Approach
The management of hereditary spherocytosis (HS) generally depends on the severity of the haemolysis and degree of anaemia, but for most patients it is supportive.[7]
Blood transfusions may be indicated during infancy and during periods of increased haemolysis or aplastic crisis.[7][23][43] No defined haemoglobin (Hb) cut-off exists to determine when a blood transfusion is indicated, but the decision must be based on the decline of Hb from baseline values, and on the symptoms of anaemia.
Patients should be referred to a haematology 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 anaemia and symptoms and managed accordingly.[3][4]
Trait
Haemoglobin: normal
Reticulocytes: <3%
Bilirubin: <17 micromol/L (<1 mg/dL)
Splenectomy: not required
Mild
Haemoglobin: 110 to 150 g/L (11-15 g/dL)
Reticulocytes: 3% to 6%
Bilirubin: 17 to 34 micromol/L (1-2 mg/dL)
Splenectomy: usually not necessary
Moderate
Haemoglobin: 80 to 120 g/dL (8-12 g/dL)
Reticulocytes: >6%
Bilirubin: >34 micromol/L (>2 mg/dL)
Splenectomy: may be necessary before puberty
Severe
Haemoglobin: <60 to 80 g/dL (<6-8 g/dL)
Reticulocytes: >10%
Bilirubin: >51 micromol/L (>3 mg/dL)
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.[20][21]
Far more common, but less severe than aplastic episodes, are hyperhaemolytic crises, which cause an episode of acceleration of the usual haemolytic process. Episodes usually accompany non-specific viral infections, and may be repetitive.
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.[43]
Newborns are often not capable of maintaining an adequate Hb during the first several months of life. This is due to ongoing haemolysis and an inability to mount an adequate reticulocyte response during their physiological Hb nadir (which occurs at 8-12 weeks of life). Red-cell transfusions may be necessary during this period to maintain Hb of 70 to 80 g/L (7-8 g/dL). Transfusions 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.[43] Folic acid supplementation may be given.
Neonatal jaundice is common in HS.[7][23] 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.[44] 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.[7][45][46]
Patients should be managed with transfusions for symptomatic anaemia until splenectomy is deemed appropriate.
Beyond the neonatal period, most patients can tolerate a Hb value as low as 60 g/L (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 hyperhaemolytic crises.
It is best to avoid surgical splenectomy in children aged ≤6 years to reduce the risk of post-splenectomy sepsis.[7][46] However, patients with the most severe anaemia requiring regular transfusions may be candidates for splenectomy at a younger age (generally not prior to 2 years of age).
Patients with significant haemolysis (e.g., with a reticulocyte count of >5%) may benefit from folic acid supplementation to prevent megaloblastic anaemia. There are no studies to establish best practice.
Reducing risk of sepsis
Post-splenectomy sepsis remains a significant risk (particularly attributable to pneumococcal species), despite appropriate precautions.[7][45][46] The risk of sepsis persists lifelong. Pre-splenectomy vaccination and post-splenectomy antibiotics reduce the risk, but they do not eliminate it.[46][47] CDC: ACIP vaccine recommendations and guidelines Opens in new window
Vaccination
Patients undergoing splenectomy should be immunised with vaccines against S pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis.[47][48][49] CDC: ACIP vaccine recommendations and guidelines Opens in new window
Two vaccines against pneumococcal disease are recommended: a pneumococcal conjugate vaccine (PCV15, PCV20, or PCV21), or a pneumococcal polysaccharide vaccine (PPSV23). Choice of pneumococcal vaccine depends upon the age of the patient and medical status.[49][50][51]
Asplenic (anatomical or functional) children should be vaccinated with the quadrivalent meningococcal conjugate vaccine (MenACWY-CRM or MenACWY-TT); those aged ≥10 years should receive the meningococcal serogroup B vaccine (MenB-4C or MenB-FHbp).[50] Children aged 10 years or older may receive a dose of the pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp) as an alternative to separate administration of the quadrivalent meningococcal vaccine and the meningococcal serogroup B vaccine when both vaccines would be given on the same clinic day.[50]
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.[7][46]
An alternative to full splenectomy is to remove part of the spleen (partial splenectomy) with the intention of leaving enough splenic tissue behind to preserve immune function.[52] Partial splenectomy may, theoretically, reduce the risk for post-splenectomy sepsis, but completion splenectomy may be required to address recurrence of haematological problems or clinically significant abdominal pain.[46][53][54][55]
Meta-analysis of observational studies suggests that total splenectomy increases Hb levels and reduces reticulocytes to a greater extent than partial splenectomy at 1 year.[53] One subsequently published study reported no difference between total and partial splenectomy Hb levels 5 years post procedure.[56] Formal clinical trials with long-term follow-up are required.[45][46][57]
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.[14] Some authors recommend regular screening for detection of gallstones, but there are no studies to support this.[14]
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.[7][46] If asymptomatic gallstones are detected, options are as follows:[7]
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. Follow-up with ultrasound.
Cholecystectomy (in addition to splenectomy)
Gallstones will not form following successful splenectomy.[7]
Post-splenectomy
Prophylactic penicillin should be administered for at least 3 years following splenectomy; some practitioners advocate lifelong penicillin prophylaxis.[47] Guidelines vary from one country to another and there is no clear evidence to guide practice.[24]
Lifelong antibiotic prophylaxis should be offered to the following patients who are at high risk for overwhelming infection post-splenectomy:
over 50 years of age;
with a documented inadequate response to vaccination;
with a history of previous invasive pneumococcal disease;
with an underlying haematological malignancy, particularly if immunosuppression is ongoing.
Patients should carry a supply of appropriate antibiotics for emergency use. If penicillin is not used (e.g., in areas with documented resistant strains), an alternative antibiotic to protect against pneumococcal infection may be appropriate. Amoxicillin has been recommended; people who are allergic to penicillin may use erythromycin.[47] Folic acid is not required post-splenectomy.
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 hyperhaemolytic crises. Patients likely to benefit from splenectomy include those with moderate, symptomatic anaemia; those who have had recurrent hyperhaemolytic 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.[45] 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.
Pre-splenectomy 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.[58]
Folic acid supplementation is indicated as described for severe HS before splenectomy.[7] It is likely not to be necessary in mild disease as many foods are supplemented with folic acid, and deficiency is rare in developed countries. Folic acid is not required post-splenectomy.
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