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Also known as: '''''coagulation profile — clotting profile — clotting tests — tests of haemostasis

{{OpenPagesTop}}Also known as: '''''coagulation profile — clotting profile — clotting tests — tests of haemostasis

[[Image:Coagulation Cascade.jpg|thumb|right|350px|oagulation cascade. Source: Wikimedia Commons; Author: Joe D (2007)]]

[[Image:Coagulation Cascade.jpg|thumb|right|350px|Coagulation cascade. Source: Wikimedia Commons; Author: Joe D (2007)]]

[[Image:LH_Platelet_Histology.jpg|thumb|right|<center><p>'''Platelets'''</p>^{©RVC 2008}</center>]]

[[Image:LH_Platelet_Histology.jpg|thumb|right|<center><p>'''Platelets'''</p>^{©RVC 2008}</center>]]

Normally, [[Normal Mechanisms of Haemostatic Control|haemostastis]] is maintained by three key events:   

Normally, [[Normal Mechanisms of Haemostatic Control|haemostastis]] is maintained by three key events:   

    

    

Abnormalities can develop in any of the components of haemostasis. Disorders of primary haemostasis include [[Haemorrhagic_Disease_Pathophysiology#Vascular_Fragility|vessel defects]] (i.e. vasculitis), [[Platelet_Abnormalities#Thrombocytopaenia|thrombocytopenia]] (due to decreased production or increased destruction) and [[Platelet Abnormalities|abnormalities in platelet function]] (e.g. congenital defects). These lead to the occurence of multiple minor bleeds and prolonged bleeding times; petechial or ecchymotic [[Haemorrhage - Pathology|haemorrhages]] may be seen for example, on the skin and mucous membranes, or ocular bleeds may arise. Generally, intact secondary haemostasis prevents major haemorrhage in disorders of primary haemostasis. When secondary haemostasis is abnormal, [[Haemorrhage - Pathology|larger bleeds]] are frequently seen. Haemothorax, haemoperitoneum, or haemoarthrosis may occur, in addition to subcutaneous and intramuscular haemorrhages. Petechiae and ecchymoses are not usually apparent, as intact primary haemostasis prevents minor capillary bleeding. Examples of secondary haemostatic disorders include [[:Category:Coagulation Defects|clotting factor deficiencies]] (e.g. hepatic failure, vitamin K deficiency, hereditary disorders) and circulation of substances inhibitory to coagulation (FDPs in [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]], [[Systemic Lupus Erythematosus|lupus]] anticoagulant). If fibrinolysis is defective, thrombus formation and infarctions may result. Thrombus formation may be promoted by vascular damage, circulatory stasis or changes in anticoagulants or procoagulants. For example, ATIII may be decreased. This can occur by loss due to glomerular disease or accelerated consumption in disseminated intravascular coagulation or sepsis.

 

Abnormalities can develop in any of the components of haemostasis. Disorders of primary haemostasis include [[Haemorrhagic_Disease_Pathophysiology#Vascular_Fragility|vessel defects]] (i.e. vasculitis), [[Platelet_Abnormalities#Thrombocytopaenia|thrombocytopenia]] (due to decreased production or increased destruction) and [[Platelet Abnormalities|abnormalities in platelet function]] (e.g. congenital defects). These lead to the occurence of multiple minor bleeds and prolonged bleeding times; petechial or ecchymotic [[Haemorrhage|haemorrhages]] may be seen for example, on the skin and mucous membranes, or ocular bleeds may arise. Generally, intact secondary haemostasis prevents major haemorrhage in disorders of primary haemostasis. When secondary haemostasis is abnormal, [[Haemorrhage|larger bleeds]] are frequently seen. Haemothorax, haemoperitoneum, or haemoarthrosis may occur, in addition to subcutaneous and intramuscular haemorrhages. Petechiae and ecchymoses are not usually apparent, as intact primary haemostasis prevents minor capillary bleeding. Examples of secondary haemostatic disorders include [[:Category:Coagulation Defects|clotting factor deficiencies]] (e.g. hepatic failure, vitamin K deficiency, hereditary disorders) and circulation of substances inhibitory to coagulation (FDPs in [[Disseminated Intravascular Coagulation|disseminated intravascular coagulation]], [[Systemic Lupus Erythematosus|lupus]] anticoagulant). If fibrinolysis is defective, thrombus formation and infarctions may result. Thrombus formation may be promoted by vascular damage, circulatory stasis or changes in anticoagulants or procoagulants. For example, ATIII may be decreased. This can occur by loss due to glomerular disease or accelerated consumption in disseminated intravascular coagulation or sepsis.

