Difference between revisions of "Platelet Abnormalities"

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[[Image:LH_Platelet_Histology.jpg|right|thumb|175px|<center><p>'''Platelets'''</p><sup>©RVC 2008</sup></center>]]
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{{unfinished}}
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==Introduction==
 
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[[Platelet|Platelets]] (or thrombocytes) are responsible for primary haemostasis by the formation of a temporary platelet plug that initially seals any breach to a blood vessel wall.  These breaches are then sealed more completely by the formation of a fibrin clot induced by the coagulation factor cascade. 
 
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===Terminology===
 
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*'''Thrombocytopaenia''' refers to low absolute numbers of platelets. Infections, neoplasia and [[Immune Mediated Thrombocytopaenia|immune-mediated thrombocytopaenia]] (ITP) are common causes of thrombocytopaenia, which is frequently a secondary disease. 
 
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*'''Thrombocytopathia''' refers to platelets that are unable to function adequately.
 
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*'''Thrombocytosis''' refers to an increase in the blood platelet concentration above the normal level.
 
  
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Thrombocytopaenia and thrombocytopathia lead to disorders of primary haemostasis but, in general, this is less serious than the disorders of secondary haemostasis caused by deficiencies in the [[Coagulation Factor Deficiency|coagulation factors]].
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==Description==
 +
[[Platelet|Platelets]] (or thrombocytes) are responsible for primary haemostasis, the formation of a temporary platelet plug that initially seals any breach to a blood vessel wall.  Bleeding disorders may occur if platelets are deficient ('''thrombocytopaenia''') or if the platelets are unable to function adequately ('''thrombocytopathia''').  [[Immune Mediated Thrombocytopaenia|Immune-mediated thrombocytopaenia]] (ITP) is one common cause of thrombocytopaenia and this may be a primary or secondary disease.  '''Thrombocytosis''' refers to an increase in the blood platelet concentration above the normal level.
 +
 
 +
Thrombocytopaenia and thrombocytopathia lead to disorders of primary haemostasis but, in general, this is less serious than the disorders of secondary haemostasis caused by deficiencies in the [[Coagulation Factor Deficiency|clotting factors]].
  
