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PubMed This is a summary of 22 peer-reviewed journal articles Updated
Hematology · Pyruvate Kinase Deficiency

Treating PKD: From Supportive Care to Disease-Modifying Therapies

At a Glance

Treatment for Pyruvate Kinase Deficiency (PKD) ranges from supportive care like blood transfusions to disease-modifying therapies like Mitapivat. The right treatment depends on anemia severity, and all patients require lifelong monitoring for iron overload.

Treatment for Pyruvate Kinase Deficiency (PKD) has entered a new era. For decades, care was limited to managing symptoms through blood transfusions and surgery. Today, while these “supportive” treatments remain vital, new “disease-modifying” and curative options are changing the outlook for patients and families [1][2].

A Framework for Treatment Decisions

Treatment is generally tailored to the severity of the anemia and how it affects a patient’s daily life, rather than a single blood test number [3][4].

Severity Level Typical Presentation Primary Treatment Focus
Mild Anemia is present but the body compensates well. Monitoring for iron overload and gallstones [5].
Moderate Symptoms like fatigue or jaundice impact daily life; occasional transfusions needed during illness [3]. Supportive care, mitapivat (for adults), or considering splenectomy [6][1].
Severe Regular, lifelong transfusions are required to maintain growth and activity [7]. Intensive supportive care, mitapivat, splenectomy, or curative options like stem cell transplant [2][7].

Supportive Care: Managing the Anemia

The goal of supportive care is to ensure the body has enough healthy red blood cells to function.

  • Red Blood Cell Transfusions: These are “symptom-directed.” This means a transfusion is given based on how a patient feels (e.g., extreme fatigue, poor growth) rather than just because a hemoglobin number is low [3][4].
  • Splenectomy: Removing the spleen can help because the spleen is the primary site where PKD-affected red blood cells are destroyed [1].
    • Benefits: It often results in a significant increase in hemoglobin and may reduce or eliminate the need for transfusions [8][6].
    • Risks: The spleen is a vital part of the immune system. Removing it creates a lifelong risk of severe infections (sepsis), blood clots (thrombosis), and high blood pressure in the lungs (pulmonary hypertension) [9][10][11].

Disease-Modifying Therapy: Mitapivat (Pyrukynd)

Mitapivat is a first-in-class oral medication approved for adults with PKD [12][13].

  • How it works: It is an allosteric activator, meaning it “turns on” the pyruvate kinase enzyme, helping it work better even if it is mutated [14][15].
  • The result: By increasing the enzyme’s activity, the drug helps red blood cells produce more energy (ATP), which makes them live longer [16][17]. In clinical trials, many patients saw a sustained increase in hemoglobin and a reduced need for transfusions [18][2].
  • Monitoring: Like all medications, it requires monitoring for side effects, such as potential changes in hormone levels or liver enzymes, which your care team will track with routine blood work [19].

Curative Options: Stem Cell Transplant

An allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for PKD [7].

  • When it is considered: It is typically reserved for children or young adults with the most severe, transfusion-dependent forms of the disease [7][20].
  • How it works: The patient’s own blood-producing cells are replaced with healthy donor cells that produce normal pyruvate kinase.
  • Risks: While it can offer a “normal” life without anemia, it is a high-risk procedure that can lead to graft-versus-host disease (GVHD), where the donor cells attack the patient’s body, and other serious complications [21][22].

A Note on Iron Overload

Regardless of the treatment path, iron overload is a critical concern for all PKD patients. The body has no natural way to get rid of excess iron, which can build up from transfusions or simply because the body absorbs more iron when it is trying to make more red blood cells [5][19]. Monitoring iron levels in the liver and heart is a lifelong necessity [19].

Common questions in this guide

When is a splenectomy recommended for PKD?
A splenectomy may be considered for moderate to severe PKD to help increase hemoglobin levels and reduce the need for blood transfusions. However, removing the spleen carries lifelong risks, including serious infections and blood clots, which must be carefully managed.
What is Mitapivat (Pyrukynd) and how does it work?
Mitapivat is an oral medication approved for adults with PKD. It works by activating the mutated pyruvate kinase enzyme, helping red blood cells produce more energy so they live longer and improve anemia symptoms.
Can pyruvate kinase deficiency be cured?
Currently, the only potential cure for PKD is a stem cell transplant. This high-risk procedure replaces the patient's blood-producing cells with healthy donor cells, and is typically reserved for children or young adults with severe, transfusion-dependent PKD.
Why do I need to monitor my iron levels if I have PKD?
People with PKD are at a high risk for iron overload, even if they do not receive regular blood transfusions. The body absorbs extra iron when trying to produce more red blood cells, and excess iron can build up in the liver and heart over time.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my (or my child's) symptoms and growth, would you classify this case as transfusion-dependent or non-transfusion-dependent?
  2. 2.Is a splenectomy appropriate at this stage, and what specific steps will we take to manage the lifelong risk of infection and blood clots afterward?
  3. 3.Am I a candidate for mitapivat, and how will we monitor its effect on my hemoglobin and iron levels?
  4. 4.What are the criteria you use to determine if a stem cell transplant is necessary, and what are the specific risks for a patient with PKD?
  5. 5.How often should we be checking for iron overload, even if I am not receiving regular transfusions?

Questions For You

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References

References (22)
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    Prevalence and management of iron overload in pyruvate kinase deficiency: report from the Pyruvate Kinase Deficiency Natural History Study.

    van Beers EJ, van Straaten S, Morton DH, et al.

    Haematologica 2019; (104(2)):e51-e53 doi:10.3324/haematol.2018.196295.

    PMID: 30213831
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    Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial.

    Glenthøj A, van Beers EJ, Al-Samkari H, et al.

    The Lancet. Haematology 2022; (9(10)):e724-e732 doi:10.1016/S2352-3026(22)00214-9.

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    The variable manifestations of disease in pyruvate kinase deficiency and their management.

    Al-Samkari H, Van Beers EJ, Kuo KHM, et al.

    Haematologica 2020; (105(9)):2229-2239 doi:10.3324/haematol.2019.240846.

    PMID: 33054048
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    Pyruvate Kinase Deficiency: Current Challenges and Future Prospects.

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    Mitapivat: A Quinolone Sulfonamide to Manage Hemolytic Anemia in Adults With Pyruvate Kinase Deficiency.

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    American journal of therapeutics 2023; (30(5)):e433-e438 doi:10.1097/MJT.0000000000001663.

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    Case report: Modified transplantation for pediatric patients with pyruvate kinase deficiency.

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    Evaluation of the risk factors for venous thromboembolism post splenectomy - A ten year retrospective cohort study in St James's hospital.

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    Paravertebral Mass and Diffuse Lymphadenopathy in a Patient with Pyruvate Kinase Deficiency: Malignancy or Alternative Etiology?

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    Pyruvate kinase activator: A major breakthrough in the world of Hematology.

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    AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency.

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    AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes.

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    Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in sickle cell disease: A phase 2, open-label study.

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This information about PKD treatments is for educational purposes only. Always consult your hematologist to determine the safest and most effective care plan for your specific case.

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