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PA20.1-2 | Normal Haemostasis — Part 4
Laboratory Tests: Mapping Pathways to Tests
Knowing which test measures which pathway arm is non-negotiable for interpreting bleeding disorder work-ups.
| Test | Pathway measured | What it detects |
|---|---|---|
| PT / INR | Extrinsic + Common | VII, X, V, II, I deficiency; warfarin effect; liver disease |
| aPTT | Intrinsic + Common | XII, XI, IX, VIII, X, V, II, I deficiency; heparin; lupus anticoagulant |
| Thrombin time (TT) | Final step only | Fibrinogen level/function; heparin effect; direct thrombin inhibitors |
| Platelet count | Primary haemostasis | Thrombocytopenia (quantitative defect) |
| Bleeding time / PFA-100 | Primary haemostasis | Platelet function, vWF (qualitative defect) |
| D-dimer | Fibrinolysis | Active clot turnover; screening for VTE, DIC |
| Fibrinogen level | Common pathway | DIC (consumed), liver disease, congenital afibrinogenaemia |
Key interpretive rules:
• Isolated prolonged PT → extrinsic (factor VII) or liver/warfarin
• Isolated prolonged aPTT → intrinsic (VIII, IX, XI, XII) or heparin or lupus anticoagulant
• Both prolonged → common pathway defect, severe liver disease, DIC, or combined factor deficiency
• Normal PT and aPTT + prolonged bleeding time → primary haemostasis defect (platelet or vWF)
• Normal PT, aPTT, and platelet count + post-trauma bleeding → factor XIII deficiency (cross-linking step)
SELF-CHECK
A 25-year-old man has a lifelong history of haemarthroses (joint bleeds). His platelet count is normal, bleeding time is normal, PT is normal, but aPTT is significantly prolonged. Mixing study corrects the aPTT. The most likely diagnosis is:
A. Haemophilia A or B
B. Von Willebrand disease
C. Factor VII deficiency
D. Lupus anticoagulant
Reveal Answer
Answer: A. Haemophilia A or B
Prolonged aPTT + normal PT + normal platelet count + correction on mixing study (meaning the deficiency is corrected by normal plasma, ruling out an inhibitor) in a male with haemarthroses points to haemophilia A (factor VIII deficiency) or haemophilia B (factor IX deficiency). Both are X-linked. von Willebrand disease typically causes mucocutaneous, not deep joint, bleeding. Factor VII deficiency prolongs only the PT. Lupus anticoagulant does not correct on mixing.
Putting It All Together: The Haemostatic Response Timeline
Understanding the sequence helps you predict which disorders disrupt which phase:
0–30 seconds: Vascular injury → vasoconstriction (endothelin-1, neurogenic) + exposure of subendothelial collagen and vWF
30 sec – 3 min: Platelet adhesion (GPIb–vWF) → activation (shape change, ADP/TxA₂ release) → aggregation (GPIIb/IIIa–fibrinogen) → loose platelet plug. Lab: bleeding time/PFA tests this phase.
1–5 min: Tissue factor exposed → extrinsic pathway initiated → small thrombin burst → amplification on platelet surface → propagation → massive thrombin generation → fibrin polymerisation → fibrin reinforces platelet plug. Lab: PT and aPTT test this phase.
Hours–days: Fibrinolysis (tPA → plasmin → FDPs/D-dimer) dissolves clot as wound heals. Natural anticoagulants (AT-III, Protein C/S, TFPI) prevent extension beyond the injury site.
Timeline of Hemostatic Response and Associated Laboratory Tests
SELF-CHECK
Which of the following correctly pairs a vitamin K–dependent factor with its function?
A. Factor VIII — pro-coagulant, vitamin K–dependent
B. Factor XI — pro-coagulant, vitamin K–dependent
C. Protein C — anticoagulant, vitamin K–dependent
D. von Willebrand factor — platelet adhesion, vitamin K–dependent
Reveal Answer
Answer: C. Protein C — anticoagulant, vitamin K–dependent
Protein C is vitamin K–dependent and functions as an anticoagulant (with Protein S as cofactor, it degrades Va and VIIIa). Factor VIII is not vitamin K–dependent — it circulates bound to vWF. Factor XI is in the intrinsic pathway but is not vitamin K–dependent. vWF is not vitamin K–dependent and is not part of the coagulation cascade.