 
==Thrombocytopaenia==
 
==Thrombocytopaenia==
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Thrombocytopaenia is a common haematological abnormality as platelet numbers are subject to fluctuation in a number of diseases. Care should be taken, however to ensure that this finding is not caused by an artefact of sampling where platelet clumps have formed.  The normal blood platelet concentration of the dog is 175-500x10^9; a tendency to bleed following an insult such as venepuncture can be observed if levels fall below 50x10^9 and spontaneous haemorrhage is observed when levels fall below 30x10^9. Acute thrombocytopenia is more likley to give rise to clinical signs than more chronically developed low platelet numbers.
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Thrombocytopaenia is the most common haematological abnormality as platelet numbers are subject to fluctation in a large number of different diseases however care should be taken to ensure that this finding is not caused by an artefact of sampling.  The normal blood platelet concentration of the dog is 175-500x10^9 but clinical disease is not usually observed until this level falls below 50x10^9 and spontaneous haemorrhage is observed only when the level falls below 20x10^9. Reductions in the number of platelets may be caused by failure to produce adequate numbers in the bone marrow in the process of megakaryopoiesis, increased destruction of existing platelets or sequestration of platelets outside of the circulation.   
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*Diseases that cause '''[[Bone Marrow - Anatomy & Physiology|bone marrow]] suppression'''
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Reductions in platelet numbers may be caused by a failure to produce adequate amounts in the bone marrow during [[Thrombopoiesis|megakaryopoiesis]], or an increased destruction of existing platelets or sequestration of platelets outside of the circulation.   
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**'''Aplastic anaemia''' caused by ingestion of bracken, administration of oestrogens or of [[Chloramphenicol|chloramphenicol]] or [[Sulphonamides|sulphonamide]] antibiotics.  Prolonged use of phenylbutazone or salicylate may cause the same disease.
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**'''Infectious diseases''' that reduce stem cell function, including [[Distemper|canine distemper virus]], [[Canine Parvovirus|canine parvovirus]] and [[Feline Panleucopaenia|feline panleucopaenia virus]].
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===Causes of bone marrow suppression===
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**'''Myelophthisis''', the displacement of the normal cell lines of the bone marrow by another cell or tissue type may also reduce the function of the megakaryocytes. Possible diseases include '''myelofibrosis''' and '''immunoproliferative''' or '''myeloproliferative''' neoplastic disease.
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*'''Aplastic anaemia''' which can be caused by the ingestion of bracken or administration of oestrogens, [[Chloramphenicol|chloramphenicol]] or [[Sulphonamides|sulphonamide]] antibiotics.  Prolonged use of [[NSAIDs#Phenylbutazone|phenylbutazone]] or salicylates may cause the same disease.
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**'''Radiotherapy''' or myelosuppressive '''chemotherapy''' may cause reversible bone marrow suppression.
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*'''Infectious diseases''' that reduce stem cell function include [[Distemper|canine distemper]], [[Canine Parvovirus|canine parvovirus]] and [[Feline Panleucopaenia|feline panleucopaenia virus]].
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*Diseases that cause '''increased destruction of platelets'''
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*'''Myelophthisis''' is the displacement of the normal cell lines of the bone marrow by another cell or tissue type which may also reduce the function of the megakaryocytes. Diseases in this category include '''myelofibrosis''' and '''immunoproliferative''' or '''myeloproliferative''' neoplastic disease.
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**'''[[Immune Mediated Thrombocytopaenia|Immune-mediated thrombocytopaenia]]''' is a common autoimmune disease that leads to the destruction of platelets by cell of the monocyte phagocyte system (MPS).
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*'''Radiotherapy''' or myelosuppressive '''chemotherapy''' may cause reversible bone marrow suppression.
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**'''Infectious diseases''' that cause destruction of platelets include [[Bovine Viral Diarrhoea Virus|bovine viral diarrhoea]], [[Classical Swine Fever|classical swine fever]] and [[Infectious Canine Hepatitis|infectious canine hepatitis]].  The parasites ''[[Ehrlichia platys]]'', ''[[Ehrlichia phagocytophila|Anaplasma phagocytophilum]]'' and ''[[Ehrlichia canis]]'' may also cause infectious thrombocytopaenia.  Any severe bacterial infection, including those caused by [[:Category:Staphylococcus species|''Staphylococci'']] and the Gram negative bacteria that produce endotoxin (e.g. [[:Category:Pseudomonas and Burkholderia species|''Pseudomonas spp.'']] or [[Salmonella|''Salmonella spp.'']]) may also result in the destruction of platelets.
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*Diseases that cause '''sequestration of platelets''' usually involve some enlargement of the spleen as this is the major organ where platelets are stored outside of the circulation.  Examples include:
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===Causes of increased platelet destruction===
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**[[Haemangiosarcoma]] of the spleen and liver
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*'''Infectious diseases''' that cause destruction of platelets include [[Bovine Viral Diarrhoea Virus|bovine viral diarrhoea (BVD)]], [[Classical Swine Fever|classical swine fever]] and [[Infectious Canine Hepatitis|infectious canine hepatitis]].  The parasites [[Ehrlichia platys|''Anaplasma platys'']], [[Ehrlichia phagocytophila|''Anaplasma phagocytophilum'']] and ''[[Ehrlichia canis]]'' may also cause infectious thrombocytopaenia.  Any severe bacterial infection, including those caused by [[:Category:Staphylococcus species|''Staphylococci'']] and the Gram negative bacteria that produce endotoxins (e.g. [[:Category:Pseudomonas and Burkholderia species|''Pseudomonas sp.'']] or [[Salmonella|''Salmonella sp.'']]) may also result in the destruction of platelets.
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**Splenic enlargement under general anaesthesia maintained with agents such as [[Barbiturates|barbiturates]] and [[Phenothiazines|phenothiazines]]
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*'''[[Immune Mediated Thrombocytopaenia|Immune-mediated thrombocytopaenia]]''' is an autoimmune disease that leads to the production of antibodies against platelets and their subsequent destruction by cells of the [[Monocytes|monocyte]] phagocyte system (MPS). Platelet numbers can be very low in animals with this condition, but infection and neoplasias are more common causes of thrombocytopaenia.
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*'''Artefactual'''  or spurious thrombocytopaenia
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**'''Cavalier King Charles spaniels''' have a relatively small number of giant platelets (macrothrombocytes) but they do not suffer from bleeding disorders as they maintain a similar total platelet mass as do dogs of other breeds.
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===Causes of platelet sequestration===
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**If venepuncture is traumatic, '''platelet clumps''' may form and these will not be counted by automated machines.  The presence of clumps can be investigated by making a blood smear and examining the feathered edge for large agglomerations of platelets.
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Diseases that cause '''sequestration of platelets''' usually involve some enlargement of the spleen, as this is the major organ where platelets are stored outside of the circulation.  A common example would be [[Haemangiosarcoma|haemangiosarcoma]] of the spleen and liver. Splenic enlargement under general anaesthesia maintained with agents such as [[Barbiturates|barbiturates]] and [[Phenothiazines|phenothiazines]] can also lead to sequestration of platelets.
 
