Red Blood Cell Membrane Disorders: What to Know

Red blood cells (RBCs) are important cells for delivering oxygen throughout the body. When the membrane of these cells is defective, it produces a range of disorders.

RBCs contain hemoglobin, the oxygen-transporting protein. Hemoglobin releases carbon dioxide and picks up oxygen in the lungs. The heart then pumps this oxygen-rich blood through arteries that branch into smaller arteries until they reach the capillaries (tiny vessels that connect the arterial and venous systems).

In the capillaries, hemoglobin releases oxygen and picks up carbon dioxide. Blood returns through the venous system to the heart and lungs.

Normally, RBCs are in a biconcave disk shape—round with a dimple in the center on both the front and back. As RBCs move through capillaries, they need to be flexible and able to change shape to move through tiny vessels without breaking.

The RBC membrane is the structure surrounding the RBC that allows this to happen. The RBC membrane is made of two layers—a skeleton layer and a  lipid layer—that allow the shape of the RBC to change without breaking.

There are some disorders in which the RBC membrane does not function properly. This article will review the types and causes of RBC membrane disorders, the symptoms they may cause, as well as how they are diagnosed and treated. 

RBC Membrane Disorders Causes

RBC membrane disorders are hereditary conditions governed by genes that may be passed from parent to child. These genes must provide the correct instructions for developing the RBC membrane. Changes to these genes called mutations can result in abnormal RBC membranes. 

When the RBC membrane isn’t made properly, the RBCs may break apart as they go through small capillaries or other blood vessels. The abnormal RBCs may also gather in the spleen (an organ in the abdomen that filters the blood) and be destroyed.

As these cells are destroyed or unable to function normally, symptoms may begin to develop. While new red blood cells continue to be made in the bone marrow, the increased destruction may result in anemia (a low number of healthy red blood cells).

Symptoms

Although there are different types of RBC membrane disorders, they exhibit similar symptoms. 

The most common symptom is anemia. Anemia may cause the following symptoms:

• Feeling dizzy or weak
• Shortness of breath
• Pale skin
• Heart palpitations (fast, fluttering, or pounding heartbeat)
• Headache
• Feeling cold
• Chest pain

Other symptoms that may be experienced include:

• Enlarged spleen
• Yellowing of the skin (jaundice)
• Enlarged liver
• Fever
• Gallstones

Types 

Multiple types of RBC membrane disorders exist. 

Hereditary Spherocytosis

Hereditary spherocytosis (HS) is a condition in which RBCs are more spherical (like a ball) in shape (rather than shaped like a disk with a central dimple) and are more rigid than they should be. These cells are recognized by the immune system as abnormal and are taken to the spleen to be broken down. There are four forms, from mild to severe.

Hereditary Elliptocytosis

Instead of disk-shaped RBCs, the RBCs with hereditary elliptocytosis are elliptical (oval) in shape. Most people with elliptocytosis have few (if any) symptoms due to the disorder. There are some cases that can cause severe problems, however.

Hereditary Stomatocytosis

In hereditary stomatocytosis, abnormal hydration (amount of water in the cell) causes red blood cells to take on a mouth-shape area of central pallor (pale color), with accompanying changes in red cell membrane fragility. ("Stoma" means "mouth.")

Diagnosis

If an RBC membrane disorder is suspected, tests can be done to confirm the diagnosis. Taking a family medical history is useful, since these disorders run in families and, therefore, can be inherited.

Blood will be drawn for a complete blood count and blood smear. Lab professionals look at the size, shape, and number of the RBCs. These characteristics of the RBCs can help determine a possible diagnosis.

Other lab tests that may need to be taken to  make a diagnosis include:

• Bilirubin (this is a byproduct of the breakdown of red blood cells)
• Reticulocyte count (a count of young red blood cells)
• Hemoglobin electrophoresis (looks for variant types of hemoglobin)
• Iron studies
• Tests for immune-mediated hemolysis (red blood cell destruction)
• Genetic testing
• Bone marrow biopsy (a sample is analyzed by a pathologist to look for abnormalities in red and white blood cell production)

Treatment

The treatment of RBC membrane disorders is mostly focused on supportive measures, such as blood transfusions and supplementing nutrients that may be low, such as iron or folic acid. There is no treatment that can normalize the shape of RBCs as they are being formed.

Surgery to remove the spleen, called a splenectomy, may be needed for those who are experiencing a significant breakdown of RBCs in the spleen. Once the spleen is removed, the RBCs can live longer before being broken down.

Summary 

The RBC membrane is a structure in red blood cells that allows these cells to remain flexible. This is important as they move throughout the body and transport oxygen to the tissue and remove carbon dioxide.

When the RBC membrane structure isn’t formed correctly due to an inherited condition, the RBCs are not able to function as well as they should, and are often broken down. This can result in anemia. 

Treatment for RBC membrane disorders can include supportive interventions, like a blood transfusion or supplementing iron or folic acid. A splenectomy may be recommended to prevent the breakdown of RBCs by the spleen. 

A Word From Verywell 

Living with an inherited RBC membrane disorder may come with stress and worry. It may require routine blood checks to be sure blood levels aren’t too low. It may also mean you'll need surgery.

There can also be stress about having children and possibly passing the condition on to them. It is important to discuss these concerns with your healthcare team, to get advice and help when experiencing these things.