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
- 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
- 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
- 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 is added to blood to test the conversion of fibrinogen to fibrin to form a clot
- This tests the level and function of fibrinogen
PT and INR = extrinsic
APTT = intrinsic
Bleeding time = platelet function
Thrombin time = fibrinogen test
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 |