eMedicine Specialties > Pediatrics: General Medicine > Hematology
Pyruvate Kinase Deficiency: Treatment & Medication
Updated: Oct 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Extremely severe fetal anemia associated with hydrops fetalis usually requires intrauterine transfusion. Phototherapy or exchange transfusion is usually required for severe hyperbilirubinemia in the newborn. Simple blood transfusion is administered for anemia during early childhood and, occasionally, into adulthood.
- In older patients with pyruvate kinase (PK) deficiency, sporadic blood transfusions are usually required when the anemia becomes severe during infectious episodes, aplastic crisis, or pregnancy.
- Therapeutic intervention with agents that can stimulate the enzyme or circumvent the defect remains experimental.
- Bone marrow transplant may cure the defect; however, the risks of bone marrow transplant outweigh the risk of the disease.
Surgical Care
For surgical care, consider splenectomy and partial splenectomy. However, reports of both failure and success exist with partial splenectomy in patients with pyruvate kinase deficiency or idiopathic thrombocytopenic purpura (ITP).
- Presurgery antibiotics: Usually prepare patients who require splenectomy by starting prophylactic antibiotics before surgery.
- Presurgery vaccines
- Polyvalent polysaccharide pneumococcal vaccine is usually administered 1-2 weeks before splenectomy (assuming such children are >2 y).
- In the rare child younger than 2 years, use the conjugated pneumococcal vaccine.
- Also administer Haemophilus influenzae type b vaccine; the conjugate form is usually administered in a series of 3 doses when the individual is aged 2, 4, and 6 months.
- Children who have already received their initial and 12-month booster doses are usually immune and do not require further vaccine before splenectomy. Quadrivalent meningococcal vaccine, used only in children older than 2 years, is also recommended. This vaccine is serogroup specific against groups A, C, Y, and W-135; it is a polysaccharide vaccine (MPSV4) with limited efficacy. The response to this vaccine is not long lasting, and it lacks the anamnestic response on subsequent challenge. For this reason, a new vaccine was licensed in 2005, which is a conjugate tetravalent vaccine (MCV4 [Menactra]). This vaccine has shown a much more durable immunity and a good anamnestic response. Unlike the polysaccharide vaccine, which should not be given to children younger than 2 years, this vaccine is effective in children in this age group. Menactra vaccine will not stimulate protection against infection caused by Neisseria meningitidis other than serogroups A, C, Y, and W-135.
- Splenectomy
- This surgical procedure is frequently performed to eliminate or to minimize the need for blood transfusion.
- Always consider splenectomy in the patient who is transfusion dependent.
- Splenectomy is not curative but may eliminate or decrease the need for blood transfusions.
- In an attempt to preserve the splenic function in a young child, 80% of the spleen was removed, with no benefit.
- A total splenectomy was performed later and proved to be effective.
- Partial splenectomy
- Partial splenectomy has been used in an attempt to keep splenic tissue to preserve some splenic function.
- Partial splenectomy is expected to protect the child from the following consequences of asplenia:
- Fulminating sepsis with the encapsulated organisms (Streptococcus pneumoniae [in >60%], H influenzae, N meningitidis)
- Streptococcal and staphylococcal infections, which affect such patients with less frequency
- Malaria and babesiosis in endemic regions
- Partial splenectomy has been attempted in various patients with different diagnoses.
- The procedure is very effective in persons with traumatic splenectomy and in individuals with some of the hemolytic anemias.
Consultations
- A hematologist should perform the initial diagnostic workup.
- Advise genetic counseling.
- Consult with a surgeon if splenectomy is considered.
Activity
- Patients with hemoglobin levels close to or slightly below the reference range tolerate normal daily activities. Those with severe anemia demonstrate exercise intolerance, and their activity is limited as a result.
- However, exercise tolerance in children with pyruvate kinase deficiency is somewhat higher than expected given their hemoglobin level. This higher tolerance is thought to be related to the fact that the block in the glycolytic pathway is distal to the production of 2,3-DPG, which accumulates in the RBC, resulting in shift of the hemoglobin-oxygen dissociation curve to the right and enabling a faster oxygen release to the tissues.
Medication
As in all persons with hemolytic anemias and because of the severe demand for folic acid, the potential for developing megaloblastic anemia in patients with pyruvate kinase (PK) deficiency can be prevented by administering 1 mg/d of folic acid. Packed RBC transfusion is reserved for persons who develop significant anemia.
Vitamins
Folic acid is used extensively in individuals with hemolytic anemias. Megaloblastic anemia may develop if folic acid is not supplied.
