13. ANTICOAGULATION

13.1 Background
LT-MCS devices require antithrombotic therapy due to the presence of the artificial surfaces of the pump and the modified fluid dynamic pattern of the blood accompanied by shear forces. Anticoagulation for LT-MCS comprises 3 different periods: preoperative, intraoperative and early postoperative. Management is often similar to that of other cardiac surgery procedures [64]; however, some situations require specific considerations as outlined below. Each phase has distinct issues and requires specific management. Long-term antithrombotic therapy is more standardized, although patients may tread a fine line between bleeding and thrombosis. Furthermore, the optimal long-term regimen of anticoagulation should be tailored to the recipient and the device type. In this context, the development of clinical analysis tools and/or risk scores is encouraged.

13.2 Description of evidence

Preoperative conditions
Normalization of coagulation before LT-MCS implantation is crucial to avoid the postoperative cascade of bleeding, transfusions and volume overload, RV failure and surgical re-exploration. Preoperative temporary MCS, in particular, requires an antithrombotic regimen with intravenous drugs. Coagulopathy is inevitably present due to activation and consumption of coagulation factors secondary to cardiogenic shock and exposure to biomaterials and devices. This condition requires specific and more aggressive preoperative treatment.

Intraoperative conditions
Intraoperative full anticoagulation is recommended and, in line with other cardiac surgery protocols, with full reversal and restoration of blood components and coagulation factors at the end [64], except for off-pump surgical techniques or implant of extracorporeal life support, where a lower dose of heparin may be considered.

Postoperative conditions
Postoperative early anticoagulation is mandatory to prevent thrombotic events. Intravenous administration is the primary choice: unfractionated heparin is commonly used, but successful use of direct thrombin inhibitors has been reported. Anticoagulation can be commenced 8 h after surgery with all devices if bleeding is <50 ml/h [338]. Initially, the target activated partial thromboplastin time is 40 s; it is progressively increased to 55–60 s within the first 48–72 h postoperatively. Oral anticoagulation with the vitamin K antagonist should be initiated once the clinical condition is considered stable and oral intake is possible. The international normalized ratio (INR) target is set according to device recommendations for modern LT-MCS devices. The INR target is between 2.0 and 3.0. Acetylsalicylic acid is routinely administered according to device specifications. The use of new oral anticoagulants is currently not recommended.
Measurement of both the activated partial thromboplastin time and factor Xa are recommended for monitoring anticoagulation therapy. Bridging with intravenous heparin is recommended if the INR is <2.0 and in cases of planned invasive procedures or non-cardiac surgical procedures for perioperative bridging. Low-molecular-weight heparin may be considered as well.
Frequent INR checks using home INR monitoring and dedicated staff (for instance, trained pharmacists) permit strict anticoagulation management [339, 340]. Intravenous direct thrombin inhibitors such as bivalirudin and argatroban should be used as alternative anticoagulation agents for patients with heparin-induced thrombocytopenia.
Antithrombotic therapy should be patient-tailored during the time on support and in the different clinical situations. Technical equipment necessary for in-depth analysis is not yet available for point-of-care testing [341], thus preventing a more detailed approach in routine clinical practice.