Autoimmune Hemolytic Anemia
Disease Details
Family Health Simplified
- Description
- Autoimmune hemolytic anemia is a condition where the immune system mistakenly attacks and destroys red blood cells, leading to anemia.
- Type
- Autoimmune hemolytic anemia (AIHA) is primarily an acquired disorder, meaning it is not typically inherited through genetic transmission. It occurs when the immune system produces antibodies that mistakenly target and destroy red blood cells.
- Signs And Symptoms
- Symptoms of AIHA may be due to the underlying anemia; including shortness of breath or dyspnea, fatigue, headache, muscle weakness and pallor. In cold agglutinin disease (cold antibody type), agglutination and impaired passage of red blood cells through capillaries in the extremities causes acrocyanosis and Raynaud phenomenon with a rare complication of gangreneSpherocytes are found in immunologically mediated hemolytic anemias. Signs of hemolysis that are present in AIHA include low hemoglobin (blood count), alterations in levels of cell markers of hemolysis; including elevated lactate dehydrogenase (LDH), decreased haptoglobin and elevated unconjugated bilirubin. Reticulocytosis, or an increase in circulating immature red blood cells, may be seen.
- Prognosis
- Autoimmune hemolytic anemia (AIHA) prognosis varies based on the underlying cause, patient’s age, and response to treatment. Generally, with timely and appropriate management, many patients can achieve remission or stable long-term control. However, some may experience chronic or recurrent episodes. Early diagnosis and tailored treatment can significantly improve outcomes.
- Onset
- Autoimmune hemolytic anemia can have a sudden (acute) onset or develop gradually over time. The exact timing can vary significantly among individuals. In some cases, it may manifest rapidly over a few days, while in others, symptoms might emerge and progress over weeks or months.
- Prevalence
- Autoimmune hemolytic anemia (AIHA) is a rare condition, with an estimated prevalence of about 1 to 3 cases per 100,000 people annually. The actual prevalence can vary depending on the specific type of AIHA (warm or cold agglutinin disease) and the population studied.
- Epidemiology
- Autoimmune Hemolytic Anemia (AIHA) is a rare condition, with an estimated incidence of 1-3 cases per 100,000 people annually. It can affect individuals of all ages but is more commonly diagnosed in adults and older individuals. The condition tends to be slightly more prevalent in females than in males. AIHA can be primary (idiopathic) or secondary to other diseases such as infections, autoimmune disorders, or certain medications.
- Intractability
- Autoimmune hemolytic anemia (AIHA) can be challenging to treat, but it is not necessarily intractable. The disease's severity and response to treatment can vary widely among patients. Common treatments include corticosteroids, immunosuppressive drugs, and in some cases, splenectomy. Many patients respond well to these treatments, but some may experience recurrent or chronic symptoms. Therefore, while AIHA can be difficult to manage, it is not universally intractable.
- Disease Severity
- Autoimmune hemolytic anemia (AIHA) severity can vary widely. In mild cases, individuals may experience only minor symptoms and require minimal treatment, while in severe cases, the condition can lead to life-threatening complications such as severe anemia, jaundice, and organ damage. Severity depends on the extent of red blood cell destruction and the body's ability to produce new red blood cells.