Folic acid (Folvite)
Important cofactor for enzymes used in production of RBCs.
Adult
5 mg/d PO
Pediatric
1 mg/d PO
Coadministration with phenytoin decreases serum phenytoin concentration, thereby increasing risk of seizures
Documented hypersensitivity
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Patients with alcoholism and deficiencies of other vitamins may develop resistance to treatment
Antibiotics
Patients who undergo splenectomy are prone to fulminating infections with encapsulated organisms, and most are sensitive to penicillins. Some clinicians recommend administration of prophylactic penicillin for 2-3 years following the procedure. Other clinicians recommend administration of prophylactic penicillin for life.
Administer erythromycin instead if the child is sensitive to penicillin.
Penicillin V potassium (Beepen-VK, Betapen-VK, Pen. VEE K)
Inhibits biosynthesis of cell wall mucopeptide.
Adult
Pediatric
<5 years: 125 mg PO bid
>5 years: 250 mg PO bid
Probenecid may increase effectiveness by decreasing clearance; tetracyclines are bacteriostatic, causing decrease in effectiveness of penicillins when administered concurrently
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
PO route is not adequate in severe infections; minimum of 10 d of therapy when treating streptococcal infections
Erythromycin (E.E.S., E-Mycin, Eryc, Ery-Tab, Erythrocin)
Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult
Pediatric
<5 years: 125 mg PO bid
>5 years: 250 mg PO bid
Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Documented hypersensitivity; hepatic impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occurs
Vaccines
Pneumococcal polyvalent vaccination (PPV-23) contains 23 serotypes that cause approximately 70% of invasive diseases caused by these organisms. Administer this vaccination 1-2 wk prior to surgery to prevent or minimize future complications. Pneumococcal 7-valent conjugate vaccine (PCV-7) contains 7 serotypes of pneumococcal bacteria largely responsible for invasive disease in young children.
Pneumococcal polyvalent vaccine, 23-valent (Pneumovax-23)
23-Polyvalent vaccine used for prophylaxis against infection from Streptococcus pneumoniae. Used in populations at increased risk of pneumococcal pneumonia (ie, >55 y, chronic infection, asplenia, immunocompromise).
Adult
0.5 mL IM/SC as a single dose
Pediatric
<2 years: Immunity may not be conferred; antibody response poor in this age group
>2 years: 0.5 mL IM/SC as single dose; repeat dose after 5 y for high-risk children (eg, functional or anatomic asplenia, conditions associated with rapid antibody decline after initial vaccination)
Note: Administer PVV-23 6-8 wk after PCV-7 (see schedule in medication table for PCV-7)
Immunosuppressive agents (large amounts of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents) may reduce effectiveness; therapy with immunoglobulin preparations is likely to block active immunity induced with pneumococcal vaccination (withhold for 3 mo after discontinuation of immunoglobulin therapy)
Documented hypersensitivity to any component or thimerosal; severe or even moderate febrile illness; thrombocytopenia or any coagulation disorder that contraindicates IM injection unless potential benefit clearly outweighs risk of administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Moderate or severe illness with or without fever; may cause arthralgia, fever, urticaria, Guillain-Barré syndrome (rare)
Pneumococcal 7-valent conjugate vaccine (Prevnar)
Sterile solution of saccharides of capsular antigens of S pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM197 protein. These 7 serotypes have been responsible for >80% of invasive pneumococcal disease in children <6 y in the United States. Also accounted for 74% of penicillin-nonsusceptible S pneumoniae (PNSP) and 100% of pneumococci with high-level penicillin resistance.
Customary age for first dose is 2 mo but can be given to infants as young as 6 wk. Preferred sites of IM injection are anterolateral aspect of the thigh in infants or deltoid muscle of upper arm in toddlers and young children. Do not inject vaccine in gluteal area or areas that may contain a major nerve trunk or blood vessel. A 3-dose series, 0.5 mL each, is initiated in infants aged 7-11 mo (4 wk apart; third dose after first birthday). Children aged 12-23 mo are given 2 doses (2 mo apart). Children >24 mo through 9 y are given 1 dose. Minor illnesses, such as a mild upper respiratory tract infection, with or without low-grade fever, are not generally considered contraindications.
