Coagulation Testing
PT/APTT
PT | APTT | |
Factors Affected | I, II, V, VII, X
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All except VII - Congenital def. of VIII, IX, or XI - VWF disease → low VIII |
Pathways Affected | Extrinsic and common | Intrinsic and common |
Drugs Monitored | Coumadin (warfarin) | Heparin (unfractionated) |
Conditions |
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Interfering Factors |
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RI |
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Reflex/Follow-up Testing
Test (RI) | Info | Ordered When | |
Thrombin Time (15-20s) | Assesses deficiencies or dysfunction of fibrinogen (Factor I) or thrombin (Factor II) inhibitor Less fibrinogen available → longer clot time |
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Fibrinogen
(2.2-5.0 g/L) (Critical: <1.0g/L with increased PT, APTT, TT) |
Modified TT assay that estimates concentration of functional fibrinogen Clotting time correlates with active fibrinogen |
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D-Dimer | Measures fibrin clot breakdown products from plasmin Elevated D-dimer alone is non-specific except in VTE - Can be associated with a variety of diseases or inflammatory states
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Mixing Studies | |||
dRVVT | Assesses | ||
Inhibitor Testing | |||
Factor Assays |
Abnormal Results
If PT/INR and APTT both prolonged
- Multiple factors in intrinsic and extrinsic pathways affected OR single factor deficiency in common pathway (I, II, V, or X [I if severe])
- Congenital:
- Single factor deficiency for factor I, II, V, or X
- Acquired:
- Multiple factor deficiency in intrinsic AND extrinsic pathways
- Severe liver disease
- Severe Vitamin K deficiency
- DIC
- Specific inhibitor directed to common pathway factor
- Hypofibrinogenemia/dysfibrinogenemia
- Massive hemmorage
- Congenital
- Fibrinolysis
- Multiple factor deficiency in intrinsic AND extrinsic pathways
If PT/INR is prolonged, but APTT is normal
- Probably related to factor VII
- Congenital single factor VII deficiency
- Acquired
- Early liver disease
- Early vitamin K deficiency
- Early coumadin therapy or initial dose
- Specific inhibitor to VII (rare)
If APTT is prolonged, but PT/INR is normal
- Probably related to intrinsic pathway factors VIII, IX, XI, or contact factors
- Congenital
- Single factor deficiency of VIII, IX, XI with bleeding (hemophilia A, B, or C respectively)
- VWD (can lead to factor VIII deficiency)
- Deficiency of factor XII, pre-K, HMWK (contact factors)
- Prolongs APTT but doesn’t result in clinically significant bleeding
- Acquired
- Non-specific inhibitor (e.g., antiphospholipid antibodies)
- Lupus anticoagulant in SLE patients
- Specific inhibitor against intrinsic factors
- Hemophilia patients may develop anti-FVIII or IX due to treatment
- Acquired hemophilia or acquired VWD
- Heparin therapy
- Non-specific inhibitor (e.g., antiphospholipid antibodies)
- Congenital
Causes of Abnormal Results + Followup Testing
Test Affected | Cause | Disease States | Symptoms/Patient History | Pathways Affected | Followup Testing |
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BOTH PT and APTT | Single factor deficiency for I, II, V, or X |
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Multiple factor deficiency in intrinsic AND extrinsic pathways | Severe liver disease | Jaundice, abdominal pain or tenderness |
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Severe Vitamin K deficiency |
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Disseminated intravascular coagulation |
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Specific inhibitor to common pathway factor | |||||
Hypofibrinogenemia/dysfibrinogenemia |
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PT only | Factor VIII deficiency | Congenital single factor VII deficiency | |||
Early liver disease | |||||
Early Vitamin K deficiency | |||||
Early coumadin therapy/initial dose | Normal when on coumadin | ||||
Specific inhibitor to VIII (rare) | |||||
APTT only | VWF disease |
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Factor VIII |
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Hemophilia A, B, or C (single factor deficiency) |
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Other congenital factor deficiencies |
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Non-specific inhibitor | Lupus Anticoagulant/Antiphospholipid Syndrome (Autoimmune disease) |
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Heparin therapy | Normal when patient is on heparin. Can also be caused by specimen contamination with heparin. | ||||
Other drugs | Rivaroxaban, apixaban, edoxaban | ||||
Specific inhibitor against intrinsic factors |
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Other disorders that may not affect PT/APTT include:
- Deficiencies
- Antithrombin
- Protein C
- Free PS
- TPA
- Mutations
- Factor V (Factor V Leiden APCR)
- Prothrombin (G20210A)
- Fibrinogen (dysfribrinogenemia)
- Plasminogen
- PAI-1 (elevation)
Investigating Abnormal Results
- Check specimen integrity and HCT
- Correct anticoagulant (sodium citrate)
- Proper tube filling (9:1 ratio, within 10% of fill volume)
- If HCT >55% (recollect sample using calculated dilution)
- Check patient history for any conditions affecting coagulation. If present, report results:
- Anticoagulant therapy: warfarin/coumadin, heparin, direct oral anticoagulants (DOACs)
- Liver disease (early: PT, late: both PT/APTT)
- Vitamin K deficiency
- Known factor deficiency (single or multiple)
- Look for other causes and perform reflex testing
- Decreased fibrinogen → Thrombin time or fibrinogen assay
- Specific single or multiple factor deficiency
- Inhibitor or antibody to factors
- Inhibitor or antibody interfering with test