*Heparinoids*

Danaparoid is produced from the same porcine material as heparin, but all heparin and heparin fragments are extracted. It catalyses AT-mediated inhibition of FXa and, to a lesser extent, FIIa (17). It has been used to anticoagulate patients with HIT. There can be crossreactivity so patients should continue to have platelet count monitored (18). Coagulation monitoring, if required, is by anti-Xa assay. It is not reversed by protamine.

#### *Warfarin*

This oral agent is used to minimise the risk of embolic stroke in patients with valvular heart disease or arrhythmia, and to prevent/treat venous thromboembolism. It inhibits the hepatic synthesis of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) as well as proteins C, S and Z (19). It takes at least 48hrs to develop the anticoagulant effect, during which time the inhibition of proteins C and S may paradoxically create a prothrombotic state, hence heparin is usually added during warfarin introduction. Warfarin effect is titrated using PT or INR tests with target ranges shown in the table. Additional or alternative agents may be recommended in valvular or structural heart disease (20).

Perioperatively, warfarin is only continued for certain procedures with low risk of bleeding. Warfarin is usually held 5 days prior to surgery with INR ≤1.5 confirmed immediately preop. A shorter-acting anticoagulant, such as LMWH, can be given as bridging anticoagulant therapy until shortly before surgery and continued once haemostasis has been obtained. The decreased risk of thrombosis or embolism by using bridging anticoagulation is weighed against the increased risk of haemorrhage. Decisions regarding perioperative anticoagulation are made on an individual patient basis (22).


INR = International Normalised Ratio, DVT = Deep Venous Thrombosis, PE = Pulmonary Embolism (22) Fig. 5. INR targets.

In the event of major haemorrhage in a patient who is anticoagulated with warfarin, it may be necessary to discontinue warfarin, administer vitamin K 5-10mg (phytomenadione), and in some cases replace the deficient coagulation factors using prothrombin complex concentrate 30-50 units/kg (containing FII, FVII, FIX, FX) or fresh frozen plasma 10- 15ml/kg.

### *Antiplatelet agents*

188 Perioperative Considerations in Cardiac Surgery

Fondaparinux. It does not affect PT, APTT or ACT. Although monitoring is not routinely

Newer orally-administered drugs Rivaroxiban and Apixaban are direct FXa inhibitors. They

Danaparoid is produced from the same porcine material as heparin, but all heparin and heparin fragments are extracted. It catalyses AT-mediated inhibition of FXa and, to a lesser extent, FIIa (17). It has been used to anticoagulate patients with HIT. There can be crossreactivity so patients should continue to have platelet count monitored (18). Coagulation

This oral agent is used to minimise the risk of embolic stroke in patients with valvular heart disease or arrhythmia, and to prevent/treat venous thromboembolism. It inhibits the hepatic synthesis of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) as well as proteins C, S and Z (19). It takes at least 48hrs to develop the anticoagulant effect, during which time the inhibition of proteins C and S may paradoxically create a prothrombotic state, hence heparin is usually added during warfarin introduction. Warfarin effect is titrated using PT or INR tests with target ranges shown in the table. Additional or

Perioperatively, warfarin is only continued for certain procedures with low risk of bleeding. Warfarin is usually held 5 days prior to surgery with INR ≤1.5 confirmed immediately preop. A shorter-acting anticoagulant, such as LMWH, can be given as bridging anticoagulant therapy until shortly before surgery and continued once haemostasis has been obtained. The decreased risk of thrombosis or embolism by using bridging anticoagulation is weighed against the increased risk of haemorrhage. Decisions regarding perioperative

**Warfarin Indication Target INR (+/- 0.5)** 

≥ 4 weeks post-Cardioversion

Typically 3 for aortic valves,

discontinuation if no other risk

3.5 for mitral valves.

after which consider

factors

For Cardioversion in Atrial Fibrillation 3.0 for ≥ 3 weeks prior, and 2.5 for

Bioprosthetic Valves 2.5 for 3 months post-insertion,

INR = International Normalised Ratio, DVT = Deep Venous Thrombosis, PE = Pulmonary Embolism (22)

alternative agents may be recommended in valvular or structural heart disease (20).

anticoagulation are made on an individual patient basis (22).

Atrial fibrillation, DVT, PE 2.5 Recurrent DVT/PE despite INR >2 3.5

Individualised targets based on: (a) thrombogenic risk of the valve type and position, (b) patientrelated risk factors for thrombosis and haemorrhage

Mechanical Prosthetic Heart Valves:

(20, 21).

Fig. 5. INR targets.

required in healthy patients, it can be achieved by an anti-FXa assay.

monitoring, if required, is by anti-Xa assay. It is not reversed by protamine.

have similar indications to Fondaparinux.

*Heparinoids* 

*Warfarin* 

These agents have a variety of mechanisms of action as shown in the table. Decisions regarding perioperative discontinuation of these medications are made on an individual patient basis. As with other anticoagulants, continuation increases perioperative bleeding but withholding the agent increases risk of thrombosis. The risk of withholding antiplatelet agents in the setting of acute coronary syndrome generally outweighs the benefits so they are usually continued in this context (23).

#### *Prostacyclins*

Epoprostenol is a prostacyclin that can be infused to treat pulmonary hypertension, or to inhibit platelet aggregation during renal dialysis.

#### *Antifibrinolytic Agents*

Aprotinin, tranexamic acid and aminocaproic acid are antifibrinolytic agents, which can be used to decrease peri-operative bleeding. Aprotinin is a naturally-occurring serine protease inhibitor, and the other two agents are lysine analogues. Studies have shown reduction in blood loss and transfusion requirements with the use of these agents, particularly in patients taking antiplatelet agents perioperatively (25, 26).

Aprotinin was associated with increased incidence of death, cerebrovascular accidents and renal events in an observational study of patients undergoing revascularisation surgery (27). These effects were not seen with tranexamic acid or ε aminocaproic acid. Indeed a prior meta-analysis of aprotinin use in patients undergoing cardiopulmonary bypass suggested it was safe (28). The current recommendation is to reserve aprotinin use for patients at the highest risk of bleeding complications (29).