−
 
 
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===Artefactual or spurious thrombocytopaenia===
 
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*'''Cavalier King Charles spaniels''' have a genetic abnormality which produces a small number of giant platelets (macrothrombocytes) in the circulation with a corresponding reduction in free platelets; they do not suffer from bleeding disorders as they maintain a similar total platelet mass as do dogs of other breeds. Automated blood counts will include the macrothrombocytes in the white or red cell count and the apparent thrombocytopenia will be exaggerated.  
 
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*'''Greyhounds''' and other sight hounds frequently have platelet counts at the lowest end of the reference range (as well as increased haematocrit, mild neutropaenia and reduced T4 levels) but this is a normal finding for this breed.
 
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*If venepuncture is traumatic (using small viens with excessive suction or patient agitation) '''platelet clumps''' may form and these will not be counted by automated machines.  The presence of clumps can be investigated by making a blood smear and examining the feathered edge for large agglomerations of platelets. Time, temperature and contact with glass can also cause clumping of platelets once the sample has been taken.
 
  
 
==Thrombocytopathia==
 
==Thrombocytopathia==
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Defects in platelet function may be congenital or acquired in association with a number of diseases.  Congenital thrombocytopathias are rare inherited diseases which are characterised by defects in platelet adhesiveness, aggregation or factor release.  The defects are usually associated with particular breeds, such as '''Chediak-Higashi syndrome''' in blue smoke Persian cats.
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Defects in platelet function may be congenital defects or they may be acquired with a number of diseases.  Congenital thrombocytopathias are rare inherited diseases which are characterised by defects in platelet adhesiveness, aggregation and factor release.  The defects are usually associated with particular breeds, such as Chediak-Higashi syndrome in blue smoke Persian cats.
  
 
Causes of acquired thrombocytopathia include:
 
Causes of acquired thrombocytopathia include:
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*Infection with ''[[Angiostrongylus vasorum]]'', the canine lungworm, which also causes a consumptive coagulopathy.
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*'''Hypergammaglobulinaemia''' as occurs with multiple myeloma and some forms of (B-cell) lymphoma may affect platelet function.
 
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*Administration of large volumes of some '''[[Colloids|colloid solutions]]'''.
 
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*Administration of certain '''pharmaceutical products''', including [[NSAIDs|non-steroidal anti-inflammatory drugs]] and [[Cephalosporins|cephalosporins]].
 
