24th July 2024

Anticoagulants and antiplatelets

MRCP Part 2 will not test your ability to recall the exact mechanisms as described in the diagram above, however they may test the clinical application, for example how common anticoagulants affect the clotting cascade.

Warfarin

• Mechanism: inhibits the vitamin K-dependent synthesis of clotting factors II, VII, IX and X
• Monitoring: INR (derived from PT)
• Key indications: prosthetic heart valves requiring anticoagulation; AF and VTE, although DOACs (see below) are increasingly being used for these conditions
• Takes around five days to reach therapeutic effect, and for the first 36 hours is pro-thrombotic due to  decreased protein C and S. Bridging therapy with other anticoagulants may be necessary
• Caution with medications affecting the cytochrome P450 system (Table 2), which metabolises warfarin. Inducers decrease the concentration of warfarin, thus lowering the INR. Inhibitors of the cytochrome P450 system increase the concentration of warfarin

• Side effects: can include pain and purpura in digits
• Reversal: prothrombin complex concentrate (acts within minutes) and vitamin K (slower)
• Deficiency in vitamin K can mimic effects of taking warfarin with prolonged PT and INR. This can occur in conditions such as malnutrition or malabsorption (terminal ileal resection)

Direct oral anticoagulants (DOAC)

• Mechanism: factor Xa inhibition (rivaroxaban, edoxaban, apixaban) or thrombin inhibition (dabigatran)
• Key indications: non-valvular AF and VTE
• Reversal: andexanet alfa (apixaban and rivaroxaban); idarucizumab (dabigatran)
• Benefits: no need for regular monitoring

Heparin

• Unfractionated heparin (UFH): binds to antithrombin, enhancing inhibition of multiple factors, predominantly thrombin and Xa. Monitoring is with APTT. Benefits include that it can be given in renal failure and that it can be stopped rapidly by stopping the infusion
• Low molecular weight heparin (LMWH): binds to antithrombin, predominantly resulting in increased inhibition of factor Xa (less inhibition of thrombin than with UFH). Monitoring is with factor Xa activity assays. Benefits include that there is no need for IV administration (given subcutaneously) or monitoring
• Indication: VTE prophylaxis or treatment; used in procedures, e.g. angiography
• Reversal: protamine
• Heparin-induced thrombocytopenia is a complication of heparin use
• Special circumstances: heparin may be chosen as long-term anticoagulation in cancer patients who have evidence of liver impairment such as those with liver metastases. In pregnancy, heparin is the anticoagulation of choice

Antiplatelets

It is also worth noting the mechanism of key antiplatelet drugs. These are used predominantly for arterial disease such as in myocardial infarction and acute strokes (anticoagulation may be started after a delay if indicated, e.g. in AF, but antiplatelets are the initial mainstay to reduce the risk of haemorrhagic transformation).

Periprocedural antithrombotic medication management

Prior to invasive procedures it is important to review a patient’s drug chart. Antiplatelets and anticoagulation may need to be held before proceeding. The decision to withhold will be a weighing up of risk versus benefit.

Find below a short summary of British Society of Gastroenterology guidelines. Classify procedures as high risk (e.g. ERCP, therapy for varices) or low risk (e.g. diagnostic procedures ± biopsy), and patients as having high thrombotic risk (e.g. recent coronary stent) or low (e.g. ischaemic heart disease but no stents).

• Clopidogrel, prasugrel: for low-risk procedures, continue. For high-risk procedures and low thrombotic risk, discontinue 5 days prior. For high-risk procedures and high thrombotic risk, liaise with a cardiologist
• DOACs: for low-risk procedures omit morning dose. For high risk-procedures hold DOAC for 48 hours
• Warfarin: for low-risk procedures, if INR is within range, continue; if INR is raised, delay until within range. For high-risk procedures and low thrombotic risk (e.g. prosthetic aortic valve), stop warfarin for a week and proceed when INR <1.5, then restart warfarin on the evening of the procedure. For high-risk procedures and high thrombotic risk (e.g. prosthetic mitral valve), omit warfarin for 5 days and cover with LMWH for 48 h prior. Restart warfarin on the evening of procedure

For lumbar punctures, aspirin can be continued, however clopidogrel is commonly held 7 days prior to procedure.

The above provides a rough guide and should be used as a framework which can be applied to other procedures such as intercostal drains. Prior to surgery, a discussion is warranted between surgical and haematology teams.  Please refer to society or local hospital guidelines where applicable for up-to-date guidance.