ReviewDiagnosis and classification of autoimmune hemolytic anemia
Introduction
Hematology has long fascinated mankind. As early as 400 BC Hippocrates toiled with the humoral theory that attempted to correlate blood components with health and disease. Early studies such as those by Andral in 1843 first described idiopathic anemia described as “without previous blood loss” and “typically associated with darkened urine” [1]. The first association of hemolytic anemia with jaundice specifically being distinguished from hepatic diseases was described by Hayem in 1898. Hayem is credited with the initial description of congenital and acquired hemolytic anemias [1], [2]. A more complete understanding of human hematology led to what is considered to be the first description of autoantibody-mediated autoimmune disease by Donath and Landsteiner in the early 1900s. Further refinements in analytical methods led to a better understanding of the immune system, and based on this in 1951 autoimmune hemolytic anemia (AIHA) was first described as a specific disorder [1].
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Epidemiology
AIHA is now known as a disease in which autoantibodies are produced that target RBC antigens, resulting in the premature destruction with inadequate compensation [3], [4]. This group of diseases is relatively rare, affecting approximately 1–3 in 100,000 annually [5], [6], [7]. AIHA is primarily limited to adults although children with primary immunodeficiency disease or autoimmune lymphoproliferative syndrome (ALPS) are commonly affected [8]. Children often develop a more self-limited disease
Pathophysiology and classification
Classification of AIHA is pathophysiologically based and divides AIHA into warm, mixed or cold-reactive subtypes, Table 1. This thermal-based classification is based on the optimal RBC-autoantibody reactivity temperatures. AIHA can be further classified into primary (idiopathic) or secondary in nature [5], [6], [10], [11], [12]. Further sub-classification of cold AIHA (cAIHA) includes primary and secondary cold agglutinin syndrome (CAS) and paroxysmal cAIHA [10], [11], [12].
While AIHA and cAIHA
Clinical manifestations
Presenting complaints of AIHA are usually referable to the anemia itself, although occasionally jaundice is the primary manifestation. The onset of symptoms is typically slow or insidious over several months, but occasionally a patient may manifest with acute severe life threatening symptoms. In secondary AIHA the symptoms of the underlying or precipitating disease may overshadow the manifestations of AIHA. The physical examination may be normal with splenomegaly being present in approximately
wAIHA
The first and most important criterion for the diagnosis of AIHA is the recognition of hemolysis and anemia. The appearance of jaundice and abnormally dark urine is usually suggestive of hemolysis but is only present in approximately 60% of patients. When diagnosing AIHA it is important to first rule out other causes of hemolysis such as microagiopathy, hereditary conditions (i.e. spherocytosis or G6PD) or sickle cell anemia. The predominant laboratory features are a positive direct
wAIHA
Unfortunately there are few prospective clinical trials that have established treatment standards for patients with AIHA. The majority of the data is from retrospective case studies and recommendations are often experience-based. There is no accepted consensus on the definition of complete (CR) or partial remission (PR) or refractoriness. Many of these patients have an insidious course and transfusions are not required. However occasionally when there is rapid hemolysis and/or the patient has
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