Adult
Not established
Pediatric
Series initiated at age 2 months: 0.5 mL IM x 3 doses at 4-8 wk intervals, followed by a fourth dose of 0.5 mL at age 12-15 mo; administer fourth dose 2 mo or later following the third dose
Series initiated at age 7-11 months: 0.5 mL IM x 2 doses at 4 wk intervals, followed by third dose after 1-year birthday, separate second and third dose by at least 2 mo
Series initiated at age 12-23 months: 0.5 mL IM x 2 doses administered 2 mo apart
Initiated at age 2-9 years: 0.5 mL IM once
Administration of pneumococcal polysaccharide-23 (PPV-23) and pneumoccal-7 (PCV-7) vaccines should follow the schedule below for patients undergoing splenectomy at a young age.
Age 24-59 months and 4 PCV-7 doses were previously given:
PPV-23: 1 dose at 24 mo, 6-8 wk after last PCV-7; repeat 3-5 y later
Age 24-59 months and 1-3 PCV-7 doses were previously given:
PCV-7: 1 dose
PPV-23: 1 dose 6-8 wk after PCV-7; repeat 3-5 y later
Age 24-59 months and 1 PPV-23 was previously given:
PCV-7: 2 doses given 6-8 w apart
PPV-23: Repeat 3-5 y later
Age 24-59 months and no PPV-23 or PCV-7 previously given:
PCV-7: 2 doses given 6-8 w apart
PPV-23: 1 dose 6-8 wk after PCV-7; repeat 3-5 y later
Effects may decrease with immunosuppressive agents (immunosuppressive doses of corticosteroids, antimetabolites, alkylating agents, cytotoxic agents); pneumococcal 7-valent conjugate vaccine may increase effects of anticoagulant therapy; globulin preparations may interfere with immune response to PPV-23 and reduce efficacy (do not administer within 6-8 wk of vaccine)
Documented hypersensitivity to any component or diphtheria toxoid; severe or moderate febrile illness; infants or children with thrombocytopenia or coagulation disorder that contraindicates IM injection (unless benefits outweigh risks of administration)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
For IM use only (do not administer IV under any circumstances); take special care to prevent injection into or near a blood vessel or nerve; caution in patients with possible history of latex sensitivity (packaging contains dry natural rubber); use of pneumococcal conjugate vaccine does not replace use of PPV-23 in children >24 mo with sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immunocompromised; caution in patients with coagulation disorders
Haemophilus b conjugate vaccine (ActHIB, HibTITER, PedvaxHIB)
Used for routine immunization of children against invasive diseases caused by H influenzae type b. Decreases nasopharyngeal colonization. The CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children receive one of the conjugate vaccines licensed for infant use beginning routinely at age 2 mo. Conjugate forms are usually given in series of 3 doses at ages 2, 4, and 6 mo. Children who have received primary vaccinations and booster dose at age 12 mo or older are usually protected and do not need further vaccinations prior to splenectomy.
Adult
Not indicated
Pediatric
Regimens vary depending on product; the use of HibTITER is the example that follows:
2-6 months: 0.5 mL IM q2mo for 3 doses
7-11 months: 0.5 mL IM q2mo for 2 doses if previously unvaccinated
12-14 months: 0.5 mL IM once if previously unvaccinated
Booster dose: All children receive 0.5 mL at age 15 mo or at least 2 mo after last dose of immunization series; for children aged 15-71 mo and previously unvaccinated, 0.5 mL IM is given only once
Immunoglobulins given within 1 mo or concurrent administration with immunosuppressive agents may inhibit full immunologic response
Documented hypersensitivity; immunosuppressed children or those receiving immunosuppressive therapy; IV/ID/SC administration
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Delay immunization upon evidence of febrile illness; may cause local erythema, swelling, or tenderness; risk of Haemophilus type b infections increases the week after vaccination; cause-effect relationship with observed postvaccine Guillain-Barré syndrome has not been established; serious adverse reactions should be reported to
US Department of Health and Human Services (800-822-7967)
More on Pyruvate Kinase Deficiency |
| Overview: Pyruvate Kinase Deficiency |
| Differential Diagnoses & Workup: Pyruvate Kinase Deficiency |
 Treatment & Medication: Pyruvate Kinase Deficiency |
| Follow-up: Pyruvate Kinase Deficiency |
| Multimedia: Pyruvate Kinase Deficiency |
| References |
| « Previous Page | Next Page » |
References
Dacie JV, Mollison PL, Richardson N, et al. Atypical congenital haemolytic anaemia. Q J Med. Jan 1953;22(85):79-98. [Medline].
Diez A, Gilsanz F, Martinez J, et al. Life-threatening nonspherocytic hemolytic anemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression. Blood. Sep 1 2005;106(5):1851-6. [Medline].
Ayi K, Min-Oo G, Serghides L, Crockett M, Kirby-Allen M, Quirt I. Pyruvate kinase deficiency and malaria. N Engl J Med. Apr 24 2008;358(17):1805-10. [Medline].
