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Immune Mediated Haemolytic Anaemia (view source)
Revision as of 10:23, 16 August 2010
, 10:23, 16 August 2010no edit summary
(IMHA)
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'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
{cellpadding="10" cellspacing="0" border="1"
| Also known as:
| IMHA
| Autoimmune haemolytic anaemia (AIHA)
|}
==Description==
Immune-mediated haemolytic anaemia (IMHA) is the result of a [[Type II Hypersensitivity - WikiBlood|type II antibody-mediated immune response]] directed against molecules expressed on the surface of erythrocytes. The clinical presentation of the disease depends on the isotype of antibody produced and the severity of the anaemia.
[[IgM]] antibodies are capable of fixing complement on the surface of red blood cells leading to the assembly of a membrane attack complex. This complex causes the direct lysis of erythrocytes and '''intravascular haemolysis'''. Since IgM antibodies have a high avidity, they are also able to co-ordinate the formation of large numbers of red blood cells into aggregates, a phenomenon known as '''auto-agglutination'''.
Some types of [[IgG]] antibody are able to directly activate the complement cascade but, in most cases, these antibodies are not able to cause intravascular haemolysis of agglutination and they are therefore described as '''incomplete''' antibodies. These antibodies act as opsonins and, through their interaction with Fc receptors expressed by cells of the hepatosplenic monocyte-phagocyte system (MPS), they promote the uptake and destruction of the red blood cells to which they are bound. These types of antibody therefore cause '''extravascular haemolysis'''.
IMHA may occur as a '''primary''' disease with no apparent cause or it may be '''secondary''' to another systemic insult. Possible secondary causes of IMHA include bacterial and parasite infections (including ''[[Babesia canis]]'' in dogs and ''[[Mycoplasma haemofelis]]'' in cats), adverse drug reactions, neoplasia (especially myeloproliferative and lymphoproliferative disease) and live vaccines, although the association between vaccination and immune-mediated disease remains controversial.
The widespread lysis of red blood cells causes disease in the following ways:
*Blood '''oxygen carrying capacity''' is greatly reduced causing exercise intolerance, collapse and tissue hypoxia.
*The release of '''endogenous procoagulant''' molecules from lysed cells increases the risk of thromboembolism in various tissues, particularly the lungs, spleen and liver.
==Signalment==
Primary IMHA occurs with greater frequency in Cocker spaniels, Old English sheepdogs and standard Poodles but any breed of dog may be affected. Middle-aged, entire female animals have been shown to be at increased risk of developing the disease in some studies.
==Diagnosis==
===Clinical Signs===
Affected animals often present acutely with sudden-onset collapse or severe exercise intolerance. On exmaination, the following signs may become evident:
*'''Pallor''' and/or '''[[Icterus|icterus]]''' of the mucous membranes as the release of bilirubin from lysed red blood cells may result in pre-hepatic jaundice in severely affected animals.
*A '''haemic heart murmur''' and a '''hyperdynamic peripheral pulse''' due to the reduction in viscosity of the blood.
*'''Hepatosplenomegaly''' may be apparent in cases of extravascular haemolysis where the activity of the MPS is greatly increased.
*'''Tachypnoea''' frequently occurs as animals attempt to compensate for reduced tissue oxygenation and blood oxygen carrying capacity.
*'''Dyspnoea''' may occur in animals which develop pulmonary thromboemboli or disseminated intravascular coagulation.
===Laboratory Tests===
On presentation, full biochemical and haematological analysis of blood samples are indicated to confirm the diagnosis and to obtain a baseline measurement to assess the efficiacy of future treatment. Several tests are also available that have a higher specificity for the diagnosis of IMHA.
====Haematology====
Affected animals have a reduced [[Packed Cell Volume|packed cell volume]] (PCV) or haematocrit (HCT) and often a reduced haemoglobin concentration. IMHA causes a strongly [[Anaemia - Introduction|regenerative anaemia]] and evidence of macrocytosis (increased MCV) should be apparent after 48-72 hours in dogs. A blood smear is extremely useful in evaluating cases of IMHA as '''spherocytes''' are often visible. These small, dense red blood cells are formed due to partial phagocytosis of red blood cells by the MPS. Polychromasia should also be visible on a blood smear from an animal undergoing regeneration and reticulocytosis can be confirmed using a supravital stain such as new methylene blue.
Reactive thrombocytosis and leucocytosis may be present with any cause of anaemia.
====Biochemistry====
Serum bilirubin concentration will be elevated and this may be usfficiently severe to cause [[Icterus|icterus]]. The serum [[urea]] concentration may also be elevated as the kidneys receive less oxygen than normal causing a pre-renal azotaemia. A similar process of tissue hypoxia may also result in elevations in liver enzymes such as ALT and AST.
====Other Tests====
An '''in-saline agglutination''' test may be used to diagnose cases of IMHA that involve aut-agglutination. A drop of whole blood is mixed with a drop of plain saline on a glass slide and agitated for 30-60 seconds. A positive result is recorded if evident aggregates form but the slide should be evaluated under a microscope as rouleaux formation may result in a similar gross appearance.
A '''Coomb's test''' can be used to diagnose cases of IMHA that are caused by incomplete antibodies. The red blood cells from a patient are mixed with Coomb's antiserum (IgG antiobies directed against IgG) and, in cases where the patient has IMHA with antibodies attached to the surface of the erythrocytes, the antiserum will result in the formation of aggregates of cells. The titre of the test should be evaluated as weakly positive results may occur with other diseases.
===Diagnostic Imaging===
Imaging may be indicated to rule out other potential causes of the signs observed but it is not always necessary to make a diagnosis of IMHA. Hepatosplenomegaly will be the major findings on both radiographs and ultrasound scans.
==Treatment==
Affected animals often present acutely and may require intensive care. The ultimate aim of long-term treatment for IMHA is to control the autoimmune response.
===Stabilisation===
===Immunosuppressive Therapy===
===Adjunctive Therapy===
==Prognosis==
[[Category:Antibody Mediated Autoimmune Diseases]]
[[Category:Antibody Mediated Autoimmune Diseases]]
[[Category:To Do - James]]
[[Category:To Do - James]]
[[Category:Dog]][[Category:Cat]]