Question 15

a)    State the reversal agent(s) for the following medications, and their indication(s).    (50% marks)

b)    List the mechanism of action for each stated reversal agent:

i.    Dabigatran (one specific agent)

ii.    Alteplase (tPA) (two specific agents)

iii.    Warfarin (two specific agents)
(50% marks)
 

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College answer

Not available.

Discussion

How would you structure your answer here, dear reader? It would seem that the question is asking two things about five agents. A table is probably the most natural manifestation of that sort of answer. To maximise the use of horizontal space, this sort of format is suggested:

Indications Mechanism of action
Idarucizumab for reversal of dabigatran

Life-threatening bleeding, eg. such that requires massive transfusion

Dabigatran is a direct thrombin inhibitor that acts by binding to thrombin.

Monoclonal antibody fragment binds dabigatran with 350 times more affinity than thrombin, thus neutralising its activity.  

Fibrinogen concentrate (eg. cryoprecipitate) for reversal of alteplase
Bleeding into vital organs, eg. intracranial, following thrombolysis

Alteplase produces fibrinolysis which degrades fibrin, depleting the reserves of fibrinogen

Cryoprecipitate replaces fibrinogen so that it can be used to reconstruct degraded fibrin in haemostatic thrombi.

Tranexamic acid for reversal of alteplase
Bleeding into vital organs, eg. intracranial, following thrombolysis

Alteplase is a recombinant tissue plasminogen activator, a serine protease that mediates fibrinolysis by activating plasminogen into plasmin. Tranexamic acid is a protease inhibitor that binds to lysine binding sites on plasminogen, preventing its cleavage by alteplase.

Vitamin K for reversal of warfarin
Excessive anticoagulation (INR >4) in patients without life-threatening haemorrhage

Warfarin prevents the synthesis of active Factors II, VII, IX, and X by inhibiting the activity of vitamin K epoxide reductase complex.

Vitamin K replacement corrects the deficit of reduced vitamin K, allowing normal synthesis of clotting factors to resume

Prothrombin concentrate for reversal of warfarin
Lifethreatening bleeding or other need for immediate reversal of warfarin anticoagulation Prothrombinex is a lyophilized concentrate of human Factors IX, II and X, which reverses the factor deficiency that results from warfarin.