Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of

autoimmune haemolytic anemia Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of ...

. About half of the cases are of unknown cause, with the other half attributable to a predisposing condition or medications being taken. Contrary to cold autoimmune hemolytic anemia (e.g., cold agglutinin disease and paroxysmal cold hemoglobinuria) which happens in cold temperature (28–31 °C), WAIHA happens at body temperature.

Causes

AIHA may be: * Idiopathic, that is, without any known causeAUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)
By J.L. Jenkins. The Regional Cancer Center. 2001 * Secondary to another disease, such as an antecedent upper respiratory tract infection,

systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...

or a malignancy, such as

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever ...

(CLL)

Medications

* Several medications have been associated with the development of warm AIHA. These medications include

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration o ...

s (NSAIDs), alpha methyldopa, and

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

s such as

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from '' Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum usin ...

cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...

s (such as

ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and join ...

and

cefotetan Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional an ...

), and

ciprofloxacin Ciprofloxacin is a fluoroquinolone antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain types of infectious diarrhea, respiratory tract infections, skin i ...

Pathophysiology

The most common

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...

isotype involved in warm antibody AIHA is

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG an ...

, though sometimes

IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a g ...

is found. The IgG antibodies attach to a red blood cell, leaving their F_C portion exposed with maximal reactivity at 37 °C (versus cold antibody induced hemolytic anemia whose antibodies only bind red blood cells at low body temperatures, typically 28-31 °C). The F_C region is recognized and grabbed onto by F_C receptors found on monocytes and macrophages in the

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

. These cells will pick off portions of the red cell membrane, almost as if they are taking a bite. The loss of membrane causes the red blood cells to become spherocytes. Spherocytes are not as flexible as normal RBCs and will be singled-out for destruction in the

red pulp The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorgan ...

of the spleen as well as other portions of the reticuloendothelial system. The red blood cells trapped in the spleen cause the spleen to enlarge, leading to the

splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...

often seen in these patients. There are two models for this: the hapten model and the autoantibody model. The hapten model proposes that certain drugs, especially

and cephalosporins, will bind to certain proteins on the red cell membrane and act as haptens (small molecules that can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself). Antibodies are created against the protein-drug complex, leading to the destructive sequence described above. The autoantibody model proposes that, through a mechanism not yet understood, certain drugs will cause antibodies to be made against red blood cells which again leads to the same destructive sequence. It is possible for it to occur in an immunocompromised patient.

Diagnosis

Diagnosis is made by a positive direct

Coombs test A Coombs test, also known as antiglobulin test (AGT), is either of two blood tests used in immunohematology. They are the direct and indirect Coombs tests. The direct Coombs test detects antibodies that are stuck to the surface of the red blood c ...

, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.

Clinical findings

Laboratory findings include severe

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

, normal MCV (mean corpuscular volume), and

hyperbilirubinemia Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

(from increased red cell destruction) that can be of the conjugated or unconjugated type.

Treatment

Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial medical treatment consists of prednisone. If ineffective,

splenectomy A splenectomy is the surgical procedure that partially or completely removes the spleen. The spleen is an important organ in regard to immunological function due to its ability to efficiently destroy encapsulated bacteria. Therefore, removal of ...

should be considered. If refractory to both these therapies, other options include rituximab, danazol,

cyclosphosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast can ...

azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...

, or

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease ...

. High-dose intravenous immune globulin may be effective in controlling hemolysis, but the benefit is short lived (1–4 weeks), and the therapy is very expensive.

References

External links

* Case report o
warm-antibody autoimmune hemolytic anemia
with typical laboratory findings. Clinical Cases and Images * The wAIHA Warriors is a 501(c)3 support and advocacy group for caregivers and patients of warm autoimmune hemolytic anemia. www.waihawarriors.org {{DEFAULTSORT:Warm Autoimmune Hemolytic Anemia Autoimmune diseases Acquired hemolytic anemia Hematopathology Rare diseases