A 23-year-old woman has bled heavily after a tooth extraction and after childbirth. Results: platelets 248 × 10^3/µL (248 × 10^9/L) with normal size; PT, APTT, fibrinogen, factor XIII, VWF antigen and VWF activity all normal. Light transmission aggregation is normal with ADP, collagen, epinephrine, arachidonic acid and ristocetin. Flow cytometry after stimulation with thrombin plus collagen shows normal P-selectin expression, but annexin V binding is 15% of a normal control. Prothrombin consumption during clotting is reduced, leaving much prothrombin in her serum. Which step of the cell-based model of coagulation is defective?

Phosphatidylserine exposure on activated platelets

Platelet aggregation via GPIIb/IIIa and fibrinogen

Alpha-granule secretion during amplification

Platelet adhesion to VWF through GPIb-IX-V

Tissue factor pathway inhibitor (TFPI) shuts down the initiation phase by binding:

Factor Xa and then the TF-VIIa complex

Factors Va and VIIIa on platelets

High-dose recombinant factor VIIa can stop bleeding in hemophilia with inhibitors. According to the cell-based model, it works mainly by:

Activating factor X directly on activated platelets

Replacing factor VIII in the tenase complex

Neutralizing the antibody to factor VIII

Blocking tissue factor pathway inhibitor

Physiology: coagulation pathways, fibrinolysis, vascular system

19 ASCP MLS practice questions on Physiology: coagulation pathways, fibrinolysis, vascular system, part of Hematology. The first 19 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 23-year-old woman has bled heavily after a tooth extraction and after childbirth. Results: platelets 248 × 10^3/µL (248 × 10^9/L) with normal size; PT, APTT, fibrinogen, factor XIII, VWF antigen and VWF activity all normal. Light transmission aggregation is normal with ADP, collagen, epinephrine, arachidonic acid and ristocetin. Flow cytometry after stimulation with thrombin plus collagen shows normal P-selectin expression, but annexin V binding is 15% of a normal control. Prothrombin consumption during clotting is reduced, leaving much prothrombin in her serum. Which step of the cell-based model of coagulation is defective?
1. APhosphatidylserine exposure on activated platelets
2. BPlatelet aggregation via GPIIb/IIIa and fibrinogen
3. CAlpha-granule secretion during amplification
4. DPlatelet adhesion to VWF through GPIb-IX-V
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Answer: A · Phosphatidylserine exposure on activated platelets
In the cell-based model, the propagation phase needs activated platelets to move phosphatidylserine to their outer surface, where the tenase and prothrombinase complexes assemble. Annexin V binds exposed phosphatidylserine, so its low binding, together with poor prothrombin consumption, shows that this procoagulant surface is missing; this is Scott syndrome, a rare inherited defect of the scramblase TMEM16F. Normal ristocetin aggregation rules out an adhesion defect such as Bernard-Soulier syndrome, and normal aggregation with the other agonists rules out Glanzmann thrombasthenia. Normal P-selectin shows that alpha-granule secretion is intact. Routine clotting tests are normal because their reagents supply phospholipid.
- B: Aggregation with ADP, collagen, epinephrine and arachidonic acid is normal, so GPIIb/IIIa works.
- C: P-selectin, an alpha-granule membrane protein, appears normally on stimulated platelets.
- D: Ristocetin aggregation is normal, so GPIb-IX-V binding to VWF works.
Question 2 · Easy
One step of the intrinsic pathway is missing from the cascade diagram. Which factor should fill the gap?
Figure: MedExams
1. AFactor IX
2. BFactor V
3. CFactor VII
4. DFactor XIII
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Answer: A · Factor IX
In the classic intrinsic pathway, factor XIIa activates factor XI, and factor XIa activates factor IX. Factor IXa, with its cofactor VIIIa, calcium and phospholipid (the tenase complex), then activates factor X. A lack of factor IX is hemophilia B, which prolongs the APTT but not the PT. Factor VII belongs to the extrinsic pathway, factor V is the cofactor in prothrombinase, and factor XIII cross-links fibrin.
- B: Factor V is the cofactor for Xa in the prothrombinase complex.
- C: Factor VII works with tissue factor in the extrinsic pathway.
- D: Factor XIII cross-links fibrin at the end of the cascade.
Question 3 · Easy
In the classic cascade model, the common pathway is made up of factors:
1. AXII, XI, IX and VIII
2. BX, V, II and I
3. CII, VII, IX and X
4. DV, VIII, XI and XIII
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Answer: B · X, V, II and I
The intrinsic and extrinsic pathways both lead to activation of factor X, where the common pathway begins. Factor Xa with its cofactor Va converts prothrombin (II) to thrombin, and thrombin converts fibrinogen (I) to fibrin. Both the PT and the aPTT therefore detect deficiencies of X, V, II and fibrinogen. The cascade model fits test-tube results well but explains hemostasis in the body less well than the cell-based model.
- A: XII, XI, IX and VIII make up the intrinsic pathway.
- C: II, VII, IX and X are the vitamin K-dependent factors.
- D: V, VIII, XI and XIII are the factors that thrombin activates.
Question 4 · Medium
Tissue factor pathway inhibitor (TFPI) shuts down the initiation phase by binding:
1. AFactor Xa and then the TF-VIIa complex
2. BPlasmin and then plasminogen
3. CFactors Va and VIIIa on platelets
4. DThrombin and then fibrinogen
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Answer: A · Factor Xa and then the TF-VIIa complex
