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

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)]]

==Introduction==

==Introduction==

[[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>]]

    

    

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.

===Prothrombin Time===

===Prothrombin Time===

Prothrombin time (PT) gives an assessment of the extrinsic and common pathways by measuring the time necessary to generate fibrin after activation of factor VII³. It is performed by an automated analyser² using citrated plasma^{1, 3}. Blood should therefore be collected into a sodium citrate tube if prothrombin time is to be performed. In basic terms, the test procedure involves adding thromoplastin to the patient's plasma, warming, adding calcium and recording the time taken to clot¹.

Prothrombin time (PT) gives an assessment of the extrinsic and common pathways by measuring the time necessary to generate fibrin after activation of factor VII³. It is performed manually or by an automated analyser² using citrated plasma^{1, 3}. Blood should therefore be collected into a sodium citrate tube if prothrombin time is to be performed. For the manual test, as a quality control measure it is normal to undertake the test in a sample from an unaffected patient to compare the time taken to clot between the two samples - this will account for variables such as variations in the technique of performing the manual test. The test procedure involves adding rabbit brain thromoplastin to the patient's plasma once it has been warmed to 37⁰C and recording the time taken for the sample to clot¹.

A prolonged PT may reflect a factor deficiency or the presence of a circulating inhibitor of coagulation. Repeating the test using a mix of test plasma and "normal" plasma can help differentiate these possibilities: PT returns to normal limits when normal plasma is added to factor-deficient plasma, but no change is seen when this is added to plasma containing inibitors³. PT is more sensitive than APTT for factor deficiencies.  

A prolonged PT may reflect a factor deficiency or the presence of a circulating inhibitor of coagulation. Repeating the test using a mix of test plasma and "normal" plasma can help differentiate these possibilities: PT returns to normal limits when normal plasma is added to factor-deficient plasma, but no change is seen when this is added to plasma containing inibitors³. PT is more sensitive than APTT for factor deficiencies.  

PT is affected by abnormalities or deficiencies in coagulation factors I, II, VII or X, for example in DIC, liver disease, or poisoning with vitamin K antagonists. Inherited defects are possible. PT is also prolonged by the presence of circulating anticoagulants. Inhibitors are often directed at factor X or thrombin and can include fibrin degradation products or heparin³.

PT is affected by abnormalities or deficiencies in coagulation factors I, II, VII or X, for example in DIC, liver disease, endotoxaemia or poisoning with vitamin K antagonists. Inherited defects are possible. PT is also prolonged by the presence of circulating anticoagulants. Inhibitors are often directed at factor X or thrombin and include fibrin degradation products and heparin³. As factor VII has the shortest half-life of all the coagulation factors, if a patient is suffering a coagulation factor deficiency a prolonged PT is seen before a prolonged PTT as this factor is depleted most rapidly.

===Tests for Individual Clotting Factors===

===Tests for Individual Clotting Factors===

Some specialised laboratories offer tests for specific clotting factors. Blood is required to be collected into a sodium citrate tube.

Some specialised laboratories offer tests for specific clotting factors. A sodium citrate sample is required.

===Proteins Induced by Vitamin K Antagonism Test===

===Proteins Induced by Vitamin K Antagonism Test===

A latex agglutination test is available for fibrin degradation products (FDP). To perform the test, anti-FDP antibodies attached to latex particles are added to serial dilutions of test serum. If agglutination is seen at a particular dilution, the test is positive. The most dilute sample that agglutinates gives the overall result of the test. Normal values are between 1/4 and 1/16.

A latex agglutination test is available for fibrin degradation products (FDP). To perform the test, anti-FDP antibodies attached to latex particles are added to serial dilutions of test serum. If agglutination is seen at a particular dilution, the test is positive. The most dilute sample that agglutinates gives the overall result of the test. Normal values are between 1/4 and 1/16.

Although the test is simple to perform, interpretation may be challenging. This is because other small fragments involved in the homeostasis of fibrinogen and fibrin are measured by the test in addition to ''bona fide'' fibrin degradation products. In general, an increase in FDP correspons to increased fibrinolysis. This can be due to a local problem of fibrin generation such as thrombosis, trauma or chronic bleeding, or be related to a systemic process, usually DIC³.

Although the test is simple to perform, interpretation may be challenging. This is because other small fragments involved in the homeostasis of fibrinogen and fibrin are measured by the test in addition to ''bona fide'' fibrin degradation products. In general, an increase in FDP corresponds to increased fibrinolysis. This can be due to a local problem of fibrin generation such as thrombosis, trauma or chronic bleeding, or be related to a systemic process, usually DIC³.

[[File:CABI logo.jpg|left|90px]]

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==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]]