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)
Not available.
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. |
Pollack Jr, Charles V., et al. "Idarucizumab for dabigatran reversal." New England Journal of Medicine 373.6 (2015): 511-520.
Yaghi, Shadi, et al. "Treatment and outcome of hemorrhagic transformation after intravenous alteplase in acute ischemic stroke: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association." Stroke 48.12 (2017): e343-e361.
Tran, Huyen A., et al. "An update of consensus guidelines for warfarin reversal."Med J Aust 198 (2013): 198-9.