drug induced autoimmune hemolytic anemia

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    Drug-induced autoimmune hemolytic anemia, also known as Drug-induced immune hemolytic anemia (DIIHA), is a rare cause of hemolytic anemia. It is difficult to differentiate from other forms of anemia which can lead to delays in diagnosis and treatment. Many different types of antibiotics can cause DIIHA and discontinuing the offending medication is the first line of treatment. DIIHA has is estimated to affect one to two people per million worldwide.
    In some cases, a drug can cause the immune system to mistakenly think the body's own red blood cells are dangerous, foreign substances. Antibodies then develop against the red blood cells. The antibodies attach to red blood cells and cause them to break down too early. It is known that more than 150 drugs can cause this type of hemolytic anemia. The list includes:

    Cephalosporins (a class of antibiotics)
    Dapsone
    Levodopa
    Levofloxacin
    Methyldopa
    Nitrofurantoin
    Nonsteroidal anti-inflammatory drugs (NSAIDs) - among them, the commonly used Diclofenac and Ibuprofen
    Phenazopyridine (pyridium)
    Quinidine


    Signs and symptoms


    Initial symptoms of drug-induced autoimmune hemolytic anemia are typically vague and reflect mild, moderate, or severe anemia. Symptoms of DIIHA can manifest within hours to months of the initial drug exposure. DIIHA ranges in severity from severe intravascular hemolysis to milder presentations of extravascular hemolysis. Common symptoms of DIIHA are fatigue, shortness of breath, dizziness, bloody or dark urine, weakness, and palpitations. DIIHA will occasionally present as hemoglobinuria with chills, however this is quite rare. Patients with DIIHA may appear pale and have jaundice. Hepatomegaly, splenomegaly, and adenopathy have also been observed.
    When DIIHA is not recognized promptly it can have life-threatening complications such as hemolysis leading to shock, ischemia, acute respiratory distress syndrome, disseminated intravascular coagulation, and acute renal failure.


    Causes


    As of 2020 over 130 drugs have been reported to cause DIIHA. That number will continue to rise as new drugs are discovered. Antimicrobials are responsible for 42% of DIIHA cases, making them the most common cause. Nonsteroid anti-inflammatory drugs cause about 15% of cases and antineoplastic drugs cause around 11%.


    Mechanism


    The main mechanism of DIIHA is the development of antibodies. Drug-induced antibodies can be classified into two groups, drug-dependent antibodies and drug-independent autoantibodies. Drug-dependent antibodies are common in DIIHA. They require the offending drug to be present in order to bind and lyse cells.
    Drug-independent autoantibodies are a less common factor in DIIHA. Drug-independent autoantibodies are found in Drug-induced autoimmune hemolytic anemia because of beta-lactamase inhibitors and platinum-based chemotherapeutics. These autoantibodies can sometimes bind and react to red blood cells even in the absence of whatever drug triggered the anemia.


    Diagnosis


    Drug-induced autoimmune hemolytic anemia causes a significant drop in hemoglobin and hematocrit. Occasionally DIIHA can present with mild leukocytosis. In its earlier stages patients with DIIHA will have low reticulocytes. As HIIHA progresses reticulocytes increase leading to an elevated mean corpuscular volume. Indirect bilirubin and Lactate dehydrogenase become elevated. LFTs occasionally become elevated. In some cases, a peripheral blood smear may show schistocytes, anisocytosis, polychromasia, or poikilocytosis.
    Direct antiglobulin testing is the only way to confirm DIIHA. Direct antiglobulin testing can determine if complement C3 antibody and/or immunoglobulin G is bound to the red blood cell membrane. A positive direct antiglobulin test differentiates immune-mediated hemolytic anemia from a nonimmune-mediated cause. Other situations such as liver disease, post-transfusion or immunoglobulin administration, renal disease, and malignancy can cause a positive direct antiglobulin test. If both complement C3 Antibodies and immunoglobulin G are positive or if only immunoglobulin G is positive then warm antibody autoimmune hemolytic anemia must be considered as a differential diagnosis.