  
 
==Thrombocytosis==
 
==Thrombocytosis==
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Increased platelet number above normal levels may occur due to physiological or pathological processes.   
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Increases in platelets above the normal level may occur due to '''physiological''' or '''pathological''' processes.   
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*Physiological
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Physiological causes include:
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**'''Splenic contraction''' pushes sequestered platelets into the circulation.  This phenomenon is especially marked in horses which have a muscular splenic capsule.   
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*'''Splenic contraction''' which pushes sequestered platelets into the circulation.  This phenomenon is especially marked in '''horses''' which have a muscular splenic capsule.   
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**'''Splenectomy''' prevents the sequestration of platelets in the spleen, resulting in constantly increased levels of platelets.
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*'''Splenectomy''' prevents the sequestration of platelets in the spleen, resulting in consistently increased levels of platelets.
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**As part of a response to '''anaemia''', a '''reactive thrombocytosis''' is often documented and this may precede signs of regeneration.
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*As part of a response to [[Regenerative and Non-Regenerative Anaemias|anaemia]] a '''reactive thrombocytosis''' is often documented and this may precede signs of regeneration.
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*Pathological
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**'''Essential thrombocythaemia'''
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Pathological
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**Megakaryocytic leukaemia
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*'''Essential thrombocythaemia''' is a rare myeloproliferative disease that results in the excessive production of platelets which function abnormally.  Affected animals suffer from bouts of spontaneous haemorrhage.
 
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==Clinical Significance==
 
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Other than essential thrombocythaemia, thrombocytosis has no clinical importance except as an indicator of another disease process.  Thrombocytopaenia and thrombocytopathia both result in reductions in the effectiveness of primary haemostasis, producing bleeding disorders.  Since bleeding points are usually sealed by a fibrin clot, disorders of primary haemostasis tend to be less severe than those caused by deficiencies of the coagulation factors.  Common signs of a disorder of primary haemostasis include:
 
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*Petechial or ecchymotic [[Haemorrhage|haemorrhages]] on the skin or mucous membranes.
 
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*[[Haemorrhage|Haemorrhages]] from the mucous membranes, producing haematuria, haematochezia, haematemesis, haemoptysis and melaena.
 
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*[[Regenerative and Non-Regenerative Anaemias|Anaemia]] with a reactive [[Neutrophilia|neutrophilia]] and [[Monocytosis|monocytosis]] if the haemorrhage is severe.
 
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Severe platelet deficiencies may be managed with transfusions of whole blood or, in the USA, with transfusions of platelet cryoprecipitate - this helps to control the anaemia which occurs as a consequence of haemorrhage and which is the life threatening sympton that required correction (rather than the thrombocytopenia).  With both techniques however, it is likely that the transfused platelets have only a short half life in the recipient. 
 
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The use of Vincristine (a drug also used in chemotherapy for neoplasia) has been advocated in cases of thrombocytopaenia as it increases the rate of fragmentation of megakaryocytes and decreases the descruction of platelets by macrophages. A single intravenous dose is usually given.
 
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{{Learning
 
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|literature search = [http://www.cabdirect.org/search.html?q=title%3A%28thrombocytopenia%29+OR+title%3A%28thrombocytopaenia%29&fq=sc%3A%22ve%22 Thrombocytopaenia publications]
 
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[http://www.cabdirect.org/search.html?q=title%3A%28thrombocytopathia%29+ Thrombocytopathia publications]
 
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[http://www.cabdirect.org/search.html?q=title%3A%28thrombocytosis%29&fq=sc%3A%22ve%22 Thrombocytosis publications]
 
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|flashcards = [[Small Animal Emergency and Critical Care Medicine Q&A 21]]
 
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}}
 
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[[Category:Haemorrhagic Diseases]]
 
[[Category:Haemorrhagic Diseases]]
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[[Category:Haematology Changes]]
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[[Category:To Do - James]][[Category:Blood Cell Changes]]
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[[Category:Lymphoreticular and Haematopoietic Diseases - Dog]]
 
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[[Category:Cardiology Section]]
 

Revision as of 17:07, 18 August 2010


 This article is still under construction.


