What is hereditary spherocytosis?
Hereditary spherocytosis (HS) is one of the most common, inherited hemolytic anemias. It is caused by a defect in the protein that forms the outer membrane of the red blood cell. The defect causes the red blood cell to have a spherical or round shape. The change in shape makes these red blood cells break down more quickly than normal red blood cells. Most of these red blood cells are destroyed within the spleen.
Hereditary spherocytosis occurs in all racial and ethnic groups but is more common in northern Europeans, where it affects at least one person in 5,000. This form of anemia is inherited, which means it is can be passed on from one generation to another within a family.
What are the signs and symptoms of HS?
Patients with HS may have various signs and symptoms related to anemia. In additions they may have the following symptoms specific to HS:
- Abdominal pain. Patients with HS may have abdominal pain because of an enlarged spleen. As the spleen enlarges, the capsule of the spleen stretches. This also may cause the patient to have pain on the left side of the abdomen. Patients with HS also may have pain if they have gallstones. This pain may be intermittent and is generally in the right upper abdomen.
- Enlarged spleen. Many of the patients with HS have enlarged spleens, which can be felt when a doctor is doing a physical examination and/or may be seen as distension in the abdomen.
- Jaundice. Some patients with HS are jaundiced or have a yellow hue to their skin. This is because they have an elevated serum bilirubin. Bilirubin is produced when red blood cells are destroyed within the body. This jaundice may become more pronounced when a patient with HS is having a hemolytic crisis. (See more information below in the section about complications.)
How is HS diagnosed?
Patients with HS may be diagnosed at any age. If there is a family history of HS, or if a child is more severely affected, the diagnosis often is made in early infancy. If there is no family history and the disease is mild, the diagnosis of HS may be delayed into childhood, adolescence or even adult life.
To help determine the diagnosis, the following tests may be performed on your child's blood:
- Hemoglobin. Patients with HS often are anemic although the severity of anemia may vary greatly. No matter what a patient's baseline hemoglobin, that hemoglobin level may fall quickly during a hemolytic crisis. (See more information below in the section about complications.)
- Reticulocyte count. The reticulocyte count is a measure of the new red blood cells that are being produced in the bone marrow. This number is increased in HS because these patients are trying to compensate for the destruction of red blood cells. During an aplastic crisis (see more information below in the section about complications.) this number may fall as the bone marrow fails to keep up with the destruction of red blood cells.
- Osmotic fragility. This is the test performed to make the diagnosis of HS. The patient's red blood cells are suspended in a salt solution and their destruction or fragility is measured. If this test is abnormal, a genetic test for the specific mutation associated with HS can be performed.
- Bilirubin. Bilirubin is produced when red blood cells are destroyed within the body. Red blood cells are destroyed more quickly in HS and this causes the serum bilirubin to increase. Bilirubin levels tend to be slightly elevated but may rise more quickly in a hemolytic crisis. The bilirubin also may increase if there are gallstones present which block the flow of bilirubin from the liver.
What are the possible complications of HS?
Many patients with HS have bone marrow that is able to compensate enough so that the child is only mildly anemic and does not have major symptoms. Whether your child has mild, moderate or severe HS, there are a number of HS complications that parents should be aware of:
- Aplastic crises. This type of crisis often is associated with viral infections. The bone marrow is suppressed by the viral infection and the number of new red blood cells produced is decreased. The patient's red blood cells are destroyed at their usual rate and this results in a worsening of the anemia. In this type of crisis the patient with HS may quickly develop severe anemia and may require a blood transfusion. Symptoms of an aplastic crisis may include increasing pallor (paleness), decreased energy and decreased appetite.
- Hemolytic crises. This is the most frequent type of crisis that occurs in patients with HS. It is caused most often by a viral infection and results when there is a sudden increase in red blood cell destruction. It is rarely severe but will result in worsening anemia, increasing jaundice, enlargement of the spleen and an increased reticulocyte count. Occasionally this type of crisis requires a blood transfusion.