Kedar PS, Warang P, Colah RB, Mohanty D. Red cell pyruvate kinase deficiency in neonatal jaundice cases in India. Indian J Pediatr. Nov 2006;73(11):985-8. [Medline].
Raphael MF, Van Wijk R, Schweizer JJ, et al. Pyruvate kinase deficiency associated with severe liver dysfunction in the newborn. Am J Hematol. Nov 2007;82(11):1025-8. [Medline].
Hilgard P, Gerkin G. Liver cirrhosis as a consequence of iron overload caused by hereditary non-spherocytic hemolytic anemia. World J Gastroenterol. Feb 2005;11(8):1241-4. [Medline].
Finkenstedt A, Bianchi P, Theurl I, et al. Regulation of iron metabolism through GDF15 and hepcidin in pyruvate kinase deficiency. Br J Haematol. Mar 2009;144(5):789-93. [Medline].
Rao A, Hulbert M, Wilson DB. Severe hypertriglyceridemia in an infant with red cell pyruvate kinase deficiency. Indian Pediatr. Apr 2007;44(4):303-5. [Medline].
[Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94. [Medline]. [Full Text].
Aizawa S, Kohdera U, Hiramoto M, et al. Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency. Am J Hematol. Sep 2003;74(1):68-72. [Medline].
Nathan DG, Oski FA. Hematology of Infancy and Childhood. 5th ed. Philadelphia, Pa: WB Saunders Co; 1998.
Nathan DG, Oski FA, Sidel VW, Diamond LK. Extreme hemolysis and red-cell distortion in erythrocyte pyruvate kinase deficiency. II. Measurements of erythrocyte glucose consumption, potassium flux and adenosine triphosphate stability. N Engl J Med. Jan 21 1965;272:118-23. [Medline].
Rennels M, King J, Ryall R, et al. Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants. Pediatr Infect Dis J. May 2004;23(5):429-35. [Medline].
Robinson MA, Loder PB, de Gruchy GC. Red-cell metabolism in non-spherocytic congenital haemolytic anaemia. Br J Haematol. Jul 1961;7:327-39. [Medline].
Sandoval C, Stringel G, Weisberger J. Failure of partial splenectomy to ameliorate the anemia of pyruvate kinase deficiency. J Pediatr Surg. Apr 1997;32(4):641-2. [Medline].
Tanaka KR, Valentine W, Miwa S. Pyruvate kinase (PK) deficiency hereditary nonspherocytic hemolytic anemia. Blood. Mar 1962;19:267-95. [Medline].
Valentine WE, Tanaka KR, Miwa S. A specific erythrocyte glycolytic enzyme defect (pyruvate kinase) in three subjects with congenital non-spherocytic hemolytic anemia. Trans Assoc Am Physicians. 1961;74:100-10. [Medline].
Zanella A, Fermo E, Bianchi P, Valentini G. Red cell pyruvate kinase deficiency: molecular and clinical aspects. Br J Haematol. Jul 2005;130(1):11-25. [Medline]. [Full Text].
Zanella A, Fermo E, Bianchi P,etal. Pyruvate Kinase deficiency : The genotype-phenotype association. Blood Rev. Jul; 2007;(4):217-31. [Medline].
Zarza R, Pujades A, Garcia J, et al. [Molecular study of red cell pyruvate kinase deficiency in 15 patients with chronic hemolytic anemia. Group of Erythropathology of Hematology and hemotherapy Association of Spain (HHAS)]. Med Clin (Barc). May 8 1999;112(16):606-9. [Medline].
Zuelzer WW, Robinson AR, Hsu TH. Erythrocyte pyruvate kinase deficiency in non-spherocytic hemolytic anemia: a system of multiple genetic markers?. Blood. Jul 1968;32(1):33-48. [Medline].
Further Reading
Keywords
pyruvate kinase deficiency, PK deficiency, PKD, congenital nonspherocytic hemolytic anemia type II, CNSHA type II, hereditary spherocytosis, HS, adenosine triphosphate, ATP, hemolysis, 2, 3-diphosophoglycerate, 2, 3-DPG, PK-deficient reticulocytes, bilirubin level, anemia, idiopathic thrombocytopenic purpura, ITP, immune hemolysis, anaerobic glycolytic pathway, lactate, hemoglobin-oxygen dissociation curve, splenectomy, hyperbilirubinemia, nonimmune hydrops fetalis, jaundice, splenomegaly, gallbladder stones, exercise tolerance, fulminating infections
