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==Tests Evaluating Secondary Haemostasis==
 
==Tests Evaluating Secondary Haemostasis==
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Secondary hemostasis describes the formation of a cross linked fibrin meshwork in the blood clot and is dependent on the soluble coagulation factors. Abnormalities in secondary coagulation can occur from insufficient coagulation factors or the presence of inactive coagulation factors. The soluble coagulation factors are traditionally divided into the intrinsic, extrinsic and common pathways, as described in the introduction.
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Secondary haemostasis describes the formation of a cross linked fibrin meshwork in the blood clot and is dependent on soluble coagulation factors. Abnormalities in secondary coagulation can occur from insufficient coagulation factors, the presence of inactive coagulation factors or inhibition of factors. The soluble coagulation factors are traditionally divided into the intrinsic, extrinsic and common pathways, as described in the introduction.
    
===Activated Clotting Time===
 
===Activated Clotting Time===
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===Activated Partial Thromboplastin Time===  
 
===Activated Partial Thromboplastin Time===  
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The APTT is measures the time necessary to generate fibrin from activation of the intrinsic pathway<sup>3</sup>. 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<sup>,1 3</sup>. 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 reliable<sup>3</sup>.
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The APTT is measures the time necessary to generate fibrin from activation of the intrinsic pathway<sup>3</sup>. 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<sup>1, 3</sup>. 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 reliable<sup>3</sup>.
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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, 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 of 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 activity<sup>3</sup>.
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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 of 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 activity<sup>3</sup>.
    
Conditions in which APTT is prolonged include inherited disorders, such as haemophilia A and B and other congential absences of intrinsic and common factors. Acquired factor deficiency also occurs, for example with vitamin K deficiency, liver dysfunction, prolonged bleeding or disseminated intravascular coagulation. The most common inhibitors found to prolong APTT are the antithrombins, which inhibit the activity of thrombin on the conversion of fibrinogen to fibrin. Examples include heparin and fibrin degradation products.
 
Conditions in which APTT is prolonged include inherited disorders, such as haemophilia A and B and other congential absences of intrinsic and common factors. Acquired factor deficiency also occurs, for example with vitamin K deficiency, liver dysfunction, prolonged bleeding or disseminated intravascular coagulation. The most common inhibitors found to prolong APTT are the antithrombins, which inhibit the activity of thrombin on the conversion of fibrinogen to fibrin. Examples include heparin and fibrin degradation products.
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