TFPI is made mainly by endothelial cells and is also carried in platelets. It first binds and inhibits factor Xa, and the TFPI-Xa pair then binds and inhibits the tissue factor-VIIa complex. Once some Xa has formed, this switches off the tissue factor route, so continued Xa production depends on factors IXa and VIIIa. Protein S enhances TFPI activity.
- B: Plasmin is inhibited by alpha2-antiplasmin; TFPI does not act on fibrinolysis.
- C: Factors Va and VIIIa are inactivated by activated protein C.
- D: Thrombin is inhibited mainly by antithrombin, and fibrinogen is its substrate.
Question 5 · Hard
High-dose recombinant factor VIIa can stop bleeding in hemophilia with inhibitors. According to the cell-based model, it works mainly by:
1. AActivating factor X directly on activated platelets
2. BReplacing factor VIII in the tenase complex
3. CNeutralizing the antibody to factor VIII
4. DBlocking tissue factor pathway inhibitor
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Answer: A · Activating factor X directly on activated platelets
At normal plasma levels, factor VIIa works only when bound to tissue factor. At pharmacologic doses it binds weakly to the phosphatidylserine of activated platelets and activates factor X there, independent of tissue factor. This bypasses the missing IXa-VIIIa tenase, so the thrombin burst can occur despite the inhibitor. Because it does not use factor VIII, the inhibitor titer does not reduce its effect.
- B: Factor VIIa is an enzyme, not a cofactor, so it cannot stand in for VIIIa.
- C: Recombinant VIIa does not bind or remove the anti-factor VIII antibody.
- D: Blocking TFPI is how a different class of drugs, the anti-TFPI antibodies, works.
Question 6 · Easy
Which activated factor forms covalent cross-links between fibrin molecules to stabilize the clot?
1. AFactor Xa
2. BFactor XIIa
3. CFactor XIIIa
4. DThrombin (factor IIa)
Answer and explanation in LearnFree account
Question 7 · Medium
In the cell-based model of coagulation, the burst of thrombin in the propagation phase is produced mainly on the surface of:
1. AActivated platelets at the injury site
2. BIntact endothelial cells
3. CTissue factor-bearing cells
4. DCirculating red cells
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Question 8 · Easy
Which substance released by intact endothelial cells inhibits platelet aggregation?
1. AThromboxane A2
2. BVon Willebrand factor
3. CPlasminogen activator inhibitor-1
4. DProstacyclin (PGI2)
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Question 9 · Easy
Plasminogen bound to fibrin is converted to plasmin mainly by:
1. ATissue plasminogen activator
2. BPlasminogen activator inhibitor-1
3. CThrombin-activatable fibrinolysis inhibitor
4. DAlpha2-antiplasmin
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Question 10 · Medium
The prothrombinase complex, which converts prothrombin to thrombin, is made up of:
1. AVIIa, tissue factor and calcium
2. BXIIa, prekallikrein and HMWK
3. CIXa, VIIIa, calcium and phospholipid
4. DXa, Va, calcium and phospholipid
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Question 11 · Medium
In the amplification phase of the cell-based model, the small amount of thrombin formed during initiation activates:
1. AProtein C and plasminogen
2. BFactor XII and prekallikrein
3. CPlatelets and factors V, VIII and XI
4. DFactors II, VII, IX and X
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Question 12 · Hard
Patients with severe hemophilia A have a normal tissue factor pathway and a normal PT, yet they bleed. Which explanation fits the cell-based model?
1. AFactor VIII is the cofactor in the prothrombinase complex
2. BTFPI stops TF-VIIa early, so Xa must come from IXa-VIIIa
3. CFactor VIII is needed for platelet adhesion to collagen
4. DFactor VIII is needed to activate factor VII
Answer and explanation in LearnFree account
Question 13 · Easy
Heparan sulfate on the surface of endothelial cells helps keep blood fluid by speeding up the action of:
1. AAntithrombin
2. BThrombomodulin
3. CProtein S
4. DAlpha2-antiplasmin
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Question 14 · Easy
In the body, coagulation is mainly started when circulating factor VIIa binds to:
1. AHigh-molecular-weight kininogen
2. BThrombomodulin
3. CTissue factor on subendothelial cells
4. DVon Willebrand factor
Answer and explanation in LearnFree account
Question 15 · Hard
Patient 1 has severe factor XII deficiency with an aPTT over 120 seconds, yet has had major surgery without bleeding. Patient 2 has factor XI deficiency and bleeds after a tooth extraction. What best explains the difference?
1. AFactor XI is the cofactor for factor IXa
2. BThrombin activates factor XI on platelets in vivo
3. CTissue factor-VIIa activates factor XI directly
4. DFactor XI is part of the common pathway
Answer and explanation in LearnFree account
Question 16 · Medium
Why does tissue plasminogen activator work much better on a clot than in free plasma?
1. AThrombin activates tPA within the clot
2. BtPA and plasminogen both bind to fibrin
3. CPlasminogen circulates only in platelets
4. DtPA is released only from inside the clot
Answer and explanation in LearnFree account
Question 17 · Medium
Besides factor X, the tissue factor-VIIa complex directly activates factor:
1. AXI
2. BXII
3. CIX
4. DVIII
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Question 18 · Medium
When thrombin binds to thrombomodulin on intact endothelium, what does its main action become?
1. ACleaving fibrinogen
2. BActivating protein C
3. CActivating platelets
4. DActivating factor V
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Question 19 · Easy
When thrombin converts fibrinogen to fibrin, it splits off:
1. AD-dimer fragments
2. BProthrombin fragment 1+2
3. CFibrinopeptides A and B
4. DFragments D and E
Answer and explanation in LearnFree account

