Approach
The management of HS generally depends on the severity of the hemolysis and degree of anemia, but for most patients it is supportive.[5]
Blood transfusions may be indicated during infancy and during periods of increased hemolysis or aplastic crisis. No defined hemoglobin cut-off exists to determine when a blood transfusion is indicated, but the decision must be based on the decline of hemoglobin from baseline values, and on the symptoms of anemia.
Patients should be referred to a hematology specialist once the diagnosis of HS is suspected for definitive diagnosis, routine monitoring, and management.
Severity criteria
HS can be clinically classified based on the severity of the anemia and symptoms, and managed accordingly.[1]
Trait
Hemoglobin: normal
Reticulocytes <3%
Bilirubin <1 mg/dL (<17 micromol/L)
Splenectomy not required
Mild
Hemoglobin 11 to 15 g/dL
Reticulocytes 3% to 6%
Bilirubin 1 to 2 mg/dL (17-34 micromol/L)
Splenectomy usually not necessary
Moderate
Hemoglobin 8 to 12 g/dL
Reticulocytes >6%
Bilirubin >2 mg/dL (>34 micromol/L)
Splenectomy may be necessary before puberty
Severe
Hemoglobin <6 to 8 g/dL
Reticulocytes >10%
Bilirubin >3 mg/dL (>51 micromol/L)
Splenectomy necessary, delay until >6 years of age if possible
The assessment of HS severity should be made when the patient is well. Symptoms and signs may fluctuate during the course of the condition. For instance, following acute infection with parvovirus B19, patients may develop aplastic crisis.[17] The virus directly attacks erythroid precursors in the bone marrow and results in erythroid aplasia for about 10 days. The hemoglobin value is usually between 3 and 6 g/dL. Reticulocyte count is typically <1%. During the recovery phase the reticulocyte count increases, and following recovery from an aplastic crisis, permanent immunity usually results. This infection may unmask hitherto undiagnosed HS in a family.
Far more common, but less severe than aplastic episodes, are hyperhemolytic crises, which cause an episode of acceleration of the usual hemolytic process. Episodes usually accompany nonspecific viral infections, in which the reticuloendothelial system undergoes hyperplasia, with further enlargement of the spleen. In contrast to an aplastic crisis, the hemoglobin (Hb) is usually in the 5 to 8 g/dL range (or even higher during milder episodes), the reticulocyte count is elevated, and the patient is more jaundiced than usual. The spleen rarely may become acutely and significantly enlarged and cause left upper quadrant abdominal pain and symptoms of early satiety. The spleen generally shrinks to its previous size between episodes.
Neonatal period (<28 days old)
When HS is diagnosed in the neonatal period it is likely to be more severe, with up to 76% of affected newborns requiring one or more transfusions during the first 6 to 12 months of life, despite often having normal Hb values immediately following birth.[28]
Newborns are often not capable of maintaining an adequate Hb during the first several months of life. This is due to ongoing hemolysis and an inability to mount an adequate reticulocyte response during their physiologic Hb nadir (which occurs at 8-12 weeks of life). Red-cell transfusions may be necessary during this period to maintain a Hb of 7 to 8 g/dL. This may be required until the reticulocyte count improves and the child is able to maintain adequate Hb concentration without transfusion. The transfusion requirement early in life does not appear to predict the severity of the disease or the need for continued regular transfusions beyond the first year of life.[28] Folic acid supplementation may also be given.
Neonatal jaundice occurs in about 50% of patients with HS. Jaundice typically occurs within the first 24 hours of life and bilirubin levels may reach levels at which treatment with phototherapy and/or exchange transfusion is indicated. Current guidelines for neonatal jaundice should be followed to determine appropriateness of therapy.[29] See Neonatal jaundice.
Infants (>28 days old), children, and adults: severe HS
Splenectomy is generally considered the treatment of choice in patients with severe HS.[5][30][31]
Patients should be managed with transfusions for symptomatic anemia until a time when splenectomy is deemed appropriate. Beyond the neonatal period most patients can tolerate a Hb value as low as 6 g/dL without the need for regular transfusions. Supportive care with red-cell transfusions may be required, particularly if infection with parvovirus B19 results in aplastic crisis or during episodes of hyperhemolytic crises.
It is best to avoid surgical splenectomy until at least 6 years of age to reduce the risk of postsplenectomy sepsis. However, patients with the most severe anemia requiring regular transfusions may be candidates for splenectomy at a younger age (generally not prior to 2 years of age).
In addition to other therapy, patients with significant hemolysis (e.g., with a reticulocyte count of >5%) may benefit from folic acid supplementation to prevent megaloblastic anemia. There are no studies to establish best practice.