- Healthcare Professionals
- Disease Ontology ID - DOID:718
- Pathophysiology
- AIHA can be caused by a number of different classes of antibody, with IgG and IgM antibodies being the main causative classes. Depending on which is involved, the pathology will differ. IgG is not very effective at activating complement and effectively binds the Fc receptor (FcR) of phagocytic cells, AIHA involving IgG is generally characterized by phagocytosis of RBCs. IgM is a potent activator of the classical complement pathway, thus, AIHA involving IgM is characterized by complement-mediated lysis of RBCs. IgM also leads to phagocytosis of RBCs however, because phagocytic cells have receptors for the bound complement (rather than FcRs as in IgG AIHA). In general, IgG AIHA takes place in the spleen, whereas IgM AIHA takes place in Kupffer cells – phagocytic cells of the liver. Phagocytic AIHA is termed extravascular, whereas complement-mediated lysis of RBCs is termed intravascular AIHA. In order for intravascular AIHA to be recognizable, it requires overwhelming complement activation, therefore most AIHA is extravascular – be it IgG- or IgM-mediated.AIHA cannot be attributed to any single autoantibody. To determine the autoantibody or autoantibodies present in a patient, the Coombs test, also known as the antiglobulin test, is performed. There are two types of Coombs tests, direct and indirect; more commonly, the direct antiglobulin test (DAT) is used. Classification of the antibodies is based on their activity at different temperatures and their etiology. Antibodies with high activity at physiological temperature (approximately 37 °C) are termed warm autoantibodies. Cold autoantibodies act best at temperatures of 0–4 °C. Patients with cold-type AIHA, therefore, have higher disease activity when body temperature falls into a hypothermic state. Usually, the antibody becomes active when it reaches the limbs, at which point it opsonizes RBCs. When these RBCs return to central regions, they are damaged by complement. Patients may present with one or both types of autoantibodies; if both are present, the disease is termed "mixed-type" AIHA.When DAT is performed, the typical presentations of AIHA are as follows. Warm-type AIHA shows a positive reaction with antisera to IgG antibodies with or without complement activation. Cases may also arise with complement alone or with IgA, IgM or a combination of these three antibody classes and complement. Cold-type AIHA usually reacts with antisera to complement and occasionally to the above antibodies. This is the case in both cold agglutinin disease and cold paroxysmal hematuria. In general, mixed warm and cold AIHA shows a positive reaction to IgG and complement, sometimes IgG alone, and sometimes complement alone. Mixed-type can, like the others, present unusually with positive reactions to other antisera.
- Carrier Status
- Autoimmune hemolytic anemia (AIHA) is not a genetic condition caused by a single gene mutation, so there is no carrier status for it. This type of anemia results from the immune system mistakenly attacking the body's own red blood cells. Factors contributing to AIHA include underlying autoimmune disorders, infections, certain medications, and malignancies, but it is not something one can "carry" like a genetic disease.
- Mechanism
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Autoimmune hemolytic anemia (AIHA) is a condition where the immune system mistakenly attacks and destroys red blood cells, leading to anemia.
### Mechanism:
In AIHA, the immune system produces autoantibodies that bind to antigens on the surface of red blood cells. This binding causes the destruction of these cells through two primary mechanisms:
1. **Extravascular Hemolysis:** The antibody-coated red blood cells are recognized and phagocytosed by macrophages primarily in the spleen and liver.
2. **Intravascular Hemolysis:** Less commonly, the binding of antibodies activates the complement system, leading to the lysis of red blood cells within blood vessels.
### Molecular Mechanisms:
1. **Autoantibodies Production:** In AIHA, B cells produce autoantibodies (mainly IgG or IgM) that target proteins on the red blood cell membrane.
- **IgG-mediated:** IgG antibodies bind to red blood cell antigens, marking them for destruction by splenic macrophages (extravascular hemolysis).
- **IgM-mediated:** IgM antibodies can activate the complement system more efficiently, leading to either intravascular hemolysis or opsonization and subsequent removal by the liver.
2. **Complement Activation:** When IgM antibodies bind to red blood cells, they activate the classical complement pathway. Complement components (such as C3b and C5b-9) form membrane attack complexes that cause cell lysis or opsonization, enhancing phagocytosis by macrophages.
3. **Fc Receptor Engagement:** Macrophages in the spleen and liver possess Fc receptors that bind to the Fc region of IgG-coated red blood cells, facilitating their uptake and destruction.
