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PA20.1 | Normal Haemostasis — SDL Guide (Part 4)

Laboratory Tests: Mapping Pathways to Tests

A three-panel medical diagram maps PT/INR, aPTT, thrombin time, platelet count, and bleeding time/PFA-100 to coagulation and primary haemostasis pathways. — **Panel A:** Coagulation cascade with Extrinsic pathway, Intrinsic pathway, Common pathway, Factor VII, XII, XI, IX, VIII, X, V, II thrombin, I fibrinogen, fibrin clot, PT / INR, aPTT, and TT callouts.. **Panel B:** Reference table linking PT / INR, aPTT, and thrombin time to measured pathway arms and major abnormalities detected.. **Panel C:** Primary haemostasis testing with platelet plug formation, platelet count, bleeding time / PFA-100, platelet adhesion, platelet aggregation, vWF, and thrombocytopenia or qualitative platelet defects..

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

A four-stage timeline shows vascular injury progressing through vasoconstriction, platelet plug formation, fibrin reinforcement, and fibrinolysis with associated lab tests. — **Panel A:** Vascular injury, vasoconstriction, endothelial disruption, subendothelial collagen, von Willebrand factor, endothelin-1, neurogenic response. **Panel B:** Platelet adhesion, GPIb-vWF interaction, platelet activation, shape change, ADP release, TxA2 release, platelet aggregation, GPIIb/IIIa-fibrinogen bridge, loose platelet plug, bleeding time/PFA. **Panel C:** Tissue factor exposure, extrinsic pathway initiation, thrombin burst, amplification on platelet surface, propagation, fibrin polymerisation, fibrin mesh, reinforced platelet plug, PT, aPTT. **Panel D:** tPA, plasminogen, plasmin, fibrin breakdown, FDPs, D-dimer, AT-III, Protein C/S, TFPI, prevention of clot extension.

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 diagram showing the four phases of hemostatic response from vasoconstriction through fibrinolysis with associated laboratory tests. — **Single Panel:** Temporal phases: vasoconstriction (0-30s), primary hemostasis with platelet plug (30s-5min), secondary hemostasis with fibrin reinforcement (3-10min), fibrinolysis (hours-days); laboratory tests: bleeding time, PT, aPTT, D-dimer.

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.