Basic Science Day 3 Factors

What triggers the intrinsic pathway, and what factors are involved in order?

Contact with damaged vessel wall/collagen; Factor XII → XI → IX (with Factor VIII acting as a cofactor to help IX activate X)

What triggers the extrinsic pathway, and what factors are involved?

Tissue Factor (Factor III) released from damaged tissue outside the vessel; Tissue Factor activates Factor VII

Where do intrinsic and extrinsic pathways converge, and what happens from there (the common pathway)?

Both converge at Factor X. Xa + Va + platelet phospholipid membrane form the prothrombinase complex → activates Factor II (prothrombin) → Thrombin (IIa) → converts Fibrinogen (I) → Fibrin → Factor XIIIa cross-links the fibrin to stabilize the clot

What does aPTT test, and which factor's deficiency does it detect?

Intrinsic + common pathway (factors XII, XI, IX, VIII, X, V, II, I); detects Factor VIII deficiency (Hemophilia A) as a prolonged result

What does PT/INR test, and which factor's deficiency does it detect?

Extrinsic + common pathway (factors VII, X, V, II, I); detects Factor VII deficiency as a prolonged result

What does TT (Thrombin Time) test specifically?

The final conversion of fibrinogen to fibrin by thrombin — the very last step of the common pathway, independent of which pathway triggered the cascade

What does bleeding time test, and what does a prolonged result indicate?

Platelet plug formation/function — a prolonged bleeding time indicates a PLATELET problem (adhesion, count, or function), not a clotting factor problem

Factor VIII belongs to which pathway, and what does its deficiency cause?

Intrinsic pathway; deficiency causes Hemophilia A — prolonged aPTT, normal PT, normal bleeding time

Factor VII belongs to which pathway, and what would isolated deficiency cause?

Extrinsic pathway; isolated deficiency causes a prolonged PT with normal aPTT and normal bleeding time

What lab pattern distinguishes von Willebrand Disease from Hemophilia A?

Both show prolonged aPTT (vWF normally stabilizes Factor VIII) — but vWD ALSO shows prolonged bleeding time (platelet adhesion defect), while Hemophilia A has a normal bleeding time. That combination of BOTH abnormal aPTT and abnormal bleeding time is the vWD signature.

What are the four vitamin K-dependent clotting factors?

II, VII, IX, X — mnemonic "1972" (the digits)

How does warfarin (Coumadin) work?

Blocks vitamin K, preventing proper activation (gamma-carboxylation) of factors II, VII, IX, X — PT prolongs first because Factor VII has the shortest half-life of the four, with aPTT prolonging later as the other factors deplete

Antithrombin III inactivates which two factors, and why those two specifically?

Factor II (thrombin) and Factor Xa — these sit at the shared convergence point of both pathways (the common pathway bottleneck), so targeting them shuts down clotting regardless of which pathway triggered it, rather than only blocking one route

What is heparin's mechanism of action?

Heparin potentiates (dramatically boosts) Antithrombin III's natural inhibitory activity against thrombin and Factor Xa — it doesn't act on its own or target a specific pathway

Does Antithrombin III directly inactivate Factor VIII? True or False

False — AT3 targets Factor II and Xa specifically, not intrinsic-pathway-specific factors like VIII or IX

What is Factor XIIIa's role, and what does it create?

Cross-links fibrin strands together to stabilize the clot — this cross-linking is what creates the D-dimer structure (two D domains bonded together)

What generates a measurable D-dimer in the blood, and by what two-step process?

Factor XIIIa's cross-linking creates the D-dimer bond structure within the fibrin clot; plasmin later breaks the clot apart (fibrinolysis), releasing the D-dimer fragment into circulation where it can be measured

What is plasmin's function?

Breaks down fibrin (fibrinolysis) once a clot is no longer needed

EXAM QUESTION: Which of the following is NOT involved in the activation of Factor II?

Factor VIII — it works one step earlier, helping activate Factor X, and is not part of the Xa/Va/platelet phospholipid complex that directly activates Factor II

EXAM QUESTION: Heparin-Antithrombin III complex is involved in the inactivation of which factor?

Factor II (thrombin) — along with Factor Xa

EXAM QUESTION: Best test to detect Factor VIII deficiency?

Activated partial thromboplastin time (aPTT) — since Factor VIII is intrinsic-pathway specific

EXAM QUESTION: A patient has prolonged aPTT, normal PT, and prolonged bleeding time. Which disease?

Von Willebrand Disease — the combination of both abnormal aPTT and abnormal bleeding time together

Practice: Which factor acts as a cofactor helping activate Factor X?

Factor VIII

Practice: A patient with Hemophilia A — what is the expected lab pattern?

Prolonged aPTT, normal PT, normal bleeding time

Practice: Which factor initiates the extrinsic pathway?

Tissue Factor (Factor III)

Practice: A patient on warfarin would show prolongation of which test first?

PT/INR — due to Factor VII's short half-life dropping first among the vitamin K-dependent factors

Practice: What is the role of the platelet phospholipid membrane in coagulation?

Provides the surface for the prothrombinase complex (Xa + Va) to assemble and activate Factor II

Practice: A patient has isolated prolonged PT/INR with a completely normal aPTT. Which factor deficiency fits?

Factor VII deficiency

Practice: Which factor is the first point where intrinsic and extrinsic pathways converge into the common pathway?

Factor X