4. **Regulatory Mechanisms Failure:** Normally, regulatory mechanisms prevent the immune system from attacking self-tissues. In AIHA, a failure of these regulatory pathways (e.g., regulatory T cells dysfunction or inadequate tolerance mechanisms) allows autoantibody production.
Understanding these molecular mechanisms provides insight into potential therapeutic targets, such as inhibiting Fc receptor function, blocking complement activation, or modulating B cell activity to reduce autoantibody production. - Treatment
- Steroids are the first line treatment in warm AIHA; with oral prednisone achieving an 80% initial response rate, with a 30-40% sustained remission rate at 1 year. Steroids may be decreased at 3 weeks and tapered at 3–6 months depending on the response. Rituximab may be added to initial management to increase the response rate, or it may be used in cases of severe disease such as IgA mediated warm AIHA, mixed AIHA, Evans syndrome or in cases of high hemolysis levels). If a response cannot be achieved with steroids or rituximab, splenectomy can be done. Other third line options, that are less studied, include azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil and bortezomib. The treatments for secondary warm AIHA are generally the same as primary warm AIHA, but with the addition of treating the underlying disease if possible.Steroids are not indicated in the treatment of cold agglutinin disease due to low response rates. Cases of cold agglutinin disease with mild anemia with limited and compensated hemolysis can be monitored with adjunct supportive care (such as avoidance of cold exposure or thermal protection to prevent against hemolysis). Rituximab is used to treat pathogenic B-cell clones in cold agglutinin disease with response rates of 45-60%. Relapses are common upon discontinuation of rituximab, but the medication can be restarted to achieve subsequent remission. Rituximab can be combined with bendamustine to achieve a 71% overall and 40% complete response rate with an increased response seen with prolonged therapy (with a time to best response at a median of 30 months) due to the drugs' effect on long lived plasma cells. Splenectomy is less efficacious in cold agglutinin disease.Special considerations are required when treating people with AIHA using blood transfusion. In cold agglutinin disease; the patient and the extremity should be kept warm during transfusion to prevent agglutination and hemolysis of the donor and patient red blood cells. In warm AIHA; cross-matching of blood will show incompatibility so it is recommended to perform a bedside in vivo compatibility test prior to infusion. Erythropoietin (EPO) has been shown to increase hemoglobin levels in cold and warm AIHA.
- Compassionate Use Treatment
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For Autoimmune Hemolytic Anemia (AIHA):
**Compassionate Use Treatment:**
Compassionate use, also known as expanded access, allows patients with serious or life-threatening conditions, including AIHA, to access investigational treatments outside of clinical trials. This option is typically considered when conventional treatments have failed, and the patient has no other medical options. Specific drugs and biologics considered under compassionate use need to be approved by the FDA or relevant authorities on a case-by-case basis.
**Off-label or Experimental Treatments:**
1. **Rituximab** - Originally approved for non-Hodgkin lymphoma, it is frequently used off-label for AIHA, particularly for treating refractory or severe cases.
2. **Eltrombopag or Romiplostim** - Thrombopoietin receptor agonists primarily used for immune thrombocytopenia, they have been explored off-label for AIHA to stimulate platelet production.
3. **Eculizumab** - An experimental treatment targeting the complement system, which has been investigated for cases of AIHA involving complement-mediated hemolysis.
4. **Cyclophosphamide or other immunosuppressants** - Used off-label to suppress the immune response in severe, refractory AIHA cases.
These treatments are typically considered when first-line therapies, such as corticosteroids or splenectomy, are ineffective or unsuitable. - Lifestyle Recommendations
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Lifestyle recommendations for autoimmune hemolytic anemia (AIHA) focus on managing symptoms and supporting overall health. Here are some recommendations:
1. **Balanced Diet**: Consume a diet rich in fruits, vegetables, lean proteins, and whole grains to support overall health and immune function.
2. **Hydration**: Stay well-hydrated to help kidneys filter the breakdown products of red blood cells effectively.
