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Also known as: '''''ITP — Idiopathic Thrombocytopaenic Purpura — [[Evan's syndrome|Evan’s Syndrome]]

Also known as: '''''ITP — Idiopathic Thrombocytopaenic Purpura — [[Evan's syndrome|Evan’s Syndrome]]

==Introduction==

==Introduction==

Immune-mediated thrombocytopaenia (ITP) occurs due to an autoimmune response directed against circulating platelets or megakaryocytes in the bone marrow.  The destruction of cells is mediated by antibodies, making ITP a form of '''[[Type II Hypersensitivity|type II hypersensitivity]]'''.  The antibodies bind to cells and act as a foundation for the assembly of serum complement components or as opsonins, promoting the uptake and destruction of platelets by cells of the monocyte-phagocyte system (MPS). The destruction of platelets usually results in severe [[Platelet Abnormalities|thrombocytopaenia]] and, if the blood level of platelets fall below approximately 50x10^9/l, the affected animal is at risk of mucosal haemorrhages.   

Immune-mediated thrombocytopaenia (ITP) occurs due to an autoimmune response directed against circulating platelets or megakaryocytes in the bone marrow.  The destruction of cells is mediated by antibodies, making ITP a form of '''[[Type II Hypersensitivity|type II hypersensitivity]]'''.  The antibodies bind to surface recptors on the platelets and act as a foundation for the assembly of serum complement components or as opsonins, promoting the uptake and destruction of platelets by cells of the monocyte-phagocyte system (MPS). The destruction of platelets usually results in severe [[Platelet Abnormalities|thrombocytopaenia]] and, if the blood level of platelets fall below approximately 50x10^9/l, the affected animal is at risk of mucosal haemorrhages.   

ITP may be '''primary''' (with no apparent underlying cause) or '''secondary''' to another disease process, to an infection or as a reaction to some drugs. ITP that occurs concurrently with [[Immune Mediated Haemolytic Anaemia|immune-mediated haemolytic anaemia]] (IMHA) is known as '''Evan’s syndrome'''.

ITP may be '''primary''' (with no apparent underlying cause) or '''secondary''' to another disease process; infections, neoplasia, other automimmune diseases, transfusion reactions and drug reactions (particularly antibiotics) are underlying conditions that can cause a secondary ITP . ITP that occurs concurrently with [[Immune Mediated Haemolytic Anaemia|immune-mediated haemolytic anaemia]] (IMHA) is known as '''Evan’s syndrome'''.

==Signalment==

==Signalment==

===Laboratory Tests===

===Laboratory Tests===

Haematological analysis of a blood sample will show '''thrombocytopaenia''', often with extremely low platelet counts (e.g. 1-5x10^9/l). There may be a reactive [[Neutrophilia|neutrophilia]] and other features of a stress leucogram. Examination of a blood smear may show evidence of '''microthrombocytes''' (small platelets that have been partially phagocytosed by cells of the MPS, similar to spherocytes in IMHA) or immature '''macrothrombocytes''' (a sign of bone marrow platelet regeneration). The patient may be anaemic in cases of Evan’s syndrome or if significant haemorrhage has occurred.

Haematological analysis of a blood sample will show '''thrombocytopaenia''', often with extremely low platelet counts (e.g. 1-5x10^9/l). There may be a reactive [[Neutrophilia|neutrophilia]] and other features of a [[Stress Leucogram|stress leucogram]]. Examination of a blood smear may show evidence of '''microthrombocytes''' (small platelets that have been partially phagocytosed by cells of the MPS, similar to spherocytes in IMHA) or immature '''macrothrombocytes''' (a sign of bone marrow platelet regeneration). The patient may be anaemic in cases of Evan’s syndrome or if significant haemorrhage has occurred.

===Other Tests===

===Other Tests===

Definitive diagnosis relies on the detection of serum anti-platelet antibodies but this test is not widely available.

Definitive diagnosis relies on the detection of serum anti-platelet antibodies but this test is not widely available.

Other tests may also be used to exclude potential infectious causes of thrombocytopaenia such as ''[[Ehrlichia platys]]'' and ''Anaplasma phagocytophilum''.   

Other tests may also be used to exclude potential infectious causes of thrombocytopaenia such as ''[[Ehrlichia platys]]'' and ''[[Anaplasma phagocytophilum]]''.   

Faecal occult blood tests represent an unreliable way of detecting gastro-intestinal haemorrhage in cases of mild melaena. The animal must be deprived of meat, bismuth subsalicylate and ferrous sulphate for 3 days before the faecal samples are taken for analysis.

Faecal occult blood tests represent an unreliable way of detecting gastro-intestinal haemorrhage in cases of mild melaena. The animal must be deprived of meat, bismuth subsalicylate and ferrous sulphate for 3 days before the faecal samples are taken for analysis.