    Treatment


    An appropriate course of treatment for drug-induced autoimmune hemolytic anemia hasn't yet been established. Once DIIHA has been recognized, the patient must stop whatever drug caused the anemia in order to provide proper treatment. Patients should be given blood transfusions as needed. The use of thromboprophylaxis is encouraged because despite being anemic, patients are often hypercoagulable. Although corticosteroids have been used to treat DIIHA it is difficult to differentiate how much effects corticosteroids actually have on DIIHA.
    If drug-independent autoantibodies are involved and stopping the offending agents results in no response then intravenous immunoglobulins and immunosuppressants such as rituximab, azathioprine, cyclophosphamide, cyclosporine, danazol, and mycophenolate can be used. Improvement is typically seen within a few weeks of cessation of the offending drug.


    See also


    Drug-induced nonautoimmune hemolytic anemia
    Warm antibody autoimmune hemolytic anemia
    Autoimmune hemolytic anemia


    References




    Further reading


    Chan, Maverick; Silverstein, William K.; Nikonova, Anna; Pavenski, Katerina; Hicks, Lisa K. (April 28, 2020). "Bendamustine-induced immune hemolytic anemia: a case report and systematic review of the literature". Blood Advances. 4 (8). American Society of Hematology: 1756–1759. doi:10.1182/bloodadvances.2020001726. ISSN 2473-9529. PMC 7189296. PMID 32343794.
    Mayer, Beate; Bartolmäs, Thilo; Yürek, Salih; Salama, Abdulgabar (2015). "Variability of Findings in Drug-Induced Immune Haemolytic Anaemia: Experience over 20 Years in a Single Centre". Transfusion Medicine and Hemotherapy. 42 (5). S. Karger AG: 333–339. doi:10.1159/000440673. ISSN 1660-3796. PMC 4678312. PMID 26696803.
    Salama, Abdulgabar (2009). "Drug-induced immune hemolytic anemia". Expert Opinion on Drug Safety. 8 (1). Informa UK Limited: 73–79. doi:10.1517/14740330802577351. ISSN 1474-0338. PMID 19236219. S2CID 263607634. Retrieved November 21, 2023.


    External links

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drug induced autoimmune hemolytic anemia

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Drug-induced immune hemolytic anemia | Hematology, ASH ...

Jan 1, 2009 · Drug-induced immune hemolytic anemia (DIIHA) is rare. The incidence of drug-induced immune thrombocytopenia and neutropenia is quite well documented (10 to 18 and 2 …

Drug-induced hemolytic anemia - UpToDate

This topic discusses common drugs implicated in causing hemolysis, their mechanisms, patient evaluation, and management. Separate topic reviews discuss the general approach to …

Drug-induced autoimmune hemolytic anemia - Wikipedia

Drug-induced autoimmune hemolytic anemia also known as Drug-induced immune hemolytic anemia (DIIHA) is a rare cause of hemolytic anemia. It is difficult to differentiate from other …

Drug-Induced Autoimmune Hemolytic Anemia: Detection of New ...

Nov 15, 2022 · Introduction More than 130 drugs have been suspected to induce autoimmune hemolytic anemia (AIHA), listed in 2014 (Garratty et al. Immunohematology). Several …

Drug-induced immune hemolytic anemia - PubMed

Drug-induced immune hemolytic anemia (DIIHA) is rare, and a specialized laboratory is often required to provide the optimal serological tests to confirm the diagnosis. The most common …

Drug-induced immune hemolytic anemia (Direct Antiglobulin ...

To date, about 100 drugs have been implicated in causing a positive Direct Antiglobulin Test (DAT) and/or hemolytic anemia. The most common drugs associated with this, are penicillin …

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We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a …

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(6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug.

A leap in recognizing drug-induced immune hemolytic anemia

Feb 13, 2024 · Drug-induced immune hemolysis remains a serious and unrecognized diagnosis. Combining data from pharmacovigilance and clinical care, the comprehensive study …

Drug-induced immune hemolytic anemia - MedlinePlus

Feb 2, 2023 · Drug-induced immune hemolytic anemia is a blood disorder that occurs when a medicine triggers the body's defense (immune) system to attack its own red blood cells. This …