Antifibrinolytics
Both aprotinin and tranexamic acid are antifibrinolytic agents that have been used widely in this setting to reduce blood loss.
Aprotinin
This agent is currently suspended from marketing.
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Aprotinin is a non-specific serine protease inhibitor (inhibits plasmin at low dose, kallikrein at high dose, activated protein c and thrombin), which, in addition to its anti-fibrinolytic properties, may have effects on promoting platelet function by blocking the thrombin activated protease-activated receptor 1 (PAR1), and appears to affect novel anti-inflammatory targets preventing transmigration of leucocytes.
Efficacy is dose dependent over a wide range of surgery, and in cardiac surgery the high dose regime reduces blood requirements and perioperative bleeding by two-thirds. As aprotonin is derived from bovine lung there is a risk of allergy especially with repeated doses, therefore a test dose should always be performed.
Tranexamic acid
This is a synthetically derived antifibrinolytic agent that has its effects by the prevention of the interaction between plasminogen with fibrin via interaction with lysine receptors. It is has been shown to be safe, reduces blood loss but not transfusion and is cheaper than aprotinin.
Tranexamic acid is not licensed for the prophylaxis or treatment of bleeding following cardiac surgery in the UK. It is licensed for the prophylaxis and treatment of local fibrinolysis in patients at high risk of haemorrhage following prostatectomy, conisation of the cervix, and surgical procedures or dental extractions in haemophiliac patients. It is also licensed in the management of general fibrinolysis associated with thrombolytic therapy and haemorrhage associated with disseminated intravascular coagulation with predominant activation of the fibrinolytic system.
DDAVP
Is an analogue of vasopressin. It can increase Factor VIII by increasing von Willebrand factor from the epithelium It is used routinely in mild haemophilia and von Willebrands disease, some platelet disorders and occasionally in cardiac surgery to enhance platelet function.
Fibrin Sealants
Fibrin sealants mimic the final stages of the clotting cascade, however their action is independent of the body's normal clotting mechanism. The use of fibrin sealants is primarly to achieve inter-operative haemostasis but they can also be used to seal air, bile and lymphatic leaks and also suture holes in an anastomosis.
As commercially available fibrin sealants are manufactured from fibrinogen and thrombin derived from human plasma, patient details should be kept to enable look back . An anti fibrinolytic agent, which is either tranexamic acid or bovine aprotinin, is used in the products to increase the lifespan of the clot by inhibiting fibrinolysis.
There are currently 3 fibrin sealants commercially available in Europe - Quixil, Tisseal and Beriplast.
The article 'Evaluating the differences between fibrin sealants: recommendations from an international advisory panel of hospital pharmacists' (EJHP Science. Vol 12.2006;1:3-9) contains a table (page 4) comparing the composition of commercial fibrin sealants. The article can be downloaded as a pdf from www.eahp.eu/EJHP/EJHP-Science.
As a result of the different composition of the fibrin sealants, Tisseal and Beriplast are contraindicated for patients who have hypersentivity to bovine aprotinin. Quixil is contraindicated in surgical procedures in which there may be contact with the dura mater or cerebral spinal fluid as studies have shown that tranexamic acid can induce neurotoxicity.