Bone Marrow aspirates are not diagnostic

Bone Marrow aspirates are not diagnostic for this condition.

===Diagnostic Imaging===

===Diagnostic Imaging===

The ultimate goal of the therapeutic regime is to control the autoimmune response to prevent further destruction of platelets. The bone marrow stem cells will then be able to replace the platelets that have been lost in the disease. A variety of drugs have been used in the treatment of ITP but those in widespread use include:

The ultimate goal of the therapeutic regime is to control the autoimmune response to prevent further destruction of platelets. The bone marrow stem cells will then be able to replace the platelets that have been lost in the disease. A variety of drugs have been used in the treatment of ITP but those in widespread use include:

*'''Corticosteroids''' including prednisolone and dexamethasone act to suppress cell- and antibody-mediated responses. These drugs act quickly, are frequently effective and are widely available, making them the most commonly used drugs in the management of ITP.

*'''Corticosteroids''' including prednisolone and dexamethasone act to suppress cell- and antibody-mediated responses. These drugs act quickly, are frequently effective and are widely available, making them the most commonly used drugs in the management of ITP.

*Adjunctive immunosuppressive therapy may be provided with '''ciclosporin''', '''azathioprine''' or '''cyclophosphamide'''.

*Adjunctive immunosuppressive therapy may be provided with '''ciclosporin''', '''azathioprine''' or '''cyclophosphamide'''. Ketaconazole and Cyclosporin can be used synergistically to reduce the dose of Cyclosporin/Ciclosporin used because of Ketaconazole's ability to inhibit the enzyme cytochrome P450.

*A recent prospective study indicated that '''human immunoglobulin''' may produce a significantly better outcome in cases of ITP. This product is thought to act by occupying sites (Fc receptors) on cells of the MPS that are usually used to recognise opsonised platelets and mediate phagocytosis.  Although it seems to be highly effective, this product is extremely expensive.

*A recent prospective study indicated that '''human immunoglobulin''' may produce a significantly better outcome in cases of ITP. This product is thought to act by occupying sites (Fc receptors) on cells of the MPS that are usually used to recognise opsonised platelets and mediate phagocytosis.  Although it seems to be highly effective, this product is extremely expensive and is perhaps best indicated in actively bleeding or refractory cases.

*'''Vincristine''' is occasionally used in cases of severe thrombocytopaenia as it is thought to cause the release of platelets from the bone marrow.  The immature platelets released however are not completely functional. It also reduces macrophage function by inhibiting the assembly of microtubules necessary for phagocytosis.

*'''Vincristine''' is occasionally used in cases of severe thrombocytopaenia as it is thought to cause the release of platelets from the bone marrow.  The immature platelets released however are not completely functional. It also reduces macrophage function by inhibiting the assembly of microtubules necessary for phagocytosis.

*'''Splenectomy''' may be performed in cases refractory to medical management to remove the cells responsible for the phagocytosis of platelets.

*'''Splenectomy''' may be performed in cases refractory to medical management to remove the cells responsible for the phagocytosis of platelets. Whilst this can be considered in cases that have frequent relapses, the hepatic mononuclear phagocytic system can also destroy platelets so splenectomy does not always ameliorate symptoms.

==Prognosis==

==Prognosis==

Similarly to IMHA, mortality is most likely in the initial stages of the disease and the mortality rate is approximately 30% in this period. Beyond this, the majority of animals recover well although they may require immunosuppressive treatment for several months to completely control the disease.

Similarly to IMHA, mortality is most likely in the initial stages of the disease and the mortality rate is approximately 30% in this period. Beyond this, the majority of animals recover well although they usually require tapered immunosuppressive treatment for roughly six months to completely control the disease. Initial responses to treatment are relatively quick, so if no increase in platelet number is seen within 1 week of initiating treatment, investigate further for an underlying cause which requires treatment.

==References==

==References==

Ettinger, S.J, Feldman, E.C. (2005) '''Textbook of Veterinary Internal Medicine''' (6th edition, volume 2) Elsevier Saunders Company

Ettinger, S.J, Feldman, E.C. (2005) '''Textbook of Veterinary Internal Medicine''' (6th edition, volume 2) Elsevier Saunders Company

[[Category:Antibody Mediated Autoimmune Diseases]]

[[Category:Antibody Mediated Autoimmune Diseases]]

[[Category:Dog]][[Category:Cat]][[Category:Expert Review]]

[[Category:Immunological Diseases - Dog]][[Category:Lymphoreticular and Haematopoietic Diseases - Dog]][[Category:Immunological Diseases - Cat]][[Category:Lymphoreticular and Haematopoietic Diseases - Cat]][[Category:Expert Review - Small Animal]]