Fibrinolysis

6 DOH Abu Dhabi (HAAD) lab licensing practice questions on Fibrinolysis, part of Coagulation and Hemostasis. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Medium

   A 15-year-old with type 1 von Willebrand disease is given tranexamic acid before a dental extraction. How does the drug reduce bleeding?

   1. AIt activates platelet GPIIb/IIIa receptors
   2. BIt blocks the lysine-binding sites of plasminogen
   3. CIt speeds up cross-linking by factor XIIIa
   4. DIt inhibits thrombin and factor Xa directly

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   Answer: B · It blocks the lysine-binding sites of plasminogen

   Tranexamic acid is a synthetic lysine analogue. It occupies the lysine-binding sites of plasminogen, so plasminogen cannot bind to fibrin and be activated there by tPA, and clots last longer. It is especially useful in the mouth and in heavy menstrual bleeding, where local fibrinolytic activity is high.

   • A: It has no direct effect on platelet receptors.
   • C: Tranexamic acid does not act on factor XIII.
   • D: Direct thrombin and Xa inhibitors are anticoagulants, the opposite effect.

2. Question 2 · Easy

   Which protein is the main inhibitor of free plasmin in the circulation?

   1. AAlpha2-antiplasmin
   2. BPlasminogen activator inhibitor-1
   3. CAlpha1-antitrypsin
   4. DAntithrombin

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   Answer: A · Alpha2-antiplasmin

   Alpha2-antiplasmin, made in the liver, inactivates free plasmin very rapidly, so plasmin cannot digest circulating fibrinogen and factors V and VIII. Factor XIIIa also cross-links some alpha2-antiplasmin into the clot, which protects fibrin from early lysis. Plasmin bound to fibrin is partly shielded from the inhibitor, so lysis goes on where it is needed.

   • B: PAI-1 inhibits the plasminogen activators tPA and urokinase, not plasmin itself.
   • C: Alpha1-antitrypsin mainly inhibits neutrophil elastase.
   • D: Antithrombin mainly inhibits thrombin and factor Xa.

3. Question 3 · Hard

   Plasma from a patient with severe factor XIII deficiency (activity below 1%) is clotted in the laboratory, and the clot is then digested with plasmin. Compared with a clot from normal plasma, the digest contains:

   1. ALittle D-dimer, since the fibrin was not cross-linked
   2. BThe same D-dimer, since plasmin alone forms it
   3. CMore D-dimer, since the clot dissolves faster
   4. DNo fragments, since plasmin cannot cleave it

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   Answer: A · Little D-dimer, since the fibrin was not cross-linked

   D-dimer is two D domains from neighbouring fibrin molecules held together by the covalent bond that factor XIIIa forms. Without factor XIIIa, plasmin cuts the fibrin into separate D and E fragments, so a D-dimer assay finds little. The non-cross-linked clot is also weaker and lyses more easily, one reason why factor XIII deficiency causes delayed bleeding.

   • B: Plasmin releases D-dimer only from fibrin that factor XIIIa has cross-linked.
   • C: Faster lysis gives more fragments, but they are D monomers, not D-dimer.
   • D: Plasmin digests non-cross-linked fibrin readily.

4. Question 4 · Medium

   Thrombin-activatable fibrinolysis inhibitor (TAFI), activated by thrombin bound to thrombomodulin, slows clot lysis by:

   1. ARemoving C-terminal lysines from partly digested fibrin
   2. BCross-linking alpha2-antiplasmin into fibrin
   3. CInactivating tissue plasminogen activator directly
   4. DInhibiting free plasmin in the circulation

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   Answer: A · Removing C-terminal lysines from partly digested fibrin

   Activated TAFI is a carboxypeptidase. As plasmin digests fibrin it exposes C-terminal lysines that bind more plasminogen and tPA and speed lysis; TAFIa removes them and breaks this positive feedback. Thrombin bound to thrombomodulin activates TAFI far better than free thrombin, so the amount of thrombin generated also decides how long the clot lasts.

   • B: Cross-linking alpha2-antiplasmin into fibrin is done by factor XIIIa.
   • C: Direct inactivation of tPA is the action of PAI-1.
   • D: Free plasmin is inhibited by alpha2-antiplasmin.

5. Question 5 · Easy

   When plasmin digests fibrinogen that has not been cross-linked, its final breakdown products are:

   1. AFibrinopeptides A and B
   2. BD-dimer and fragment E
   3. CFragments D and E
   4. DFibrin monomers

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   Answer: C · Fragments D and E

   Plasmin first cuts fibrinogen into fragment X, then into fragments Y and D, and finally into two D fragments and one E fragment. These degradation products form whether plasmin acts on fibrinogen or on fibrin that is not cross-linked. D-dimer appears only when factor XIIIa has joined the D domains of neighbouring fibrin molecules, so it shows that a stabilized clot has formed and been lysed.

   • A: Fibrinopeptides are split off by thrombin, not plasmin.
   • B: D-dimer needs fibrin that factor XIIIa has cross-linked.
   • D: Fibrin monomers are made by thrombin and then polymerize; they are not plasmin products.

6. Question 6 · Medium

   Plasminogen activator inhibitor-1 (PAI-1) is raised in obesity, metabolic syndrome and inflammation. Why do high levels favor thrombosis?

   1. AIt blocks endothelial thrombomodulin
   2. BIt inactivates alpha2-antiplasmin
   3. CIt inactivates tPA and urokinase
   4. DIt speeds up factor Xa formation

   Answer and explanation in LearnFree account