Reducing risk of sepsis
Postsplenectomy sepsis remains a significant risk despite appropriate precautions.[30] Overwhelming sepsis due to Streptococcus pneumoniae was recognized many decades ago and was noted to be highest in young children in the early years after splenectomy.[32][33][34][35] The risk of sepsis persists lifelong. Presplenectomy vaccination and postsplenectomy antibiotics reduce the risk, but they do not eliminate it.[31][36] CDC: ACIP vaccine recommendations and guidelines Opens in new window
Vaccination
Patients undergoing splenectomy should be immunized with vaccines against S pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis.[36][37][38] CDC: ACIP vaccine recommendations and guidelines Opens in new window
Three vaccines against pneumococcal disease are recommended: two pneumococcal conjugate vaccines (PCV15 and PCV20) and a pneumococcal polysaccharide vaccine (PPSV23). Choice of pneumococcal vaccine depends upon the age of the patient (minimum age: 6 weeks [PCV15], [PCV 20]; 2 years [PPSV23]) and medical status.[38][39][40]
Consult local schedules for pneumococcal vaccination recommendations (and catch up guidance) in patients undergoing splenectomy.[39][40][41] UK HSA: UK immunisation schedule: the green book, chapter 11 Opens in new window
Children with anatomic or functional asplenia should be vaccinated with the quadrivalent meningococcal conjugate vaccine; those ages ≥10 years should receive the meningococcal serogroup B vaccine.
For elective splenectomy, immunizations should be given at least 2 weeks in advance of surgery if feasible.[37] However, they are also effective when given after splenectomy.
Vaccines should be administered according to recommended vaccination schedules and preoperatively as required. CDC: Immunization schedules Opens in new window UK HSA: UK immunisation schedule: the green book, chapter 11 Opens in new window
Surgical procedure
Splenectomy is best performed laparoscopically as it is associated with less pain and a quicker recovery than laparotomy, but this will depend upon local expertise and equipment. An alternative to full splenectomy is to remove part of the spleen with the intention of leaving enough behind to preserve immune function.[42] This has some limitations, and in the absence of convincing comparative studies remains an investigative procedure.[43]
Management of gallstones
Gallstones are common in HS and may be present in the first decade, increasing with age to up to 50% by 50 years of age.[44] Some authors recommend regular screening for detection of gallstones, but there are no studies to support this.[44]
Ultrasound of the gallbladder should be performed prior to splenectomy. If there are symptomatic stones at the time of splenectomy, the gallbladder is removed simultaneously. If asymptomatic gallstones are detected, options are as follows:
Splenectomy alone
Removal of stones leaving the gallbladder (cholecystotomy) with splenectomy, on the basis that the risk of stone formation is removed with the splenectomy
Cholecystectomy (in addition to splenectomy)
Gallstones will not form following successful splenectomy.
Postsplenectomy
Twice-a-day prophylactic penicillin should be administered for at least 3 years following splenectomy, and some practitioners advocate lifelong penicillin prophylaxis.[36] Guidelines vary from one country to another and there is no clear evidence to guide practice.[16]
The postsplenectomy risk of overwhelming infection varies, and those at highest risk should be offered lifelong antibiotic prophylaxis. For example, those over 50 years of age, those with a documented inadequate response to vaccination, a history of previous invasive pneumococcal disease, or underlying hematologic malignancy, particularly if immunosuppression is ongoing. Patients should carry a supply of appropriate antibiotics for emergency use. If penicillin is not used (for example, in areas with documented resistant strains), an alternative antibiotic to protect against pneumococcal infection may be appropriate. Amoxicillin has been recommended, and people who are allergic to penicillin may use erythromycin instead.[36] Folic acid is not required postsplenectomy.
Infants (>28 days old), children, and adults: mild-to-moderate HS
The management of mild-to-moderate HS is generally supportive, at least during early childhood.
Red-cell transfusions may be required, particularly if infection with parvovirus B19 results in aplastic crisis or during episodes of hyperhemolytic crises. Patients likely to benefit from splenectomy include those with moderate, symptomatic anemia; those who have had recurrent hyperhemolytic crises; and those requiring multiple transfusions.
In patients with milder disease, the risks and benefits of splenectomy must be carefully weighed on an individual basis.[30] Splenectomy may be warranted in mild HS for issues related to reduced quality of life, such as bothersome jaundice, fatigue, poor growth, or poor school performance.
Presplenectomy vaccination schedules are the same as those described for patients with severe HS. The management of gallstones in patients due to undergo splenectomy is the same as that described for those with severe disease. There is some evidence that it is not always necessary to remove the spleen at the same time as performing surgery for symptomatic gallstones; each case should be assessed on its own merits.[45]
Folic acid supplementation is indicated as described for severe HS before splenectomy.[5] It is likely not to be necessary in mild disease as many foods are now supplemented with folic acid, and deficiency is very rare in developed countries. Folic acid is not required postsplenectomy.
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