Assessment

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Coagulation disorders and lab findings

Condition
PT
APTT
Bleeding time
Platelet count
Warfarin or Vit K deficiency
Prolonged
Normal or mildly Prolonged
Normal
Normal
DIC
Prolonged
Prolonged
Prolonged
Reduced
Uremia
Normal
Normal
Prolonged
Normal
Aspirin/Clopidogrel
Normal
Normal
Prolonged
Normal
Thrombocytopenia
Normal
Normal
Prolonged
Reduced
Liver failure
Prolonged
Normal or Prolonged
Normal or Prolonged
Normal or Reduced
Von Willebrand’s disease
Normal
Normal or Prolonged
Prolonged
Normal
Factor V deficiency
Prolonged
Prolonged
Normal
Normal
Hemophilia
Normal
Prolonged
Normal
Normal
Factor XII deficiency
Normal
Prolonged
Normal
Normal
Glanzmann’s thrombasthenia
Normal
Normal
Prolonged
Normal
  • PT monitors extrinsic and common pathway, reflecting activity of factors I, II, V, VII and X.
  • PTT monitors intrinsic and common pathway, reflecting activity of all factors except VII and XIII.
  • Bleeding time assesses platelet function.

Test

  • Basic
    • PT and INR = extrinsic

      • Thromboplastin is added to blood to activate the extrinsic pathway. Clotting time is measured in seconds (PT). This is compared to the normal value (12–13s) to get the INR for ease of comparison (normal 0.8–1.2).
      • Aid to memoire: WEPT – Warfarin Extrinsic Prothrombin Time
      • Prior to the common pathway, only factor 7 is involved (isolated deficiencies are rare), so PT/INR is only really affected by global reduced clotting factor synthesis or increased consumption
        • Warfarin/vitamin K deficiency
        • Liver disease
        • DIC

      APTT = intrinsic

      • Phospholipid, a contact activator, and calcium are added to blood to activate the intrinsic pathway. Clotting time is measured in seconds (normal = 30–50s).
      • Involves similar clotting factors to the extrinsic pathway plus some others (8, 9, 11) so affected by
        • Like the extrinsic path
          • Warfarin/vitamin K deficiency
          • Liver disease
          • DIC
        • PLUS anything which affects factors 8 (haemophilia A/Von Willebrand’s), factor 9 (haemophilia B), factor 11 (haemophilia C)
        • Notes
          • Factor 12 is also involved in the intrinsic pathway but deficiencies are rare
          • Anti-phospholipid syndrome is a common cause of a misleadingly prolonged APTT, due to antibody-mediated inactivation of the phospholipid added to activate the intrinsic pathway in the laboratory

      Bleeding time = platelet function

      • Involves making a patient bleed and timing how long it takes to stop
      • Measures platelet plug formation so only affected by conditions involving platelet quantity/function

      Thrombin time = fibrinogen test

      • Thrombin is added to blood to test the conversion of fibrinogen to fibrin to form a clot
      • This tests the level and function of fibrinogen

Coagulation assays and interpretation

Assay
Description
Interpretation
Thrombin clotting time (TT)
Thrombin added to anticoagulated (citrate/oxalate tube) blood and time to clot formation measured
Prolonged with heparin, fibrin degradation products and fibrinogen deficiency
Bleeding time
Not a laboratory test— involves making a cut in skin and measuring time for bleeding to stop. Has been replaced by platelet function assays
Prolonged in platelet dysfunction, but also other circumstances where bleeding tendency not reflected in laboratory tests (e.g. uremia)
Platelet function assay
Blood clotting assessed on collagen/epinephrine (Col/Epi) and collagen/ADP membranes. Normal Col/Epi closure time (< 180 s) excludes significant platelet function defect. If Col/Epi time prolonged, Col/ADP (Normal < 120 s) is automatically performed
Abnormal Col/Epi but normal Col/ADP suggests aspirin induced platelet dysfunction. Abnormal Col/Epi and Col/ADP suggests anemia, thrombocytopenia, or von Willebrand disease
INR/PT
Tests extrinsic + common pathway— factors I, II, V, VII and X. Performed by adding tissue factor (III) to anticoagulated sample and measuring time to clot formation. Each batch of tissue factor has differences; therefore this is standardized in INR
Prolonged PT due to vitamin K deficiency, warfarin, liver disease or DIC
Activated partial thromboplastin time (aPTT)
Tests intrinsic + common pathway I, II, V, VIII, IX, XI, XII— will be normal despite factor VII or XIII deficiency. Anticoagulated blood mixed with phospholipid, activator and calcium and time to clot formation measured. “Partial” = absence of tissue factor (III) from mixture
Prolonged APTT suggests heparin, antiphospholipid antibody, factor deficiency or anti-factor antibodies
Mixing (50:50) study
Plasma of patient with abnormal PT/APTT mixed with normal plasma in 50:50 ratio
Correction of PT/APTT suggests factor deficiency. Persistence of abnormal PT/APTT suggests presence of inhibitor (warfarin, heparin, lupus anticoagulant, coagulation factor antibodies)
Factor V Leiden
Requires genetic test. Mutated factor V cannot be inactivated by Protein C
Dilute Russell’s viper venom time (aRVVT)
Test for lupus anticoagulant (antiphospholipid antibodies) as venom requires phospholipid for activation
Prolonged aRVVT as antiphospholipid antibodies impair venom activation