What to Know About Osmotic Fragility Tests

Medically Reviewed by Dan Brennan, MD on June 29, 2021

An osmotic fragility test is a familiar test in the medical world, as it’s been used by health professionals for over 70 years. Because of this, it is considered a reliable way to check the health of red blood cells.

What Is An Osmotic Fragility Test?

An osmotic fragility test is a blood test which works to see if red blood cells have a tendency to break apart easily. 

Two conditions that can cause this to happen are called thalassemia and hereditary spherocytosis (HS). These conditions cause the red blood cells to be more likely to break and become a smaller size. 

Both thalassemia and HS may lead to hemolytic anemia. This is a type of anemia where you have a low count of red blood cells because your body is destroying them too fast. 

Osmotic Fragility Test Procedure

Preparation. There is no need to prepare in advance for an osmotic fragility test. 

When the test is being made, a blood sample is taken. This is done with a needle inserted into the skin to collect blood for testing in the laboratory. 

You may feel anywhere from a stinging sensation to a more noticeable pain the moment the needle is in the skin, but neither should last long. A bruise may appear where the needle was inserted. 

Risks. The risk in getting a blood test done is very small. Because people have different sized veins, the difficulties in taking a blood sample changes depending on the person. Even though there are very small risks when getting blood work done, they include:

  • Infection where the skin is broken
  • Several punctures when trying to find veins
  • Fainting or lightheadedness
  • Hematoma where clotted blood becomes a lump under your skin 
  • Excessive bleeding 

How the Test Works

Red blood cells are tested to see how likely they are to break, or rupture. This is done by putting them in a hemodiluted or hypotonic solution, which makes the cells swell and burst.

The edges of red blood cells are made of proteins which keep the cell together. If one of these proteins are weak, the edges are more likely to break when placed in the water-based solution.

An osmotic fragility test is often used to confirm red blood cell disorders. 

What the Test Results Mean

A normal test result is labeled as a negative result. Value ranges can be slightly different depending on when the laboratory the test was done, so if in doubt talk to a health professional about what the results mean. 

If you get an abnormal result, it could mean that you have one of the following.

  • Thalassemia is a blood condition that is passed through family genetics. It happens when DNA is mutated within cells. Hemoglobin is a protein in red blood cells that carries oxygen. It becomes less frequent because of this mutation. This can cause anemia. 
  • Hereditary spherocytosis (HS) is also a hereditary blood disorder that may cause anemia. Spherocytosis is when the shell, or membrane, of red blood cells are delicate. When the red blood cells pass through the spleen, they become smaller. Because of this, they have a significantly shorter lifespan than normal cells. With less cells to deliver oxygen to the body, the chance of anemia is probable.

Amenia. There are many different types of anemia, yet they are all similar in that it is a condition where there are not enough red blood cells to carry enough oxygen to your body. While symptoms of anemia are different depending on the type, it is common to experience:

  • Headaches
  • Dizziness or becoming lightheaded
  • Fatigue
  • Chest pain
  • Irregular heartbeats
  • Cold hands and feet
  • Weakness
  • Irregular breathing
  • Your skin may look yellow or pale 

Alternatives to the Osmotic Fragility Test

More recently, other tests called flow-cytometric tests are being used to diagnose HS. These tests are called eosin-5’-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT).

Studies show that both flow-cytometric tests gave more accurate results than a regular osmotic fragility test. Even better, a combination of EMA and FOFT tests are able to give a 100% correct diagnosis to patients. Because of this, it is predicted that these tests may become the standard method to test for hereditary spherocytosis in the future.

Other tests used to identify HS are mean corpuscular hemoglobin concentration, erythrocyte osmotic fragility, and cryohemolysis test. These tests are used because they are efficient and cost-effective.

WebMD Medical Reference



BLOOD RESEARCH: “Cryohemolysis, erythrocyte osmotic fragility, and supplementary hematimetric indices in the diagnosis of hereditary spherocytosis.”

International Journal of Laboratory Hematology: “Flow cytometric osmotic fragility test and eosin-5’-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.”

MAYO CLINIC: “Anemia.”; “Osmotic fragility testing.”; “Thalassemia.”

National Heart, Lung, and Blood Institute: “Hemolytic Anemia.”

Seattle Children’s: “Hereditary Spherocytosis.”

University of California San Francisco: "Osmotic fragility test."

© 2020 WebMD, LLC. All rights reserved.