Description

Platelets (or thrombocytes) are responsible for primary haemostasis, the formation of a temporary platelet plug that initially seals any breach to a blood vessel wall. Bleeding disorders may occur if platelets are deficient (thrombocytopaenia) or if the platelets are unable to function adequately (thrombocytopathia). Immune-mediated thrombocytopaenia (ITP) is one common cause of thrombocytopaenia and this may be a primary or secondary disease. Thrombocytosis refers to an increase in the blood platelet concentration above the normal level.

Thrombocytopaenia and thrombocytopathia lead to disorders of primary haemostasis but, in general, this is less serious than the disorders of secondary haemostasis caused by deficiencies in the clotting factors.

Thrombocytopaenia

Thrombocytopaenia is the most common haematological abnormality as platelet numbers are subject to fluctation in a large number of different diseases however care should be taken to ensure that this finding is not caused by an artefact of sampling. The normal blood platelet concentration of the dog is 175-500x10^9 but clinical disease is not usually observed until this level falls below 50x10^9 and spontaneous haemorrhage is observed only when the level falls below 20x10^9. Reductions in the number of platelets may be caused by failure to produce adequate numbers in the bone marrow in the process of megakaryopoiesis, increased destruction of existing platelets or sequestration of platelets outside of the circulation.

  • Diseases that cause bone marrow suppression
    • Aplastic anaemia caused by ingestion of bracken, administration of oestrogens or of chloramphenicol or sulphonamide antibiotics. Prolonged use of phenylbutazone or salicylate may cause the same disease.
    • Infectious diseases that reduce stem cell function, including canine distemper virus, canine parvovirus and feline panleucopaenia virus.
    • Myelophthisis, the displacement of the normal cell lines of the bone marrow by another cell or tissue type may also reduce the function of the megakaryocytes. Possible diseases include myelofibrosis and immunoproliferative or myeloproliferative neoplastic disease.
    • Radiotherapy or myelosuppressive chemotherapy may cause reversible bone marrow suppression.
  • Diseases that cause increased destruction of platelets
  • Diseases that cause sequestration of platelets usually involve some enlargement of the spleen as this is the major organ where platelets are stored outside of the circulation. Examples include:
  • Artefactual or spurious thrombocytopaenia
    • Cavalier King Charles spaniels have a relatively small number of giant platelets (macrothrombocytes) but they do not suffer from bleeding disorders as they maintain a similar total platelet mass as do dogs of other breeds.
    • If venepuncture is traumatic, platelet clumps may form and these will not be counted by automated machines. The presence of clumps can be investigated by making a blood smear and examining the feathered edge for large agglomerations of platelets.

Thrombocytopathia

Defects in platelet function may be congenital defects or they may be acquired with a number of diseases. Congenital thrombocytopathias are rare inherited diseases which are characterised by defects in platelet adhesiveness, aggregation and factor release. The defects are usually associated with particular breeds, such as Chediak-Higashi syndrome in blue smoke Persian cats.

Causes of acquired thrombocytopathia include:


Thrombocytosis

Increases in platelets above the normal level may occur due to physiological or pathological processes.

  • Physiological
    • Splenic contraction pushes sequestered platelets into the circulation. This phenomenon is especially marked in horses which have a muscular splenic capsule.
    • Splenectomy prevents the sequestration of platelets in the spleen, resulting in constantly increased levels of platelets.
    • As part of a response to anaemia, a reactive thrombocytosis is often documented and this may precede signs of regeneration.
  • Pathological
    • Essential thrombocythaemia
    • Megakaryocytic leukaemia
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