Hereditary Spherocytosis Treatment & Management

Neonates with severe hyperbilirubinemia caused by hereditary spherocytosis (HS) are at risk for kernicterus. These infants should be treated with phototherapy and/or exchange transfusion as clinically indicated.

Aplastic crises occasionally can cause the hemoglobin level to fall because of ongoing destruction of spherocytes that is not balanced by new red blood cell (RBC) production. RBC transfusions often are necessary in these cases.

Folic acid is required to sustain erythropoiesis. Patients with HS are instructed to take supplementary folic acid for life in order to prevent a megaloblastic crisis. During the first 6 years of life, if patients have compensated anemia, are growing well, and can keep up with their peers in most activities, limiting folic acid supplementation to 1 mg/d is prudent.

Splenectomy is the definitive treatment for HS. ^[6] Except in the unusual autosomal recessive variant of HS, splenectomy usually eliminates hemolysis and the associated signs and symptoms. ^[7] Interestinagly, splenectomy does little to correct the cytoskeletal membrane defects of HS; an atomic force microscopy study by Li et al found that after splenectomy, erythrocytes were larger but still spheroidal-shaped, with a disorganized membrane ultrastructure and reduced surface particle size. ^[25]

Splenectomy may fail to control HS because of any of the following:

• An accessory spleen
• Accidental autotransplantation of splenic tissue into the peritoneum during surgery
• Another hemolytic disorder
• Splenosis

Indications for splenectomy are not always clear. ^[26] Little doubt exists that patients with more severe anemia (hemoglobin level < 8 g/dL) and symptoms and complications of HS should undergo splenectomy. By the same token, splenectomy can be deferred safely in patients with mild uncomplicated HS (hemoglobin level > 11 g/dL). No good studies have been performed that provide a basis for clinical judgments in patients with moderate asymptomatic HS (hemoglobin level 8-11 g/dL).

Children who are candidates for splenectomy include those with severe HS requiring RBC transfusions and those with moderate HS who manifest growth failure or other signs and symptoms of anemia. Splenectomy for children with HS should not be performed until the child is older than 6 years, to reduce the risk of infections with encapsulated bacteria.

An interesting alternative approach in pediatric patients has been the use of partial splenectomy to retain splenic immunologic function while at the same time reducing the rate of hemolysis. ^[27] This appears to both control hemolysis and preserve splenic function.

RBC survival improves significantly after splenectomy but does not become absolutely normal. The mean corpuscular volume (MCV) usually falls, but the mean corpuscular hemoglobin concentration (MCHC) does not change significantly.

In children with HS who underwent total or partial splenectomy, a review found that the hemoglobin concentration increased from 10.1 ± 1.8 g/dL at baseline to 12.8 ± 1.6 g/dL at 52 weeks postoperatively. In addition, splenectomry resulted in a decrease in reticulocyte counts and bilirubin levels as well as control of symptoms. ^[28]

Other postsplenectomy blood changes include the following:

• Increased hemoglobin level
• Decreased reticulocyte count
• Leukocytosis
• Thrombocytosis

On the peripheral blood smear, spherocytes continue to appear. Expected changes on peripheral blood smears include the appearance of Howell-Jolly inclusion bodies and target cells. Absence of Howell-Jolly bodies on the peripheral blood smear in splenectomized patients may indicate the presence of functional splenic activity.

Fatal sepsis caused by capsulated organisms (eg, Streptococcus pneumoniae, Haemophilus influenzae) is a recognized complication in children who have had a splenectomy. The estimated rate of mortality from sepsis in these children is approximately 200 times greater than that expected in the general population. Although most septic episodes have been observed in children whose spleens were removed in the first years of life, older children and adults also are susceptible.

Vaccination against pneumococcus and H influenzae must be administered to patients prior to splenectomy and, indeed, probably to all patients with severe HS. If a partial splenectomy is performed, splenic function is preserved and vaccinations may be delayed until after surgery; however, the long-term data are not well established.

Bilirubin gallstones are found in approximately 50% of patients with HS and frequently are present in patients with very mild disease. Therefore, periodic ultrasonic evaluation of the gallbladder should be performed.

If surveillance ultrasound examinations reveal gallstones, performing a prophylactic laparoscopic cholecystectomy seems reasonable. This procedure helps prevent significant biliary tract disease and, in some patients with mild HS, helps avoid the need for splenectomy. In patients with bilirubin stones who are candidates for splenectomy, a simultaneous cholecystectomy may eliminate future complications and the need for a second operative procedure.

Generally, the treatment of HS involves presplenectomy care, splenectomy, and management of postsplenectomy complications. In pediatric cases, splenectomy ideally should not be performed until a child is older than 6 years because of the increased incidence of postsplenectomy infections with encapsulated organisms such as S pneumoniae and H influenzae in young children. Partial splenectomies are increasingly used in pediatric patients, as this approach appears to both control hemolysis and preserve splenic function.

European guidelines on splenectomy for HS note that a laparoscopic approach is currently considered the gold standard for removal of a normal-sized or slightly enlarged spleen and is preferred to open splenectomy, but it should be performed only by experienced surgeons. In children undergoing splenectomy, the gallbladder should be removed concomitantly if the patient has symptomatic gallstones . The study group could not come to consensus on the use of partial splenectomy. ^[29]

In a study of 79 patients who underwent subtotal splenectomy (85-95% removal), with mean follow-up of approximately 11 years (range, 3-23 years), Pincez et al reported that the benefits varied according to disease severity. In children younger than 6 years with severe disease, the procedure reduces the transfusion rate and increases the hemoglobin to a level compatible with normal growth and activity. Half of those patients will not require total splenectomy; the other half will require it at an age when it will be much safer. ^[30]

In a study that included 12 patients who underwent subtotal splenectomy at a mean age of 6.5 years, Rosman et al reported that in three children, the procedure was unsuccessful because no functional splenic remnant remained after 6 months; four children required secondary splenectomy for hematologic recurrence after a median of 5 years; and in the remaining five patients, a functional splenic remnant was present for at least 5.5 years. ^[31]

In patients with intermediate HS, subtotal splenectomy avoids the long-term risk of infections and vascular events associated with total splenectomy. However, it comes with the cost of persistence of a lower but persistent hemolytic state. ^[30]

A retrospective review by Abdullah et al of splenectomy for HS in over 1650 children found that the morbidity and mortality are low, and that performance of concurrent cholecystectomy and/or appendectomy is safe. In addition, Abdullah et al found that of 13 potentially avoidable complications identified as pediatric quality indicators by the Agency for Healthcare Research and Quality (AHRQ), none occurred in more than 1% of the splenectomized children. ^[7]

If the diagnosis of HS is unclear after routine testing or the patient has severe episodes of hemolysis, consultation with a hematologist is warranted because the patient may have a variant of HS or more than one hemolytic disease. A hematologist also may provide treatment advice regarding iron overload for patients who have an extensive transfusion history or for those who have been receiving prolonged oral iron supplementation.

Patients with HS who have recurring episodes of severe hemolysis should be evaluated by a surgeon for possible splenectomy, because splenectomy provides the greatest chance for control of their disease. A partial splenectomy can be considered if a surgeon experienced in this procedure is available. Another reason for consulting a surgeon is for the complications of gallstone formation and for the prevention of gallstones in those patients with continued hemolysis.

Lifelong folic acid supplementation is recommended for patients with HS because of their chronic hemolysis. This is especially true for those who have not undergone splenectomy. After splenectomy, all patients should have immunizations updated as needed, especially those covering encapsulated organisms. Vaccination against S pneumonia and H influenzae is of particular importance.