Physiology: coagulation pathways, fibrinolysis, vascular system

One step of the intrinsic pathway is missing from the cascade diagram. Which factor should fill the gap?

In the classic cascade model, the common pathway is made up of factors:

Tissue factor pathway inhibitor (TFPI) shuts down the initiation phase by binding:

High-dose recombinant factor VIIa can stop bleeding in hemophilia with inhibitors. According to the cell-based model, it works mainly by:

Which activated factor forms covalent cross-links between fibrin molecules to stabilize the clot?

In the cell-based model of coagulation, the burst of thrombin in the propagation phase is produced mainly on the surface of:

Which substance released by intact endothelial cells inhibits platelet aggregation?

Plasminogen bound to fibrin is converted to plasmin mainly by:

The prothrombinase complex, which converts prothrombin to thrombin, is made up of:

In the amplification phase of the cell-based model, the small amount of thrombin formed during initiation activates:

Patients with severe hemophilia A have a normal tissue factor pathway and a normal PT, yet they bleed. Which explanation fits the cell-based model?

Heparan sulfate on the surface of endothelial cells helps keep blood fluid by speeding up the action of:

In the body, coagulation is mainly started when circulating factor VIIa binds to:

Patient 1 has severe factor XII deficiency with an aPTT over 120 seconds, yet has had major surgery without bleeding. Patient 2 has factor XI deficiency and bleeds after a tooth extraction. What best explains the difference?

Why does tissue plasminogen activator work much better on a clot than in free plasma?

Besides factor X, the tissue factor-VIIa complex directly activates factor:

When thrombin binds to thrombomodulin on intact endothelium, what does its main action become?

When thrombin converts fibrinogen to fibrin, it splits off: