ASCP Coagulation 1 — Questions and Answers

Question 1: Which coagulation factor is also known as the Leiden variant when mutated, leading to activated protein C resistance?

Factor II
Factor V (Correct answer)
Factor VIII
Factor X

Correct answer: Factor V

Factor V Leiden is a mutated form of Factor V where arginine 506 is replaced by glutamine, making it resistant to cleavage and inactivation by activated protein C. This is the most common inherited thrombophilia.

Factor V Leiden results from a point mutation (G1691A) in the F5 gene. Normally, activated protein C (APC) cleaves and inactivates Factor Va at Arg506. In Factor V Leiden, this cleavage site is abolished, so Factor Va remains active longer, promoting thrombosis. Heterozygotes have 3–8× increased VTE risk; homozygotes 50–80×.

Question 2: The PT (prothrombin time) primarily evaluates which coagulation pathway?

Intrinsic pathway
Extrinsic pathway (Correct answer)
Common pathway only
Fibrinolytic pathway

Correct answer: Extrinsic pathway

PT evaluates the extrinsic and common pathways, testing factors VII, X, V, II, and fibrinogen. It is initiated by tissue factor (thromboplastin) added in the reagent.

The PT is performed by adding tissue factor (thromboplastin) and calcium to citrated plasma. Tissue factor activates Factor VII, initiating the extrinsic pathway. The cascade proceeds through Factor X to Factor II (prothrombin) to thrombin to fibrin. Factors evaluated: VII, X, V, II, fibrinogen. Normal PT: approximately 11–13 seconds. The INR normalizes PT for anticoagulation monitoring.

Question 3: Which laboratory test is most specific for monitoring unfractionated heparin therapy?

PT/INR
aPTT (Correct answer)
Anti-Xa assay
Thrombin time

Correct answer: aPTT

The aPTT (activated partial thromboplastin time) is the standard monitoring test for unfractionated heparin (UFH). Therapeutic range is typically 1.5–2.5 times baseline (60–100 seconds).

Heparin binds antithrombin (AT) and accelerates inhibition of thrombin (Factor IIa), Factor Xa, IXa, XIa, and XIIa. The aPTT measures the intrinsic plus common pathways (Factors XII, XI, IX, VIII, X, V, II, fibrinogen) and is prolonged by heparin. Anti-Xa is increasingly used for monitoring low-molecular-weight heparin and obese patients, but aPTT remains first-line for UFH.

Question 4: D-dimer is a fibrin degradation product that indicates:

Platelet activation
Clot formation AND fibrinolysis (Correct answer)
Vitamin K deficiency
Heparin effect

Correct answer: Clot formation AND fibrinolysis

D-dimer is formed when plasmin degrades cross-linked fibrin. Its elevation indicates both thrombus formation (cross-linked fibrin was made) and fibrinolysis (that fibrin is being broken down).

Cross-linked fibrin forms when thrombin cleaves fibrinogen and Factor XIIIa cross-links the fibrin polymers. Plasmin then degrades these cross-linked fibers, releasing D-dimer fragments. D-dimer has high sensitivity but low specificity for VTE, making it useful for ruling out DVT/PE. Elevated D-dimer also occurs in DIC, surgery, malignancy, pregnancy, and inflammation.

Question 5: In disseminated intravascular coagulation (DIC), which set of laboratory findings is most characteristic?

Low PT, high platelets, high fibrinogen
High PT, low platelets, low fibrinogen, high D-dimer (Correct answer)
Normal PT, normal aPTT, high D-dimer only
High fibrinogen, normal D-dimer, low PT

Correct answer: High PT, low platelets, low fibrinogen, high D-dimer

DIC is characterized by simultaneous clotting and fibrinolysis: PT and aPTT are prolonged (factor consumption), platelets are low (consumed), fibrinogen is low (consumed), and D-dimer is elevated (fibrinolysis).

DIC is triggered by systemic thrombin generation from sepsis, trauma, obstetric emergencies, or malignancy. Massive clot formation consumes platelets, fibrinogen, and coagulation factors II, V, and VIII, prolonging PT and aPTT. Reactive fibrinolysis elevates D-dimer and FDPs. Schistocytes appear on the blood smear due to microangiopathic hemolytic anemia. Treatment addresses the underlying cause.

Question 6: Which von Willebrand disease (vWD) subtype is characterized by the absence of high-molecular-weight multimers and is inherited in an autosomal dominant pattern?

Type 1 vWD
Type 2A vWD (Correct answer)
Type 2B vWD
Type 3 vWD

Correct answer: Type 2A vWD

Type 2A vWD shows absence of high- and intermediate-molecular-weight multimers, resulting in decreased platelet adhesion. It is autosomal dominant and represents a qualitative defect in vWF.

vWF multimers vary in size; the large multimers are most effective at mediating platelet adhesion via GPIb. In Type 2A vWD, mutations cause abnormal vWF that is missing high-molecular-weight multimers through increased susceptibility to ADAMTS13 cleavage or impaired multimerization. Lab findings: ristocetin cofactor activity reduced, normal or reduced vWF antigen, abnormal multimer analysis. Type 2B causes increased affinity for GPIb with loss of HMW multimers due to spontaneous platelet binding.

ASCP Coagulation 1

Which coagulation factor is also known as the Leiden variant when mutated, leading to activated protein C resistance?