Warm antibody autoimmune hemolytic anemia

Other names: WAIHA

Warm antibody autoimmune hemolytic anemia (WAIHA) is the most common form of autoimmune haemolytic anemia.[1] 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.[citation needed]

## Contents

* 1 Signs and symptoms
* 2 Causes
* 2.1 Medications
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Clinical findings
* 5 Treatment
* 6 See also
* 7 References
* 8 External links

## Signs and symptoms[edit | edit source]

Skin pallor, icterus and nailbed pallor

The clinical presentation of this condition is consistent with the following:[2]

* Headache
* Abnormal urinary colour
* Congestive heart failure
* Jaundice
* Fatigue

## Causes[edit | edit source]

AIHA may be:

* Idiopathic, that is, without any known cause[3]
* Secondary to another disease, such as an antecedent upper respiratory tract infection, systemic lupus erythematosus or a malignancy, such as chronic lymphocytic leukemia (CLL)[3]

### Medications[edit | edit source]

* Several medications have been associated with the development of warm AIHA. These medications include quinidine, nonsteroidal anti-inflammatory drugs (NSAIDs), alpha methyldopa, and antibiotics such as penicillins, cephalosporins (such as ceftriaxone and cefotetan), and ciprofloxacin.[citation needed]

## Pathophysiology[edit | edit source]

The most common antibody isotype involved in warm antibody AIHA is IgG, though sometimes IgA is found. The IgG antibodies attach to a red blood cell, leaving their FC 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 FC region is recognized and grabbed onto by FC receptors found on monocytes and macrophages in the spleen. 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 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 often seen in these patients.[citation needed]

There are two models for this: the hapten model and the autoantibody model. The hapten model proposes that certain drugs, especially penicillin 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.[citation needed] It is possible for it to occur in an immunocompromised patient.[4]

## Diagnosis[edit | edit source]

Diagnosis is made by a positive direct Coombs test, other lab tests, and clinical examination and history. The direct Coombs test looks for antibodies attached to the surface of red blood cells.[citation needed]

### Clinical findings[edit | edit source]

Laboratory findings include severe anemia, normal MCV (mean corpuscular volume) , and hyperbilirubinemia (from increased red cell destruction) that can be of the conjugated or unconjugated type.[citation needed]

## Treatment[edit | edit source]

Corticosteroids and immunoglobulins are two commonly used treatments for warm antibody AIHA. Initial medical treatment consists of prednisone. If ineffective, splenectomy should be considered.[citation needed]

If refractory to both these therapies, other options include rituximab,[5][6] danazol, cyclosphosphamide, azathioprine, or ciclosporin. 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.[citation needed]

## See also[edit | edit source]

* List of circulatory system conditions

## References[edit | edit source]

1. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, Mo: Elsevier Saunders. p. 637\. ISBN 0-7216-0187-1.
2. ↑ "Warm antibody hemolytic anemia | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Archived from the original on 1 February 2022. Retrieved 11 February 2022.
3. ↑ 3.0 3.1 AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA) Archived 2009-10-07 at the Wayback Machine By J.L. Jenkins. The Regional Cancer Center. 2001
4. ↑ Nowak-Wegrzyn A, King KE, Shirey RS, Chen AR, McDonough C, Lederman HM (May 2001). "Fatal warm autoimmune hemolytic anemia resulting from IgM autoagglutinins in an infant with severe combined immunodeficiency". J. Pediatr. Hematol. Oncol. 23 (4): 250–2. doi:10.1097/00043426-200105000-00015. PMID 11846306.
5. ↑ Morselli M, Luppi M, Potenza L, et al. (May 2002). "Mixed warm and cold autoimmune hemolytic anemia: complete recovery after 2 courses of rituximab treatment". Blood. 99 (9): 3478–9. doi:10.1182/blood-2002-01-0018. PMID 12001903.
6. ↑ Bussone G, Ribeiro E, Dechartres A, et al. (December 2008). "Efficacy and safety of rituximab in adults' warm antibody autoimmune haemolytic anemia: Retrospective analysis of 27 cases". Am. J. Hematol. 84 (3): 153–7. doi:10.1002/ajh.21341. PMID 19123460. S2CID 205292170.

## External links[edit | edit source]

* Case report of warm-antibody autoimmune hemolytic anemia with typical laboratory findings. Clinical Cases and Images.

Classification|

* ICD-10: D59.1
* ICD-9-CM: 283.0
* DiseasesDB: 29723

|

* v
* t
* e

Diseases of red blood cells

| Polycythemia|

* Polycythemia vera

|

| Anemia|

| Nutritional|

* Micro-: Iron-deficiency anemia
* Plummer–Vinson syndrome

* Macro-: Megaloblastic anemia
* Pernicious anemia

|

Hemolytic
(mostly normo-)|

| Hereditary|

* enzymopathy: Glucose-6-phosphate dehydrogenase deficiency
* glycolysis
* pyruvate kinase deficiency
* triosephosphate isomerase deficiency
* hexokinase deficiency

* hemoglobinopathy: Thalassemia
* alpha
* beta
* delta
* Sickle cell disease/trait
* Hereditary persistence of fetal hemoglobin

* membrane: Hereditary spherocytosis
* Minkowski–Chauffard syndrome
* Hereditary elliptocytosis
* Southeast Asian ovalocytosis
* Hereditary stomatocytosis

|

Acquired|

| AIHA|

* Warm antibody autoimmune hemolytic anemia
* Cold agglutinin disease
* Donath–Landsteiner hemolytic anemia
* Paroxysmal cold hemoglobinuria
* Mixed autoimmune hemolytic anemia

|

* membrane
* paroxysmal nocturnal hemoglobinuria

* Microangiopathic hemolytic anemia
* Thrombotic microangiopathy
* Hemolytic–uremic syndrome

* Drug-induced autoimmune
* Drug-induced nonautoimmune

* Hemolytic disease of the newborn

Aplastic
(mostly normo-)|

* Hereditary: Fanconi anemia
* Diamond–Blackfan anemia

* Acquired: Pure red cell aplasia
* Sideroblastic anemia
* Myelophthisic

Blood tests|

* Mean corpuscular volume
* normocytic
* microcytic
* macrocytic
* Mean corpuscular hemoglobin concentration
* normochromic
* hypochromic

Other|

* Methemoglobinemia
* Sulfhemoglobinemia
* Reticulocytopenia

* v
* t
* e

Human spleen

Structure|

* Hilum
* Trabeculae

Red pulp|

* Cords of Billroth
* Marginal zone

White pulp|

* Periarteriolar lymphoid sheaths
* Germinal center

Blood flow|

* Trabecular arteries
* Trabecular veins

Pain|

* Splenomegaly
* Splenic abscess
* Splenic infarction
* Spleen rupture
* Splenic injury

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