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Interpretation of the results of screening tests used in the diagnosis of coagulation disorders

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Interpretation of results of screening tests used in the diagnosis of coagulation disorders

Screening tests	Abnormalities indicated by prolongation of screening test result	Examples of causes of prolongation of screening test
thrombin time - this test is sensitive to a deficiency of fibrinogen or inhibition of thrombin.	abnormalities in thrombin time indicate an abnormality or deficiency of fibrinogen, OR, inhibition of thrombin by heparin or fibrin degradation products (FDPs)	disseminated intravascular coagulation heparin therapy
prothrombin time - measures the extrinsic system (also known as the tissue factor pathway) (factor VII) as well as factors that are common to both systems (factor X, V, prothrombin and fibrinogen). The normal prothrombin time for clotting is 10-14 seconds. It may be expressed as the international normalized ratio (INR).	abnormalities in prothrombin time indicate an inhibition or deficiency of one or more of the following coagulation factors: factor II (prothrombin), V, VII, X, fibrinogen The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. Factor VII has a short half-life and it requires vitamin K for synthesis.	Deficiencies in vitamin K, which can be caused by warfarin, malabsorption or lack of intestinal colonization by bacteria (such as in newborns) Reduced factor VII synthesis (due to liver disease) Increased consumption (in disseminated intravascular coagulation)
activated partial thromboplastin time (APTT) - this test measures the intrinsic system (also known as the contact activation pathway) factors VIII, IX, XI and XII as well as factors common to both systems (factors X, V, prothrombin and fibrinogen). Note that the term partial is used for this screening test due to the absence of tissue factor from the reaction mixture.	abnormalities in APTT indicate an inhibition or deficiency of one or more of the following factors: XII, IX, VIII, XI, X, V, II, fibrinogen	Haemophilia Other causes include: Heparin use (or contamination of the sample) Antiphospholipid antibody (especially lupus anticoagulant this leads to an increased propensity to thrombosis)

Notes:

if prolonged APTT
- to distinguish the cause of the prolonged APTT then mixing studies are performed
  - the patient's plasma is mixed (initially at a 50:50 dilution) with normal plasma
    - if the abnormality persists then the sample is said to contain an "inhibitor" (either heparin, antiphospholipid antibodies or coagulation factor specific inhibitors)
    - if the abnormality corrects after the mixing study is performed then a factor deficiency is more likely
      - a prolonged APTT may be caused by deficiencies of factors VIII, IX, XI and XII and rarely von Willebrand factor (if causing a low factor VIII level)

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