What is the most common cause of hemolysis? Understanding the various factors

October 1, 2025 •

4 min read

Every day, the body's spleen and liver naturally break down billions of red blood cells to make way for new ones. However, the most common cause of hemolysis, or premature red blood cell destruction, varies significantly depending on the context—whether it occurs in a laboratory sample or inside the body due to a medical condition.

Quick Summary

Hemolysis, the premature destruction of red blood cells, can stem from procedural errors in lab specimens or underlying medical issues inside the body. Clinically, causes are categorized as acquired (like autoimmune disorders) or inherited (like sickle cell disease), each with specific risk factors and symptoms.

Key Points

Cause depends on context: The most common cause of hemolysis is not a disease but rather procedural errors during blood specimen collection and handling in a lab setting.
Autoimmunity is a leading clinical cause: Within the body, autoimmune hemolytic anemia (AIHA) is the most common acquired cause in adults, where the immune system attacks red blood cells.
Hereditary conditions are significant: Inherited disorders like hereditary spherocytosis, sickle cell disease, and thalassemia are frequent causes of chronic hemolysis, especially in specific populations.
Infections can trigger hemolysis: Pathogens such as the malaria parasite can directly destroy red blood cells, while toxins from certain bacteria like E. coli can cause hemolytic uremic syndrome.
Symptoms indicate hemolysis: Common signs of excessive hemolysis and resulting hemolytic anemia include jaundice, fatigue, pale skin, and an enlarged spleen or liver.
Diagnosis is crucial: Identifying the specific cause through lab tests like a complete blood count (CBC), Coombs test, or hemoglobin electrophoresis is necessary for effective treatment.
Management is cause-specific: Treatment options range from addressing underlying infections or disorders to corticosteroids, blood transfusions, or splenectomy in severe cases.

Understanding Hemolysis

Hemolysis is the process of red blood cell destruction, also known as erythrocytes. While a routine part of the body's life cycle, excessive or premature hemolysis can lead to a shortage of red blood cells, a condition called hemolytic anemia. Red blood cells transport oxygen throughout the body, so when they break down too quickly, it can impair the delivery of oxygen to organs and tissues. The causes can be broadly divided into issues that arise in a clinical laboratory setting (in vitro) and medical conditions occurring within the body (in vivo).

The Most Common Cause: Context Matters

Answering what is the most common cause of hemolysis? requires clarifying the setting. The most frequent cause of hemolysis overall is not a disease but rather an error that occurs when a blood sample is collected or handled in a clinical laboratory. When considering clinical causes within the human body, the answer becomes more complex, varying between inherited and acquired conditions.

In the Clinical Lab (In Vitro)

In a laboratory context, hemolysis refers to the rupture of red blood cells in a collected blood specimen, which can interfere with the accuracy of diagnostic tests. The most common procedural errors include:

Residual alcohol: Not allowing the skin puncture site to dry completely before collecting blood.
Excessive mixing: Shaking the blood collection tube too vigorously after collection.
Needle gauge mismatch: Using a small-diameter needle with a large-volume tube, which can damage the red blood cells as they are drawn.
Improper centrifugation: Spinning the blood specimen at incorrect speeds or times.

In the Body (In Vivo)

When hemolysis occurs inside the body, it points to an underlying medical issue. These causes are categorized as either intrinsic, a defect within the red blood cell itself, or extrinsic, an external factor damaging healthy red blood cells. Among acquired, or extrinsic, causes, autoimmune hemolytic anemia (AIHA) is considered the most common. However, specific inherited conditions are very prevalent in certain populations and can be the most frequent cause in those groups.

Common Medical Causes of Hemolysis

Medical causes of hemolysis are diverse, and identifying the specific reason is crucial for effective treatment. These are typically organized into acquired (extrinsic) and hereditary (intrinsic) categories.

Acquired (Extrinsic) Causes

These conditions develop after birth and are not inherited. They involve external factors or the body's own immune system targeting healthy red blood cells.

