A European consensus statement on the use of four‐factor prothrombin complex concentrate for cardiac and non‐cardiac surgical patients

Abstract

Summary Modern four‐factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist‐related bleeding vary greatly. They include INR and bodyweight‐related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four‐factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four‐factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four‐factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg‐1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half‐dose bolus (12.5 IU.kg‐1) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue‐factor‐activated, factor VII‐dependent and heparin insensitive point‐of‐care tests may be used for peri‐operative monitoring and guiding of prothrombin complex concentrate therapy.

Management of Coagulopathy in Bleeding Patients

“…Furthermore, in emergency situations the administration of specific reversal agents can be delayed if the type and plasma level of DOAC present in a patient’s blood needs to be rapidly identified with specific tests [ 58 , 59 ]. Non-specific strategies for the treatment of DOAC-associated bleeding, such as administration of PCC, are now widely recognised and recommended by different organisations for situations when specific agents are not readily available [ 12 , 14 , 41 , 42 , 47 , 48 , 50 , 51 , 52 , 54 , 60 ]. The guideline recommendations are summarised in Table 1 .…”

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care

“…Prothrombin Complex Concentrate PCC contains the vitamin K-dependent factors II, VII, IX, and X (4-factor PCC) or II, IX, and X (3-factor PCC). Following the initial approval for hemophilia B, the vial is standardized on factor IX; the content of the other coagulation factors can vary significantly among the different preparations [75]. The concentration of clotting factors is approximately 25-fold that of plasma [15,29].…”

“…As the clotting times of VET are not sensitive to reduced anticoagulant levels (e.g., antithrombin), their use as a surrogate remains debatable [80]. For coagulopathic, severe bleeding, an initial bolus of 25 IU/kg BW appears to be effective and for those patients with an increased risk for thromboembolism an initial half-dose bolus of 12.5 IU/kg BW followed by a second dose if microvascular bleeding persists [75]. In an evidence-based algorithm for ROTEM-guided bleeding management, PCC substitution is indicated with an EXTEM CT >80 s and FIBTEM A5 ≥9 mm (trauma) or ≥12 mm (PPH) [48].…”

Reversal Agents for the Management of Direct Oral Anticoagulant-Related Bleeding in Cardiac Surgical Patients: The Emperor's New Clothes?

“…For the patient taking warfarin, prothrombin complex concentrate is recommended in accordance with recently published guidelines. 3,4 For patients taking dabigatran, it is recommended that idarucrizumab is given. For patients taking apixaban, rivaroxaban, betrixaban or edoxaban, andexanet alpha is recommended, albeit off-label for those taking betrixaban and edoxaban.…”