidence.

Upon completion of this activity, participants will:

  • Have greater competence related to
    • Diagnosing PKD
    • Implementing an appropriate treatment approach for PKD
    • Managing adverse events associated with PKD treatment approaches
  • Demonstrate greater confidence in their ability to
    • Implement new treatment approaches for the management of PKD


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  • Hanny Al-Samkari, MD

    Massachusetts General Hospital
    Harvard Medical School
    Boston, Massachusetts


    Hanny Al-Samkari, MD, has the following relevant financial relationships:
    Consultant or advisor for: Agios Pharmaceuticals, Inc.; argenx; Forma; Moderna, Inc.; Novartis Pharmaceuticals Corporation; Rigel; Swedish Orphan Biovitrum
    Research funding from: Agios Pharmaceuticals, Inc.; Amgen, Inc.; SOBI; Vaderis


  • Sanneke Koekkoek

    Medical Education Director, WebMD Global, LLC


    Sanneke Koekkoek has no relevant financial relationships.

  • Jason Luis Quiñones, PhD

    Associate Medical Writer, Medscape, LLC


    Jason Luis Quiñones, PhD, has no relevant financial relationships.

Compliance Reviewer

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Stephanie Corder, ND, RN, CHCP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.

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Investigating Anemia and the Possibility of Pyruvate Kinase Deficiency: What Is Your Next Step?

Authors: Hanny Al-Samkari, MDFaculty and Disclosures

CME / ABIM MOC Released: 3/21/2023

Valid for credit through: 3/21/2024


The following cases are modeled on the interactive grand rounds approach. The questions within the activity are designed to test your current knowledge. After each question, you will be able to see whether you answered correctly and read evidence-based information that supports the most appropriate answer choice. The questions are designed to challenge you; you will not be penalized for answering the questions incorrectly. At the end of the activity, there will be a short post-test assessment based on the material presented.

Case 1: Adult patient with newly diagnosed pyruvate kinase deficiency (PKD)


John is a 25-year-old male patient who presents to the clinic to establish care for his diagnosis of autoimmune hemolytic anemia, which was diagnosed in early childhood. During childhood, he suffered from jaundice that caused him to be bullied in school, and he was unable to participate in sports due to poor exercise tolerance. In adulthood, this has resulted in reduced health-related quality of life (HRQoL), including jaundice that negatively affects his romantic relationships and self-confidence. His reduced ability to concentrate and fatigue has caused challenges in making it through a full 8-hour workday. John’s medical history includes direct Coombs testing, which was negative on 3 separate occasions. In addition, he is noted as being poorly responsive to corticosteroid therapy and unresponsive to prednisone. Given the inconsistency of this history with autoimmune hemolysis, you perform a hemolytic anemia workup.

Table 1. John's Initial Workup and Laboratory Testing

Patient information
  • 25 years old, male
  • Height: 5' 8"
  • Weight: 140 lb
  • BMI: 21.3
Personal and family medical history
  • No family history of a hemolytic or blood disorder
  • "Poor response" to corticosteroids and no response to rituximab
  • Has received daily oral folate supplementation and intermittent blood transfusions
Physical exam
  • Signs and symptoms:
    • Chronic jaundice
    • Fatigue
    • Reduced activity
    • Difficulty concentrating/brain fog
Laboratory evaluations
  • Lab results:
    • Hb levels: 8.5 g/dL (historical range: 7.5-9 g/dL)
    • WBC and platelets: normal
    • Mean corpuscular volume: 101 fL
    • Reticulocyte count: 20%
    • Bilirubin: 4.4 mg/dL (indirect, 3.8 mg/dL)
    • LDH: 450 IU/L
    • Haptoglobin: undetectable
  • Etiology-specific testing:
    • Peripheral blood film: No spherocytes, stomatocytes, or elliptocytes; no fragment cells, no red cell agglutination
    • Occasional crenated echinocytes
    • Increased polychromasia
    • Platelets and white cells unremarkable
    • Folate, B12 levels: normal
    • Hemoglobin electrophoresis: normal
    • Direct Coombs test: negative
    • Cold agglutinins: negative
    • G6PD enzyme activity: normal
    • Osmotic fragility testing: normal
    • Flow cytometry for CD55 and CD59: unremarkable
    • PK enzyme activity: low (2.4 U/g Hb, reference range 5.5-12.4 U/g Hb
BMI, body-mass index; CD, cluster of differentiation; Hb, hemoglobin; LDH, lactate dehydrogenase; PK, pyruvate kinase; WBC, white blood cell.
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