It is therefore important that all aspects of haemostasis can be independently evaluated. This will help to identify the phase affected and to pinpoint what the abnormality is. There are tests available to assess primary haemostasis, secondary haemostasis and fibrinolysis.

It is therefore important that all aspects of haemostasis can be independently evaluated. This will help to identify the phase affected and to pinpoint what the abnormality is. There are tests available to assess primary haemostasis, secondary haemostasis and fibrinolysis.

The reference range given for platelet number is usually around 200-500x10⁹ per litre, although this varies depending on the laboratory equipment used. Clinical signs due to thrombocytopenia are not commonly encountered until the platelet count drops below 50x10⁹/l, when increased bleeding times may be seen. Haemorrhage during surgery becomes a concern with counts lower than 20x10⁹/l, and spontaneous bleeding arises when platelets are fewer than 5x10⁹/l². These cut-offs are lowered if platelet function is concurrently affected by other factors such as the use of non-steroidal anti-inflammatory drugs¹.

The reference range given for platelet number is usually around 200-500x10⁹ per litre, although this varies depending on the laboratory equipment used. Clinical signs due to thrombocytopenia are not commonly encountered until the platelet count drops below 50x10⁹/l, when increased bleeding times may be seen. Haemorrhage during surgery becomes a concern with counts lower than 20x10⁹/l, and spontaneous bleeding arises when platelets are fewer than 5x10⁹/l². These cut-offs are lowered if platelet function is concurrently affected by other factors such as the use of non-steroidal anti-inflammatory drugs¹.

 

The buccal mucosal bleeding time is a simple test that gives a rapid assessment of platelet function, providing platelet numbers are normal. If platelet numbers are below 50x10⁹/l, this test should not be performed since the results will be affected by thrombocytopenia, making them unreliable. The small wound inflicted may also not stop bleeding easily.

The buccal mucosal bleeding time is a simple test that gives a rapid assessment of platelet function, providing platelet numbers are normal. If platelet numbers are below 50x10⁹/l, this test should not be performed since the results will be affected by thrombocytopenia, making them unreliable. The small wound inflicted may also not stop bleeding easily.

Acquired platelet function abnormalities can be drug induced, for example by [[NSAIDs|non-steroidal anti-inflammatory drugs]]^2,3, or can be secondary to [[Uraemia|uraemia]]. Hereditary defects in platelet function also exist, and [[Coagulation_Factor_Deficiency#Von_Willebrand.27s_Disease|von Willebrand's disease]] is the most common of these.

Acquired platelet function abnormalities can be drug induced, for example by [[NSAIDs|non-steroidal anti-inflammatory drugs]]^2,3, or can be secondary to [[Uraemia|uraemia]]. Hereditary defects in platelet function also exist, and [[Coagulation_Factor_Deficiency#Von_Willebrand.27s_Disease|von Willebrand's disease]] is the most common of these.

The BMBT is influenced by all the aspects of this phase, including vasoconstriction, platelet adherence and plately aggregation. Although this makes BMBT an effective screening test for the vascular/platelet (primary) phase of haemostasis, it also means it is not purely a test for thrombocytopathia, as it is often considered: BMBT depends on an intact vasospastic response and adequate platelet numbers as well as platelet function³. BMBT is a fairly crude test, and has been found to be

The BMBT is influenced by all the aspects of this phase, including vasoconstriction, platelet adherence and plately aggregation. Although this makes BMBT an effective screening test for the vascular/platelet (primary) phase of haemostasis, it also means it is not purely a test for thrombocytopathia, as it is often considered: BMBT depends on an intact vasospastic response and adequate platelet numbers as well as platelet function³. BMBT is a fairly crude test, and has been found to be normal in some patients with a known platelet function disorder and vice versa³. The results of this test therefore should be interpreted with some caution.

normal in some patients with a known platelet function disorder and vice versa³. The results of this test therefore should be interpreted with some caution.

==Tests Evaluating Secondary Haemostasis==

==Tests Evaluating Secondary Haemostasis==

===Activated Clotting Time===

===Activated Clotting Time===

The activated clotting time (ACT) allows rapid evaluation of secondary haemostasis. The ACT is the time taken for 2ml of fresh whole blood to clot in a tube with a contact activator (diatomaceous earth²), but an automated analyser can perform a test with a similar principle. The reaction must occur at body temperature to give a reliable indication of haemostatic ability: this can be achieved by the use of a warm water bath, or in an emergency by holding the tubes under an arm. The normal ACT is 90-120 seconds and <75 seconds in dogs and cats respectively².

The activated clotting time (ACT) allows rapid evaluation of secondary haemostasis. The ACT is the time taken for 2ml of fresh whole blood to clot in a tube with a contact activator (diatomaceous earth²), but an automated analyser can perform a test with a similar principle. The reaction must occur at body temperature to give a reliable indication of haemostatic ability: this can be achieved by the use of a warm water bath, or in an emergency by holding the tubes under an arm.  

