Approach Considerations
In patients with mild to moderate pyruvate kinase deficiency, care is predominantly supportive. High-impact contact sports are contraindicated in patients with significant splenomegaly. Red blood cell transfusion may be necessary if the hemoglobin value falls significantly; this tends to occur in early childhood and during periods when physiologic stress is present, such as when an infection exists or during pregnancy.
In pregnant patients with pyruvate kinase deficiency, uncomplicated pregnancy, delivery, and birth have been reported despite a decline in the hemoglobin value to 6.8 g/dL during pregnancy. [32] In one study of pregnant patients, significant puerperal jaundice was successfully treated with conservative measures. [33]
Supplemental folic acid and other B vitamins help to prevent deficiencies from increased erythrocyte production.
Large doses of salicylates should be avoided in patients with severe anemia, because these inhibit oxidative phosphorylation, thereby causing further ATP depletion.
Therapeutic intervention with agents that can stimulate pyruvate kinase or circumvent the deficiency defect remains experimental. [34]
An international, multicenter registry that collected clinical data on patients with pyruvate kinase deficiency found that 93% of newborns were treated with phototherapy, and 46% were treated with exchange transfusions. Splenectomy was performed in 150 of 254 patients, or 59%, and was associated with a median increase in hemoglobin levels of 1.6 g/dL along with a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included higher presplenectomy hemoglobin, lower indirect bilirubin, and missense PKLR mutations. In total, 87 of 254 patients, or 34%, had both a splenectomy and cholecystectomy. In patients who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. [6]
Activity
Patients with hemoglobin levels close to or slightly below the reference range can tolerate normal daily activities. Those with severe anemia demonstrate exercise intolerance, and their activity is limited as a result.
Transfusion
Transfusions can be used as follows in the management of pyruvate kinase deficiency:
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Intrauterine transfusion: Required in most patients with extremely severe fetal anemia associated with hydrops fetalis
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Phototherapy or exchange transfusion: Required for most newborns with severe hyperbilirubinemia
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Simple blood transfusion: Administered for anemia during early childhood and, occasionally, into adulthood.
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Sporadic blood transfusions: Required in most older patients when anemia becomes severe during infectious episodes, aplastic crisis, or pregnancy
Bone Marrow Transplantation
Although a bone marrow transplant may cure the defect in pyruvate kinase deficiency, the risks of the procedure outweigh those of the disease. Nonetheless, it was reported that a boy aged 5 years with severe hemolytic anemia due to pyruvate kinase deficiency and heterozygous hemoglobin E underwent bone marrow transplantation using ABO-identical and human leukocyte antigen (HLA) ̶ identical marrow from his sister. More than 3 years posttransplant, the patient was still healthy, without symptomatology. [35]
Splenectomy
For surgical care, consider splenectomy or partial splenectomy, although both failure and success have been reported in patients with pyruvate kinase deficiency or idiopathic thrombocytopenic purpura who underwent partial splenectomy.
Presurgery antibiotics
Patients who require splenectomy should usually be prepared by starting prophylactic antibiotics before surgery.
Presurgery vaccines
Vaccines used prior to splenectomy include the following:
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Polyvalent polysaccharide pneumococcal vaccine: Administered 1-2 weeks before splenectomy in patients over age 2 years
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Haemophilus influenzae type b vaccine: The conjugate form is usually administered to children at age 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 vaccination before splenectomy
Quadrivalent meningococcal vaccine (MPSV4), a polysaccharide vaccine used only in patients over age 2 years, is also recommended. It is serogroup specific for groups A, C, Y, and W-135. Its efficacy, however, is limited; response to the vaccine is not long lasting, and it lacks an anamnestic response on subsequent challenge.
For this reason, the conjugate tetravalent vaccine MCV4 (Menactra) was licensed in 2005. It has a much more durable immunity, as well as a good anamnestic response, and unlike the polysaccharide vaccine, it can be administered to children younger than 2 years.
Procedure
Splenectomy is indicated only for patients with severe anemia or symptomatic hypersplenism. The procedure does not abolish hemolysis or improve mild anemia, but it can reduce severe anemia and is frequently performed to minimize or eliminate the patient's need for blood transfusion.
Splenectomy should be performed by an experienced surgeon, especially in pediatric patients. Consider the susceptibility to infection following splenectomy, especially in children younger than 5 years. Prophylactic antibiotics should be administered to young patients postsplenectomy. [38] Always monitor patients with splenectomies for possible fulminating infection.
After the surgery, the patient’s hemoglobin concentration typically increases by 1-3 g/dL. Transfusion requirements typically decrease, the danger of an aplastic crisis with infection is reduced, and growth delay, if present, may be reversed and catch-up growth ensue.
Partial splenectomy
Partial splenectomy is used to preserve some splenic function in the patient and to protect against the following consequences of asplenia:
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Fulminating sepsis with encapsulated organisms: Streptococcus pneumoniae (in >60%), H influenzae, and Neisseria meningitidis
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Streptococcal and staphylococcal infections (which affect such patients with less frequency)
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Malaria and babesiosis (in endemic regions)
The procedure is very effective in persons with traumatic splenectomy and in individuals with some of the hemolytic anemias.
Consultations
When necessary, the following specialists should be consulted:
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Hematologist: For management and treatment
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Surgeon: If splenectomy is considered
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Anesthesiologist: For presurgical management if anemia is severe
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Gastroenterologist: To help evaluate complications of the biliary tree
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Peripheral blood smear in a child with splenectomy and pyruvate kinase deficiency.
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The Embden-Meyerhof pathway.
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Pyruvate kinase in the Embden-Meyerhof pathway.
