A 26-year-old woman develops a proximal deep vein thrombosis 4 months after starting a combined oral contraceptive. Her mother had a pulmonary embolism during pregnancy. A sample taken before any heparin was given shows: antithrombin activity (factor Xa-based) 47% (reference 80-120%), antithrombin antigen 49% (80-120%), protein C activity 98% (70-140%), free protein S antigen 84% (60-130%), APC-resistance ratio 2.6 (normal above 2.0) and factor VIII 118% (50-150%). Over the next 2 days she needs unusually high doses of unfractionated heparin before her APTT reaches the therapeutic range. Which conclusion best explains both the thrombosis and the poor heparin response?

Type I (quantitative) antithrombin deficiency

Antithrombin lowered by heparin therapy

Heparin resistance from a raised factor VIII

Type II antithrombin deficiency (heparin-binding site)

Anti-TFPI antibodies such as concizumab and marstacimab are used to prevent bleeding in hemophilia. In the cell-based model, they work mainly by:

Letting TF-VIIa keep making factor Xa

Replacing the missing factor VIII or IX

Bridging factors IXa and X like factor VIIIa

Blocking the breakdown of fibrin by plasmin

How does the cell-based model of coagulation differ from the classic cascade model?

It places clotting on tissue factor-bearing cells and platelets

It makes factor XII the main starter of clotting in the body

It was designed to explain the PT and APTT results

It treats the intrinsic and extrinsic pathways as separate routes

Prekallikrein and factor XI circulate bound to a cofactor that carries them to negatively charged surfaces during contact activation. That cofactor is:

High-molecular-weight kininogen

Coagulation cascade and its regulation

14 DOH Abu Dhabi (HAAD) lab licensing practice questions on Coagulation cascade and its regulation, part of Coagulation and Hemostasis. The first 14 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 26-year-old woman develops a proximal deep vein thrombosis 4 months after starting a combined oral contraceptive. Her mother had a pulmonary embolism during pregnancy. A sample taken before any heparin was given shows: antithrombin activity (factor Xa-based) 47% (reference 80-120%), antithrombin antigen 49% (80-120%), protein C activity 98% (70-140%), free protein S antigen 84% (60-130%), APC-resistance ratio 2.6 (normal above 2.0) and factor VIII 118% (50-150%). Over the next 2 days she needs unusually high doses of unfractionated heparin before her APTT reaches the therapeutic range. Which conclusion best explains both the thrombosis and the poor heparin response?
1. AAntithrombin lowered by heparin therapy
2. BHeparin resistance from a raised factor VIII
3. CType I (quantitative) antithrombin deficiency
4. DType II antithrombin deficiency (heparin-binding site)
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Answer: C · Type I (quantitative) antithrombin deficiency
Antithrombin activity and antigen are both reduced to about half, in proportion, which defines a type I (quantitative) deficiency; her mother's event fits autosomal dominant inheritance. Heparin works mainly by speeding up antithrombin's inactivation of thrombin and factor Xa, so with half the normal antithrombin much more heparin is needed to prolong the APTT. A type II defect, such as a heparin-binding-site variant, gives a low activity with a normal antigen. Heparin itself can lower antithrombin, but this sample was taken before heparin, and factor VIII, the usual cause of acute-phase heparin resistance, is normal. The deficiency should be confirmed on a repeat sample once the acute event and anticoagulation are over.
- A: The sample was taken before heparin, so heparin cannot have lowered it.
- B: Factor VIII is normal, so it cannot explain the heparin resistance.
- D: A type II defect has a normal antigen with a low activity; here both are low.
Question 2 · Easy
Which two activated factors are the main targets of antithrombin?
1. AThrombin and factor Xa
2. BFactors Va and VIIIa
3. CFactor VIIa and tissue factor
4. DFactor XIIIa and plasmin
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Answer: A · Thrombin and factor Xa
Antithrombin is a serine protease inhibitor (serpin) made in the liver. It forms a stable 1:1 complex with thrombin and factor Xa, and less effectively with IXa, XIa and XIIa. Heparin and endothelial heparan sulfate speed these reactions roughly a thousand-fold, which is the basis of heparin therapy.
- B: Va and VIIIa are inactivated by activated protein C.
- C: The TF-VIIa complex is shut down mainly by TFPI.
- D: Plasmin is inhibited mainly by alpha2-antiplasmin, and XIIIa is not an antithrombin target.
Question 3 · Hard
Anti-TFPI antibodies such as concizumab and marstacimab are used to prevent bleeding in hemophilia. In the cell-based model, they work mainly by:
1. AReplacing the missing factor VIII or IX
2. BBridging factors IXa and X like factor VIIIa
3. CLetting TF-VIIa keep making factor Xa
4. DBlocking the breakdown of fibrin by plasmin
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Answer: C · Letting TF-VIIa keep making factor Xa
TFPI normally shuts down the TF-VIIa complex once a little Xa has formed, so most of the Xa for the thrombin burst has to come from the IXa-VIIIa tenase on platelets. Blocking TFPI lets the TF-VIIa pathway keep producing Xa, which partly bypasses the missing factor VIII or IX. Because this does not need factor VIII or IX, it can also work when inhibitors are present.
- A: These antibodies contain no factor VIII or IX; they release the TFPI brake.
- B: Bridging IXa and X is how emicizumab works.
- D: Blocking fibrinolysis is how tranexamic acid works.
Question 4 · Medium
How does the cell-based model of coagulation differ from the classic cascade model?
1. AIt places clotting on tissue factor-bearing cells and platelets
2. BIt makes factor XII the main starter of clotting in the body
3. CIt was designed to explain the PT and APTT results
4. DIt treats the intrinsic and extrinsic pathways as separate routes
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Answer: A · It places clotting on tissue factor-bearing cells and platelets
The cell-based model describes overlapping phases on cell surfaces: initiation on tissue factor-bearing cells, amplification as thrombin activates platelets and cofactors, and propagation on the activated platelet surface. It explains why deficiencies of factors VIII, IX and XI cause bleeding although the tissue factor pathway is intact. The classic cascade, with separate intrinsic and extrinsic pathways, is still the best way to interpret PT and APTT results in plasma.
- B: Factor XII is not needed for hemostasis in the body; tissue factor starts clotting.
- C: Explaining the PT and APTT is what the classic cascade does well.
- D: Separate intrinsic and extrinsic pathways are the basis of the classic cascade.
Question 5 · Easy
Prekallikrein and factor XI circulate bound to a cofactor that carries them to negatively charged surfaces during contact activation. That cofactor is:
1. AVon Willebrand factor
2. BHigh-molecular-weight kininogen
3. CTissue factor
4. DThrombomodulin
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Answer: B · High-molecular-weight kininogen
High-molecular-weight kininogen (HMWK) forms complexes with prekallikrein and with factor XI and binds them to surfaces such as kaolin, silica or ellagic acid in the APTT. There, factor XIIa activates prekallikrein to kallikrein, which activates more factor XII, and XIIa also activates factor XI. Like factor XII and prekallikrein deficiency, HMWK deficiency prolongs the APTT without causing bleeding.
- A: VWF carries factor VIII, not the contact factors.
- C: Tissue factor is the cofactor for factor VIIa.
- D: Thrombomodulin is the endothelial cofactor that lets thrombin activate protein C.
Question 6 · Hard
In the cell-based model, factor IXa made on a tissue factor-bearing cell can diffuse to nearby platelets and help propagation, but factor Xa made there cannot. Why?
1. AFree Xa is quickly inhibited by TFPI and antithrombin
2. BIXa is shielded from inhibitors by factor VIIIa in plasma
3. CPlatelets carry no binding sites for factor Xa
4. DXa is too large a molecule to leave the cell surface
Answer and explanation in LearnFree account
Question 7 · Medium
About 60% of plasma protein S circulates bound to C4b-binding protein. What does this mean for its anticoagulant role?
1. AThe bound protein S inhibits factor Xa directly
2. BThe bound protein S activates protein C on endothelium
3. COnly the bound protein S acts as cofactor for APC
4. DOnly the free protein S acts as cofactor for APC
Answer and explanation in LearnFree account
Question 8 · Easy
Activated protein C, with protein S as its cofactor, inactivates factors:
1. AIIa and Xa
2. BVa and VIIIa
3. CVIIa and XIa
4. DIXa and Xa
Answer and explanation in LearnFree account
Question 9 · Hard
A 9-year-old with nephrotic syndrome (serum albumin 14 g/L [1.4 g/dL]) develops a renal vein thrombosis. Antithrombin activity is 45% (reference 80-120%), liver tests are normal and he has had no heparin. The most likely cause of the low antithrombin is:
1. ALoss of antithrombin in the urine
2. BReduced synthesis by the liver
3. CInherited type I antithrombin deficiency
4. DConsumption of antithrombin by heparin
Answer and explanation in LearnFree account
Question 10 · Medium
A raised plasma level of prothrombin fragment 1+2 is a marker of:
1. APlatelet granule release
2. BThrombin generation in vivo
3. CPlasmin generation in vivo
4. DFibrin cross-linking by XIIIa
Answer and explanation in LearnFree account
Question 11 · Easy
Which of these coagulation factors acts as a cofactor rather than as an enzyme?
1. AFactor IX
2. BFactor X
3. CFactor VIII
4. DFactor XIII
Answer and explanation in LearnFree account
Question 12 · Medium
The endothelial protein C receptor (EPCR) helps the protein C pathway by:
1. AReleasing protein S from C4b-binding protein
2. BActing as the cofactor for activated protein C
3. CCleaving factor Va directly on the endothelium
4. DPresenting protein C to thrombin-thrombomodulin
Answer and explanation in LearnFree account
Question 13 · Medium
The gamma-carboxyglutamic acid (Gla) residues of factors II, VII, IX and X are needed because they:
1. AForm the active serine site of the enzyme
2. BBind calcium and anchor the factor to phospholipid
3. CProtect the factor from antithrombin
4. DBind the factor to von Willebrand factor
Answer and explanation in LearnFree account
Question 14 · Easy
The flowchart shows a natural anticoagulant pathway with one step missing. Which reaction belongs in the dashed box?
Figure: MedExams
1. APlasminogen → plasmin
2. BFactor XIII → XIIIa
3. CProtein S → activated protein S
4. DProtein C → activated protein C
Answer and explanation in LearnFree account