- Gallstones. The excessive production of bilirubin from the destroyed red blood cells can lead to the formation of bilirubin gallstones. These may collect in the bile ducts or gall bladder and cause irritation or obstruction of bile flow. This is called a "gall bladder attack" or cholecystitis. These gallstones may occur in infancy but typically appear in adolescence and young adult life. Five percent of children under 10 with HS have gallstones. Studies have shown that approximately 50% of patients with HS who are between the ages of 10 and 30 years have gallstones. Over the age of 30 years the incidence continues to rise so that by age 50 almost all patients with HS have had gallstones.
- Other health issues. Severe HS has been associated with short stature, delayed sexual maturation, changes in the growth of facial bones, gout, leg ulcers and extramedullary hematopoieses. Extramedullary hematopoiesis is the growth of bone marrow tissue in organs of the body outside of the bone marrow. All of these conditions are rare but can be treated by a splenectomy (removal of the spleen.)
How is HS treated?
In most patients with HS, no specific therapy is needed other than monitoring for anemia and watching for signs and symptoms of an aplastic crisis, a hemolytic crisis, and/or gallstones.
In some patients who have severe anemia or other complications, a splenectomy (surgical removal of the spleen) is recommended. This can end the destruction of red blood cells, i.e., following a splenectomy, most patients with HS will have a normal levels of hemoglobin and bilirubin. Splenectomy also prevents aplastic and hemolytic crises and significantly decreases the risk of gallstones.
However, there are many potential complications to a splenectomy. Patients who have had a splenectomy are at greater risk for very serious bacterial infections. The exact incidence of infection is unknown but more recent studies have shown it to be 1 percent to 2 percent. These infections are more common in children less than five years of age. For this reason, splenectomy for HS is usually delayed until after age five. Vaccinations and use of preventive antibiotics decrease this risk but will not absolutely prevent infections.
It is recommended that all patients who are going to have a splenectomy have a hemophilus influenza B, pneumococcus and meningococcus vaccinations prior to the splenectomy. The pneumococcus vaccination should be repeated every five years. Prophylactic antibiotics are recommended for at least three years following splenectomy and may be recommended for a longer period of time. The most important point to remember is that any fever or illness in a child who's had a splenectomy should be promptly evaluated by a physician.
Other potential complications of a splenectomy include bleeding (during or immediately following the surgery), pancreatitis and/or intestinal obstruction. Long-term potential complications include infection, portal vein thrombosis and intestinal obstruction. Some patients who have had a splenectomy may have a high platelet count. In adult life, this may increase the risk of atherosclerotic heart disease; many adults who have had a splenectomy are on a low-dose aspirin therapy regimen.
More recently, some evidence has pointed to a connection between splenectomy for HS and the development of venous thrombosis (blood clots.) In some cases, the high platelet count has been suggested as contributing to the problem of venous thrombosis but, in other patients, that connection is less clear. In some patients, pulmonary hypertension has developed related to blood clots in the lung.
Pulmonary hypertension is an apparently uncommon but potentially fatal complication that has been described anywhere from eight to 50+ years following a splenectomy. It is unknown if there are other factors that may contribute to the development of this complication and at this time there are no specific recommendations for prevention or routine testing for this problem.
About treatment for hereditary spherocytosis at Children's
Children's Cancer and Blood Disorders program achieves outcomes that rank among the top national programs and cares for more than two-thirds of Minnesota children and adolescents with blood disorders. In the program, families coping with HS have access to the newest and most promising treatments and receive care spearheaded and coordinated by a board-certified hematologist/oncologist.
If you are a family member looking for a Children's hematologist or oncologist or wanting to schedule an appointment, call the outpatient clinic at Children's – Minneapolis at (612) 813-5940
If you are a health professional looking for consultation or referral information, please call Children's Physician Access at 1-866-755-2121 (toll-free).