The contact activator used in the ACT test triggers the intrinsic pathway, and so ACT allows assessment of the intrinsic and common pathways. ACT will therefore be prolonged when factors I, II, V, VIII, IX, X, XI or XII are deficient or abnormal, such as in DIC, liver disease, vitamin K antagonist toxicosis or haemophilia A or B². Thrombocytopenia may also increase ACT.

The contact activator used in the ACT test triggers the intrinsic pathway, and so ACT allows assessment of the intrinsic and common pathways. ACT will therefore be prolonged when factors I, II, V, VIII, IX, X, XI or XII are deficient or abnormal, such as in DIC, liver disease, vitamin K antagonist toxicosis or haemophilia A or B². Thrombocytopenia may also increase ACT.

The APTT measures the time necessary to generate fibrin from activation of the intrinsic pathway³. It therefore assesses functionality of the components of the intrinsic and common pathways of coagulation. The test is performed on citrated plasma, and so blood should be collected into a sodium citrate tube if the APTT test is to be undertaken. Once a sample is obtained, factor XII is activated by an external agent that will not also activate factor VII, such as kaolin^{1, 3}. Since the intrinsic arm of the cascade requires platelet factors to function, the test also provides a phospholipid emuslion in place of these factors. Calcium is added, the preparation is incubated, and the time for clumping of kaolin is measured. Classically, partial thromboplastin time was measured after activation by contact with a glass tube, but use of an external activating agent in the newer, "activated" partial thromboplastin time method makes results more reliable³.

The APTT measures the time necessary to generate fibrin from activation of the intrinsic pathway³. It therefore assesses functionality of the components of the intrinsic and common pathways of coagulation. The test is performed on citrated plasma, and so blood should be collected into a sodium citrate tube if the APTT test is to be undertaken. Once a sample is obtained, factor XII is activated by an external agent that will not also activate factor VII, such as kaolin^{1, 3}. Since the intrinsic arm of the cascade requires platelet factors to function, the test also provides a phospholipid emuslion in place of these factors. Calcium is added, the preparation is incubated, and the time for clumping of kaolin is measured. Classically, partial thromboplastin time was measured after activation by contact with a glass tube, but use of an external activating agent in the newer, "activated" partial thromboplastin time method makes results more reliable³.

APPT evaluates the same pathways as ACT, and so will be prolonged by abnormalities or deficiencies in factors XII, XI, IX, VIII, X, V, II or I. However, APTT is not affected by thrombocytopenia and is also considered to be a more sensitive test than ACT: APTT becomes prolonged when 70% of a factor is depleted, compared to 90% depletion required to prolong the ACT. APTT can also be prolonged in the presence of a circulating inhibitor to any of the intrinsic pathway factors. To differentiate factor deficiency from inhibition, a "mixing study" can be performed where the test is repeated on a 1:1 mix of patient and normal plasma. Complete correction indicates a deficiency, and partial or no resolution shows that an inhibitor is present. This difference stems from the above mentioned fact that the APTT will be normal in the presence of 50% normal activity³.

APPT evaluates the same pathways as ACT, and so will be prolonged by abnormalities or deficiencies in factors XII, XI, IX, VIII, X, V, II or I. However, APTT is not affected  

 

 

 

 

 

|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Coagulation%22&occuring1=title&rowId=2&options2=AND&q2=tes*&occuring2=title&rowId=3&options3=AND&q3=&occuring3=freetext&x=65&y=9&publishedstart=yyyy&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Coagulation Tests publications]

 

 

 

 

==Tests Evaluating Fibrinolysis==

 

 

 

 

 

 

[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Coagulation%22&occuring1=title&rowId=2&options2=AND&q2=tes*&occuring2=title&rowId=3&options3=AND&q3=&occuring3=freetext&x=65&y=9&publishedstart=yyyy&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Coagulation Tests publications]

==Links==

==Links==

#[http://ahdc.vet.cornell.edu/clinpath/modules/coags/pivka.htm Cornell University Clinical Pathology Modules: Tests of Haemostasis - PIVKA]

#[http://ahdc.vet.cornell.edu/clinpath/modules/coags/pivka.htm Cornell University Clinical Pathology Modules: Tests of Haemostasis - PIVKA]

#Howard, M R and (2008) '''Haematology: an illustrated colour text''', ''Elsevier Health Sciences''.

#Howard, M R and (2008) '''Haematology: an illustrated colour text''', ''Elsevier Health Sciences''.

[[Category:Blood Samples and Coagulation Tests]]

[[Category:Blood Samples and Coagulation Tests]]