3. **Avoid Triggers**: Identify and avoid known triggers that may exacerbate hemolysis, such as certain medications or infections.
4. **Rest**: Ensure adequate rest to combat fatigue and reduce stress on the body.
5. **Regular Check-ups**: Schedule regular medical appointments to monitor blood counts and manage the condition effectively.
6. **Vaccinations**: Stay up-to-date with vaccinations, especially for influenza and pneumococcal infections, to reduce the risk of infections that can trigger hemolysis.
7. **Exercise**: Engage in light to moderate exercise as tolerated to maintain physical fitness without overexertion.
8. **Avoid Extreme Temperatures**: Protect yourself from extreme cold or heat, as temperature extremes can sometimes exacerbate hemolytic processes.
9. **Stress Management**: Practice stress-reducing techniques such as meditation, yoga, or deep-breathing exercises to help manage emotional well-being.
Consult with a healthcare provider for personalized advice tailored to your specific condition and needs. - Medication
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For autoimmune hemolytic anemia (AIHA), medications commonly used include:
1. **Corticosteroids**: Prednisone is often the first line of treatment to reduce the immune system's attack on red blood cells.
2. **Immunosuppressants**: Drugs such as rituximab, azathioprine, or cyclophosphamide may be used if corticosteroids are ineffective.
3. **Intravenous Immunoglobulin (IVIG)**: This can be administered to reduce the immune response and decrease red blood cell destruction.
4. **Blood transfusions**: These may be necessary in severe cases to maintain adequate red blood cell levels.
Treatment plans vary based on the severity of the condition and the patient’s response to initial therapies. - Repurposable Drugs
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Autoimmune hemolytic anemia (AIHA) is a condition where the immune system destroys red blood cells, leading to anemia. Repurposable drugs for AIHA may include:
1. **Rituximab**: Originally used for lymphoma, this monoclonal antibody can help reduce the activity of the immune system.
2. **Mycophenolate mofetil (CellCept)**: An immunosuppressant initially used to prevent organ transplant rejection.
3. **Cyclosporine**: Another immunosuppressant commonly used in transplant patients but can also be used to control autoimmune responses.
4. **Azathioprine**: Used for various autoimmune diseases, this drug suppresses the immune system to reduce the destruction of red blood cells.
5. **Bortezomib**: Primarily used for multiple myeloma, it can be effective in refractory cases of AIHA.
Consulting with a healthcare provider is essential before starting any treatment. - Metabolites
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Autoimmune hemolytic anemia (AIHA) involves the destruction of red blood cells (RBCs) due to an immune response against them. Key metabolites to consider in AIHA include:
1. **Bilirubin**: Elevated levels due to increased RBC breakdown.
2. **Lactate dehydrogenase (LDH)**: Increased levels, indicating cell damage and lysis.
3. **Haptoglobin**: Decreased levels, as it binds to free hemoglobin released from destroyed RBCs.
4. **Reticulocytes**: Elevated, reflecting the bone marrow's response to anemia by producing more immature RBCs.
These metabolites are crucial for diagnosing and monitoring the progression of AIHA. - Nutraceuticals
- There is currently no robust scientific evidence directly supporting the use of specific nutraceuticals for the treatment of autoimmune hemolytic anemia (AIHA). Management typically involves immunosuppressive therapy, corticosteroids, and other pharmacologic treatments. Always consult healthcare professionals before considering any alternative or supplemental therapies.
- Peptides
- In autoimmune hemolytic anemia (AIHA), the immune system mistakenly attacks and destroys red blood cells. Peptides are not typically the primary treatment modality for AIHA, but they may be studied for their potential to modulate immune responses. Nanotechnology (nan) is being explored in various medical fields, including autoimmune diseases, for its potential to deliver drugs more effectively to the site of action, reduce side effects, and improve treatment outcomes. However, specific nanotechnology applications for AIHA are still in the research phase and not yet standard treatment.