Anemia- hereditary spherocytic hemolytic

December 31, 2014

Synonyms

Overview

Hereditary spherocytic hemolytic anemia is a rare blood disorder characterized by defects within red blood cells (intracorpuscular) that result in a shortened survival time for these cells. Red blood cells (erythrocytes) normally circulate for a few months and when they die off are replaced by new erythrocytes. However, in hereditary spherocytic hemolytic anemia, the cells die prematurely. They also have low amounts of fats (lipid) in the cell membranes and an abnormally small amount of surface area. The red blood cells are sphere-shaped (spherocytic) making it difficult for them to pass through the spleen, resulting in the early destruction of these cells (hemolysis). The sphere shape of the red blood cells is the hallmark of this disorder, and this abnormality may be identified under a microscope. Hereditary spherocytic hemolytic anemia is caused by an inherited metabolic defect.

Symptoms

Symptoms of hereditary spherocytic hemolytic anemia may include excessive tiredness and a moderate persistent yellow appearance to the skin (jaundice). The onset of puberty may be delayed in children with this disorder. Some children may experience abdominal discomfort and have an abnormally enlarged spleen (splenomegaly).

An infection is the most common cause of the temporary failure of the bone marrow to produce blood components (aplastic crisis) in people with hereditary spherocytic hemolytic anemia. This crisis results in a temporary deficiency of red blood cell production. Trauma or pregnancy may make the aplastic crisis worse. Symptoms of an aplastic crisis may include fever, headache, abdominal pain, profound loss of appetite (anorexia), vomiting, and fatigue. Children who are experiencing an aplastic crisis may also have nose bleeds (epistaxis).

Occasionally children with hereditary spherocytic hemolytic anemia have an abnormally enlarged liver (hepatomegaly), stones in the gall bladder (cholelithiasis), and/or leg ulcers. In some cases deformities of the anatomy are present at birth and may include more than the normal number of fingers and/or toes (polydactylism), and/or a "tower-shaped" skull.

Hemolytic anemias, including hereditary spherocytic hemolytic anemia, have two distinct laboratory findings: a reduction in the life span of red blood cells and the retention of iron within the body particularly in those cells that have the ability to dispose of wastes and toxins (reticuloendothelial system or RES). In all hemolytic anemias, there is excessive destruction of red blood cells.

Acholuric Jaundice
Chronic Acholuric Jaundice
Congenital Hemolytic Anemia
Congenital Hemolytic Jaundice
Congenital Spherocytic Anemia
Hereditary Spherocytosis
HS
Icterus (Chronic Familial)
Minkowski-Chauffard Syndrome
SPH2
Spherocytic Anemia
Spherocytosis

Causes

Usually people with hereditary spherocytic hemolytic anemia have a family history of anemia, jaundice, or spleen enlargement (splenomegaly). At times, other family members can be identified with this disorder, but in other cases people with hereditary spherocytic hemolytic anemia may have no family history of the disorder that can be traced.

The typical, common form of inheritance is autosomal dominant, although there are rare occurrences of autosomal-recessive forms.

Most cases of the autosomal-dominant form are due to defects of a protein known as ankyrin. These cases are associated with a gene located on the short arm of chromosome 8 (8p11.2).

Diagnosis

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Prognosis

Overall, the long-term outlook (prognosis) for people with hereditary spherocytosis (HS) is usually good with treatment. However, it may depend on the severity of the condition in each person. HS is often classified as being mild, moderate or severe. People with very mild HS may not have any signs or symptoms unless an environmental "trigger" causes symptom onset. In many cases, no specific therapy is needed other than monitoring for anemia and watching for signs and symptoms. Moderately and severely affected people are likely to benefit from splenectomy. Most people who undergo splenectomy are able to maintain a normal hemoglobin level. However, people with severe HS may remain anemic post-splenectomy, and may need blood transfusions during an infection.

Information about life expectancy in the medical literature appears to be limited. However, we are not aware of reports that state that life expectancy is known to be significantly shortened in people without other medical problems who are managed appropriately. In all people who undergo splenectomy, there is a lifelong, increased risk of developing a life-threatening infection (sepsis). 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. Fortunately, taking certain precautions can reduce this risk and can prevent minor infections from becoming life-threatening.

Treatment

Hereditary spherocytic hemolytic anemia usually has a long, chronic course. The standard treatment is folic acid replacement so that adequate stores will be available to maintain increased red cell production. Red cell transfusions may be needed for times of profound anemia during aplastic crisis, or on a chronic basis for the severe forms. For severe neonatal jaundice, exchange transfusion may be required.

If patients have moderate to severe anemia and/or chronic jaundice, removal of the spleen (splenectomy) will usually nearly eliminate the symptoms of the autosomal-dominant condition and improve the symptoms in the more severe recessive forms. Surgical removal of the gallbladder (cholecystectomy) may be required to address the symptoms related to the gallstones.

Genetic counseling will be of benefit for families affected by hereditary spherocytic hemolytic anemia. Other treatment is symptomatic and supportive.

Splenectomy, after appropriate vaccination, is the only specific treatment for either disorder but is rarely needed. It is indicated in patients < 45 yr with Hb persistently < 10 g, jaundice or biliary colic, or persistent aplastic crisis. If the gallbladder has stones or other evidence of cholestasis, it should be removed during splenectomy. Although spherocytosis persists after splenectomy, the cells survive longer in the circulation. Symptoms, anemia, and reticulocytosis usually resolve. However, RBC fragility remains high.