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Surgical patients, following procedural interventions or traumatic injury, often bleed due to ongoing blood loss or coagulopathy. Volume resuscitation and transfusion management are critical for the massively bleeding patient. While transfusions may correct coagulopathy, they carry multiple risks including circulatory overload and transfusion-related acute lung injury. Factor concentrates, specifically prothrombin complex concentrates (PCCs), are often used as part of multimodal therapy for bleeding along with laboratory testing to rapidly assess underlying coagulopathy. Although they are commonly used as part of management algorithms, studies evaluating their efficacy against fresh frozen plasma (FFP) or other potential therapies are needed. Further, PCCs are indicated to treat the coagulopathy associated with non-vitamin K oral anticoagulants in the perioperative setting. The focus of this commentary will be the perioperative use of PCCs, plasma, and FFP., Competing Interests: J.H.L. serves on research steering committees or advisory boards for Boehringer-Ingelheim, CSL Behring, Instrumentation Laboratories, Octapharma, and Merck. K.G. receives support from NIGMS T32GM008600 and Duke Health. N.H.W. receives grants for clinical research from Allergan, is supported by AHA Grant 16MCPRP30700010, and the NIGMS T32 postdoctoral training grant T32GM008600, and serves as a consultant to Allergan. J.M.C. reports grants from CSL Behring, personal fees from Portola and Brisol-Meyrs Squibb, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background/objectives: Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications., Materials/methods: After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine ® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing., Results: Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%., Conclusions: 3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications., (© 2019 International Society of Blood Transfusion.)

Patients who are critically ill following surgical or traumatic injury often present with coagulopathy as a component of the complex multisystem dysfunction that clinicians must rapidly diagnose and treat in the intensive care environment. Failure to recognize coagulopathy while volume resuscitation with crystalloid or colloid takes place, or an unbalanced transfusion strategy focused on packed red blood cell transfusion can all significantly worsen coagulopathy, leading to increased transfusion requirements and poor outcomes. Even an optimized transfusion strategy directed at correcting coagulopathy and maintaining clotting factor levels carries the risk of a number of transfusion reactions including transfusion-related acute lung injury, transfusion-related circulatory overload, anaphylaxis, and septic shock. A number of adjunctive strategies can be used either to augment a balanced transfusion approach or as alternatives to blood component therapy. Coupled with an appropriate and timely laboratory testing, this approach can quickly diagnose a patient's specific coagulopathy and work to correct it as quickly as possible, minimizing the requirement of blood transfusion and the pathophysiologic effects of excessive bleeding and fibrinolysis. We will review the literature supporting this approach and provide insight into how these approaches can be best used to care for bleeding patients in the intensive care unit. Finally, the increasing use of several novel oral anticoagulants, novel antiplatelet drugs, and low-molecular weight heparin to clinical practice has complicated the care of the coagulopathic patient when these drugs are involved. Many clinicians familiar with heparin and warfarin reversal are not familiar with the optimal way to reverse the action of these new drugs. Patients treated with these drugs for a wide variety of conditions including atrial fibrillation, stroke, coronary artery stent, deep venous thrombosis, and pulmonary embolism will present for emergency surgery and will require management of pharmacologically induced postoperative coagulopathy. We will discuss optimized strategies for reversal of these agents and strategies that are currently under development., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.