Autoimmune Hemolytic Anemia (AIHA): This is the most common acquired cause in adults. The immune system produces antibodies that attack and destroy red blood cells prematurely. AIHA can be primary (idiopathic) or secondary to conditions such as:
- Autoimmune diseases like lupus or rheumatoid arthritis
- Blood cancers, including chronic lymphocytic leukemia and lymphoma
- Infections such as Mycoplasma pneumoniae, HIV, or hepatitis
Infections: Besides triggering AIHA, certain infections can directly damage red blood cells. Malaria, caused by a parasite that invades and ruptures red blood cells, is a well-known example. In children under five, infection with toxin-producing E. coli is the most common cause of hemolytic uremic syndrome (HUS), a condition that causes hemolysis.
Medications: Some drugs can induce immune-mediated hemolysis. Common examples include penicillin, certain cephalosporins, and quinidine.
Mechanical Damage: Physical trauma to red blood cells can occur from prosthetic heart valves or other cardiovascular devices.

Hereditary (Intrinsic) Causes

These are genetic disorders that cause defects in the red blood cells themselves, shortening their lifespan.

Hereditary Spherocytosis (HS): This is the most common inherited cause of hemolytic anemia, particularly in people of Northern European descent. It causes red blood cells to be abnormally spherical and fragile, leading to their destruction primarily in the spleen.
Sickle Cell Anemia: This is a disorder of hemoglobin, where red blood cells take on a sickle shape. These rigid, sticky cells can block blood flow and are destroyed prematurely. It is a very common cause of hemolysis, especially in specific populations.
Thalassemia: This condition involves defects in hemoglobin production, which causes the body to produce fewer red blood cells and those that are produced have a shorter lifespan.
G6PD Deficiency: A deficiency in the enzyme glucose-6-phosphate dehydrogenase makes red blood cells susceptible to damage from oxidative stress, often triggered by certain foods (fava beans) or medications.

Acquired vs. Hereditary Hemolysis


Feature	Acquired Hemolysis	Hereditary Hemolysis
Cause	External factors or immune system attacking otherwise normal red blood cells.	Genetic defects within the red blood cell itself.
Onset	Develops at any point after birth.	Present from birth, though symptoms may appear later in life.
Examples	Autoimmune hemolytic anemia, drug-induced hemolysis, infections, mechanical trauma.	Hereditary spherocytosis, sickle cell anemia, thalassemia, G6PD deficiency.
Diagnosis	Often diagnosed with a direct antiglobulin test (Coombs test) to check for antibodies on red blood cells.	Genetic studies, hemoglobin electrophoresis, and specialized red blood cell membrane tests.
Management	Treatment focuses on addressing the underlying cause, such as managing the autoimmune disorder or removing the offending drug.	Management involves addressing symptoms, supplementing with folic acid, and sometimes a splenectomy in severe cases.

Conclusion

While a variety of factors can cause the breakdown of red blood cells, understanding the specific cause is critical for proper diagnosis and treatment. In clinical practice, distinguishing between procedural lab errors and true medical conditions is the first step. For conditions occurring within the body, differentiating between acquired factors like autoimmune disorders and hereditary conditions such as sickle cell disease or hereditary spherocytosis guides the appropriate therapeutic approach. If you experience symptoms such as fatigue, jaundice, or dark urine, consulting a healthcare professional is essential for determining the underlying cause of hemolysis. For further information, the Cleveland Clinic offers comprehensive resources on the topic.

Note: This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.

Source: https://my.clevelandclinic.org/health/diseases/24108-hemolysis

Frequently Asked Questions

The most common cause of hemolysis in a lab-collected blood specimen is procedural error during collection, handling, or processing, such as vigorous mixing or improper centrifugation.

Autoimmune hemolytic anemia (AIHA) is an acquired condition where the immune system mistakenly creates antibodies that attack and destroy the body's own red blood cells prematurely.

Yes, inherited causes of hemolysis (intrinsic causes) include genetic disorders like hereditary spherocytosis, sickle cell anemia, and thalassemia, which result in defective red blood cells with a shorter lifespan.

Yes, infections can cause hemolysis. Some pathogens, like the malaria parasite, directly damage red blood cells, while others, like certain strains of E. coli, can release toxins that cause a severe hemolytic reaction.

Symptoms of excessive hemolysis often lead to hemolytic anemia and include fatigue, pale skin, jaundice (yellowing of the skin and eyes), dark urine, and an enlarged spleen.

Diagnosis of the specific cause of hemolysis involves a combination of medical history, physical examination, and various blood tests, including a complete blood count (CBC), direct antiglobulin test (Coombs test), and in some cases, genetic testing or hemoglobin electrophoresis.

While mild hemolysis may not require intervention, acute, severe cases (known as a hemolytic crisis) can be life-threatening and require immediate medical attention, potentially including a hospital stay, oxygen, and blood transfusions.