Hereditary Spherocytosis: Abnormally Morphed RBCs

Introduction

Hereditary spherocytosis (HS) is a congenital disorder (identified in 1871)that affects the surface of the red blood cells and leads to alterations in their shape. It affects nearly 1 in 2,000 to 5,000 people in the world. The genetic mutations in the gene coding for the structural membrane protein of the red blood cells lead to alterations in the structure of red blood cells, from disk-like shapes to spherical cells. Thus, morphological alterations in the red blood cells interfere with their ability to circulate in the body and also result in the cells rupturing under mechanical or osmotic stress. These dysfunctional red blood cells are degraded in the spleen, causing a shortage of red blood cells in circulation and hemolytic anemia.

What Is Hereditary Spherocytosis?

Hereditary spherocytosis (HS) is a genetic disorder that affects the surface membrane of red blood cells. It causes alterations in the structure of the red blood cells from disc-shaped to spherical shape, making them less flexible than normal cells. The irregularly shaped red blood cells are broken down in the spleen resulting in hemolytic anemia. Normal red blood cells usually live up to 120 days, but in the case of red blood cells with hereditary spherocytosis, the life span is nearly 10 to 30 days.

What Are the Causes of Hereditary Spherocytosis?

Hereditary spherocytosis is a genetic condition. Nearly 75 percent of people with hereditary spherocytosis inherit it as an autosomal dominant condition. Individuals inherit hereditary spherocytosis from their parents. Thus only one copy of the gene from the parent is enough to cause the condition in offspring. Hereditary spherocytosis occurs due to various molecular defects involving the genes that code for proteins ankyrin, spectrin, protein 4.2, and brand 3 protein present in the cell membrane of red blood cells. These mutations cause alterations in the membrane proteins resulting in abnormal shape and functioning of red blood cells.

What Are the Symptoms of Hereditary Spherocytosis?

• Ataxia.

• Skin ulcer.

• Spontaneous hemolytic crisis.

• Abdominal distention.

• Anemia.

• Chills.

• Abdominal pain.

• Gout.

• Cholelithiasis.

• Growth delay.

• Jaundice.

• Myalgia.

• Splenomegaly.

• Reticulocytosis.

• Pallor.

• Muscle weakness.

• Spherocytosis.

• Restrictive cardiomyopathy.

• Maculopapular exanthema.

• Hypofibrinogenemia.

• Increased osmotic fragility of red cells.

• Hepatomegaly.

• Fatigue.

• Extramedullary hematopoiesis.

• Hypercoagulability.

How Does Hereditary Spherocytosis Affect Our Body?

People with hereditary spherocytosis experience hemolytic anemia along with other complications. It includes the following conditions:

• Enlarged Spleen - The spleen functions as a filter for damaged cells and blood and targets pathogens within the circulation. Normally the blood cells flow through the spleen within the narrow passages before entering the bloodstream. However, in hereditary spherocytosis, the spherical red blood cells (spherocytes) are trapped inside the spleen resulting in spleen expansion and splenomegaly. In hereditary spherocytosis, the affected individual develops splenomegaly or an enlarged spleen when the spleen is filled with spherocytes.

• Cardiovascular Complications - In hereditary spherocytosis, the altered spherical red blood cells (spherocytes) lack fluidity and plasma membrane compliance. Thus the lack of fluidity and compliance leads to the high viscosity of blood and the failure of red blood cells to deform when they are transiting through venules, arterioles, and capillary beds. Thus these vessels become smaller and congested. Alterations in the blood flow and viscosity may cause arterial cardiovascular diseases and deep vein thrombosis (DVT).

• Cellular Defects - A deficiency of membrane surface area is another defect in hereditary spherocytosis. Decreased surface area results in reduced mechanical compliance and plasma membrane integrity.

• Jaundice - High bilirubin levels are seen in patients with hereditary spherocytosis due to the increased breakdown of red blood cells in the body. It causes a yellowish pigmentation of mucous membranes, skin, and eyes.

• Gallstones - It is a common complication seen in hereditary spherocytosis patients. It is estimated that half of the hereditary spherocytosis patients have gallbladder stones. Gallbladder stones are hard, pebble-shaped deposits that are formed inside the gallbladder. These stones cause gallbladder ducts, abdominal pain, vomiting, and jaundice.

How Can We Diagnose Hereditary Spherocytosis?

The diagnosis of hereditary spherocytosis can be made through specific diagnostic tests. They are the following.

Laboratory Tests:

• Osmotic fragility test.

• Bilirubin level.

• Peripheral blood smear.

• Complete blood count.

• Coombs test.

• Acidified glycerol lysis test.

• Haptoglobin levels.

• Mean corpuscular hemoglobin concentration.

• Reticulocyte count.

• Eosin-5-maleimide binding test.

• Red blood cell distribution width.

• Lactate dehydrogenase levels.

• Plasma membrane electrophoresis.

Imaging Tests - Ultrasound is used to evaluate enlarged spleen and gallbladder stones.

What Are the Treatment Options for Hereditary Spherocytosis?

Treatment options for hereditary spherocytosis depend on the severity of the symptoms. Common treatment options for hereditary spherocytosis focus on preventing the damage of functional spherocytes produced by the erythrocyte progenitor cells in the bone marrow. The standard treatment options for hereditary spherocytosis are the following.

• Blood Transfusions - Anemia in patients with hereditary spherocytosis can be managed with blood transfusions.

• Iron Chelation Therapy - Iron overload occurs in people who recently had blood transfusions. Iron chelation therapy can be used to remove extra iron.

• Splenectomy - It is the surgical removal of the spleen. In patients with severe hereditary spherocytosis, the entire spleen is removed to stop extravascular hemolysis.

• Partial Splenectomy - A spleen section is removed to reduce the extravascular hemolysis.

• Gallbladder Removal - In patients with hereditary spherocytosis, gallbladder stones can be removed by surgical gallbladder removal (cholecystectomy).

• Phototherapy - It is used to treat jaundice in hereditary spherocytosis patients.

• Splenic Ablation - This is a non-operative technique for treating hereditary spherocytosis. Splenic ablation uses radiologic techniques to cauterize and coil blood vessels within the spleen.

What Are the Complications Associated with Hereditary Spherocytosis?

• Hemolytic crisis due to accelerated hemolysis.

• Leg ulcer.

• Folate deficiency due to increased requirements from bone marrow.

• An aplastic crisis with a fall in hemoglobin levels.

• Pigmented gallstones.

• Iron overload.

• Hyperglycemia.

• Cardiovascular complications.

• Deep vein thrombosis (DVT).

Conclusion

Hereditary spherocytosis is a genetic condition that affects the shape and function of red blood cells and causes hemolytic anemia. The affected individuals may have enlarged spleen, reduced red blood cell count, gallbladder stones, and yellowing of the skin and eyes. Specific laboratory tests can be used to evaluate the blood changes that may occur due to hereditary spherocytosis and to diagnose the condition. However, the treatment strategies for hereditary spherocytosis depend on the severity of the symptoms and associated complications.