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Coagulation cascade and its regulation

Which two activated factors are the main targets of antithrombin?

Anti-TFPI antibodies such as concizumab and marstacimab are used to prevent bleeding in hemophilia. In the cell-based model, they work mainly by:

How does the cell-based model of coagulation differ from the classic cascade model?

Prekallikrein and factor XI circulate bound to a cofactor that carries them to negatively charged surfaces during contact activation. That cofactor is:

In the cell-based model, factor IXa made on a tissue factor-bearing cell can diffuse to nearby platelets and help propagation, but factor Xa made there cannot. Why?

About 60% of plasma protein S circulates bound to C4b-binding protein. What does this mean for its anticoagulant role?

Activated protein C, with protein S as its cofactor, inactivates factors:

A 9-year-old with nephrotic syndrome (serum albumin 14 g/L [1.4 g/dL]) develops a renal vein thrombosis. Antithrombin activity is 45% (reference 80-120%), liver tests are normal and he has had no heparin. The most likely cause of the low antithrombin is:

A raised plasma level of prothrombin fragment 1+2 is a marker of:

Which of these coagulation factors acts as a cofactor rather than as an enzyme?

The endothelial protein C receptor (EPCR) helps the protein C pathway by:

The gamma-carboxyglutamic acid (Gla) residues of factors II, VII, IX and X are needed because they:

The flowchart shows a natural anticoagulant pathway with one step missing. Which reaction belongs in the dashed box?