Screening models for cardiovascular drugs – antiaggregatory and anticoagulant agents MCQs With Answer

Screening models for cardiovascular drugs are essential for evaluating antiaggregatory and anticoagulant agents during preclinical and early clinical development. B. Pharm students should understand in vitro and in vivo models—platelet aggregation assays (light transmission aggregometry, whole blood impedance), flow cytometry (P‑selectin), thrombin generation assays, chromogenic anti‑Xa, PT/aPTT, and viscoelastic tests (TEG/ROTEM)—along with animal thrombosis models (ferric chloride, Rose Bengal, laser injury). These tools assess pharmacodynamics, mechanism of action, potency, and bleeding risk for agents like aspirin, P2Y12 inhibitors, GP IIb/IIIa antagonists, heparins, and DOACs. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which assay is considered the gold standard for measuring platelet aggregation in platelet‑rich plasma?

• Light transmission aggregometry
• Whole blood impedance aggregometry
• Flow cytometry for P‑selectin
• Thromboelastography (TEG)

Correct Answer: Light transmission aggregometry

Q2. Which screening model measures platelet aggregation in whole blood by detecting electrical resistance changes?

• Light transmission aggregometry
• Whole blood impedance aggregometry
• Chromogenic anti‑Xa assay
• Ecarin clotting time

Correct Answer: Whole blood impedance aggregometry

Q3. Which technique directly quantifies platelet activation markers such as P‑selectin and activated GPIIb/IIIa on single cells?

• Chromogenic anti‑Xa assay
• Flow cytometry
• Thrombin generation assay
• Ferric chloride thrombosis model

Correct Answer: Flow cytometry

Q4. Which test provides dynamic information on clot formation, strength, and lysis useful in anticoagulant evaluation?

• PT/INR
• Light transmission aggregometry
• Thromboelastography (TEG)/ROTEM
• Chromogenic anti‑Xa assay

Correct Answer: Thromboelastography (TEG)/ROTEM

Q5. Which routine coagulation test is most sensitive to vitamin K antagonist therapy and used clinically for monitoring warfarin?

• aPTT
• PT/INR
• Anti‑Xa assay
• Thrombin generation assay

Correct Answer: PT/INR

Q6. Which laboratory test is classically prolonged by therapeutic unfractionated heparin?

• PT/INR
• aPTT
• Chromogenic anti‑Xa (for LMWH)
• Light transmission aggregometry

Correct Answer: aPTT

Q7. Which assay is preferred to monitor low molecular weight heparin (LMWH) activity in plasma?

• PT/INR
• aPTT
• Chromogenic anti‑Xa assay
• Thromboelastography MA

Correct Answer: Chromogenic anti‑Xa assay

Q8. Which specialized clotting test is most specific for measuring direct thrombin inhibitors like dabigatran?

• Prothrombin time (PT)
• Chromogenic anti‑Xa assay
• Ecarin clotting time (ECT)
• Bleeding time

Correct Answer: Ecarin clotting time (ECT)

Q9. Which parameter from the thrombin generation assay reflects the total thrombin produced over time (overall thrombin potential)?

• Lag time
• Peak thrombin
• Endogenous thrombin potential (ETP)
• Clotting time

Correct Answer: Endogenous thrombin potential (ETP)

Q10. Which animal thrombosis model commonly induces arterial thrombosis by topical oxidative injury?

• Venous stasis model
• Ferric chloride (FeCl3) injury model
• Streptokinase infusion model
• Tail bleeding time model

Correct Answer: Ferric chloride (FeCl3) injury model

Q11. The Rose Bengal photochemical injury model creates thrombosis through generation of reactive oxygen species after illumination; it is primarily used to model what?

• Platelet function in vitro
• Photochemically induced arterial thrombosis in vivo
• Chromogenic substrate kinetics
• Inhibition of coagulation factor synthesis

Correct Answer: Photochemically induced arterial thrombosis in vivo

Q12. Laser‑induced endothelial injury is most useful in preclinical studies for which purpose?

• High‑throughput plate reader assays
• Intravital microscopy visualization of dynamic thrombus formation
• Measuring plasma anti‑Xa concentrations
• Assessing PT/INR variability

Correct Answer: Intravital microscopy visualization of dynamic thrombus formation

Q13. Which agonist is commonly used in aggregometry to probe aspirin’s inhibitory effect on platelet COX‑1 pathway?

• ADP
• Arachidonic acid
• Collagen
• Thrombin

Correct Answer: Arachidonic acid

Q14. Which agonist is typically used to assess responsiveness to P2Y12 inhibitors such as clopidogrel?

• ADP
• Arachidonic acid
• U46619 (thromboxane analog)
• Fibrinogen

Correct Answer: ADP

Q15. GP IIb/IIIa inhibitors block which key step in platelet‑mediated thrombosis?

• Thrombin generation
• Platelet adhesion to collagen
• Fibrinogen‑mediated platelet aggregation via GPIIb/IIIa receptor
• Vitamin K recycling

Correct Answer: Fibrinogen‑mediated platelet aggregation via GPIIb/IIIa receptor

Q16. In thromboelastography (TEG), which parameter represents maximum clot strength and is sensitive to platelet function and fibrinogen?

• R time
• K time
• MA (maximum amplitude)
• Alpha angle

Correct Answer: MA (maximum amplitude)

Q17. In ROTEM, which parameter is analogous to TEG’s MA and indicates maximum clot firmness?

• CT (clotting time)
• CFT (clot formation time)
• MCF (maximum clot firmness)
• Alpha angle

Correct Answer: MCF (maximum clot firmness)

Q18. Which TEG/ROTEM parameter predominantly reflects the enzymatic coagulation factor activity and time to initial fibrin formation?

• R time / CT
• MA / MCF
• K time / CFT
• Alpha angle

Correct Answer: R time / CT

Q19. Which laboratory method is the standard for quantitative fibrinogen measurement used in coagulation screening?

• Clauss fibrinogen assay
• Chromogenic anti‑Xa
• Bleeding time
• Flow cytometry for fibrinogen

Correct Answer: Clauss fibrinogen assay

Q20. What is the basic principle of a chromogenic anti‑Xa assay used for heparin/DOAC monitoring?

• Measuring platelet aggregation by light transmission
• Detecting residual factor Xa activity via a chromogenic substrate
• Quantifying thrombin generation potential
• Directly measuring fibrin clot firmness

Correct Answer: Detecting residual factor Xa activity via a chromogenic substrate

Q21. Compared with platelet‑rich plasma (PRP) aggregometry, one advantage of whole blood aggregometry is:

• Elimination of erythrocyte and leukocyte influences
• Preservation of cellular interactions including red cells and white cells
• Higher sensitivity to plasma clotting factors
• No requirement for anticoagulation during sampling

Correct Answer: Preservation of cellular interactions including red cells and white cells

Q22. A major practical limitation of light transmission aggregometry in drug screening is:

• Its suitability for high‑throughput automation
• The requirement for fresh platelet‑rich plasma and manual handling
• Its inability to detect aspirin effects
• Its exclusive use for anticoagulant drugs

Correct Answer: The requirement for fresh platelet‑rich plasma and manual handling

Q23. Why are routine PT and aPTT often insensitive for monitoring many direct oral anticoagulants (DOACs)?

• DOACs do not affect the coagulation cascade
• PT/aPTT reagents have variable sensitivity and lack linear correlation with DOAC concentration
• DOACs only affect platelet function, not coagulation
• PT/aPTT are only used for fibrinogen measurement

Correct Answer: PT/aPTT reagents have variable sensitivity and lack linear correlation with DOAC concentration

Q24. In preclinical antiplatelet screening, which primary endpoint best indicates antiaggregatory activity?

• Decrease in thrombin generation peak only
• Inhibition of agonist‑induced platelet aggregation
• Prolongation of PT
• Increase in fibrinogen concentration

Correct Answer: Inhibition of agonist‑induced platelet aggregation

Q25. In a thrombin generation assay, an anticoagulant effect is typically reflected by which change?

• Shorter lag time and increased peak thrombin
• Longer lag time and decreased endogenous thrombin potential (ETP)
• No change in parameters
• Isolated increase in fibrinogen level

Correct Answer: Longer lag time and decreased endogenous thrombin potential (ETP)

Q26. Which in vivo method allows continuous observation and measurement of thrombus formation in live animals at the microvascular level?

• Ex vivo clot retraction assay
• Intravital fluorescence microscopy after laser injury
• Chromogenic anti‑Xa on plasma
• In vitro platelet aggregometry

Correct Answer: Intravital fluorescence microscopy after laser injury

Q27. An increase in platelet surface P‑selectin measured by flow cytometry indicates what process?

• Decreased platelet count
• Platelet activation and alpha‑granule release
• Enhanced fibrinolysis
• Reduced thrombin generation

Correct Answer: Platelet activation and alpha‑granule release

Q28. On a TEG trace, a markedly reduced MA suggests which clinical lab issue relevant to bleeding risk?

• Hypercoagulability due to excess fibrinogen
• Platelet dysfunction or low fibrinogen causing reduced clot strength
• Isolated prolongation of initiation phase only
• Elevated thrombin generation potential

Correct Answer: Platelet dysfunction or low fibrinogen causing reduced clot strength

Q29. For high‑throughput screening of novel antiplatelet compounds in drug discovery, which platform is commonly adapted?

• Manual light transmission aggregometry only
• Microplate‑based aggregometry or high‑content impedance assays
• Chromogenic anti‑Xa assays
• Intravital microscopy in mice

Correct Answer: Microplate‑based aggregometry or high‑content impedance assays

Q30. Which circulating biomarker is often measured in vivo to indicate systemic thrombin generation and is useful in evaluating anticoagulant efficacy?

• D‑dimer only
• Thrombin–antithrombin (TAT) complexes
• Platelet count
• Bleeding time

Correct Answer: Thrombin–antithrombin (TAT) complexes

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