Editorial <\/p>\n\n\n\n
Cardiac surgery is the largest consumer of blood and blood derivatives in all surgical specialties, and it accounts for 15% of the nation\u2019s allocated blood.1<\/a><\/sup> This creates pressure on hospital resources and blood availability to meet transfusion requirements. In addition, there have been persistent efforts through national societies to implement strict processes for blood transfusion in cardiac surgery to improve patient clinical outcomes.2<\/a><\/sup><\/a><\/p>\n\n\n\n Treatment of coagulopathic bleeding is often a \u201ckitchen-sink\u201d approach of indiscriminate administration of blood products that has changed little over the years. When coagulation factor deficiency is the cause for perioperative bleeding, historically frozen plasma transfusion has been most commonly used to replenish thrombin-generating coagulation factors and restore the coagulation system. Transfusion-related acute lung injury and infectious complications are only a few of the well-known adverse effects of frozen plasma transfusion. Additionally, the recommended dose for frozen plasma is 10 to 15 mL\/kg body weight, which for a 70-kg person is approximately 4 units. This has important downstream effects in the cardiac surgery patient and may precipitate transfusion-associated circulatory overload. Patients with tenuous clinical status and significant right ventricular dysfunction are at particular risk for volume overload. Transfusing a large amount of frozen plasma ultimately leads to dilution of other important components of blood, such as platelets and red blood cells, and may paradoxically increase overall transfused volume of blood products.<\/a><\/p>\n\n\n\n Recently, 4-factor prothrombin complex concentrate (PCC) has emerged as an attractive alternative to frozen plasma in the management of perioperative bleeding,3<\/a><\/sup> because of its low volume, pathogen reduction, absence of compatibility concerns, no need of thawing, and ease of administration. For centers where frozen plasma needs to be thawed, it is time-efficient to administer PCC, which requires 15 minutes of reconstitution time.<\/a><\/p>\n\n\n\n PCC use has lagged compared with frozen plasma, and in a large, randomized trial investigating restrictive vs liberal transfusion strategies in cardiac surgery, frozen plasma was 8 to 10 times more likely to be administered than PCC.4<\/a><\/sup> Unfamiliarity with PCC, paucity of data from large trials, concerns about thromboembolic risks in the acute surgical setting, and direct cost have been major barriers to its adoption into clinical practice. In the surgical setting, PCC has been approved by the US Food and Drug Administration for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist therapy in patients who need urgent surgery or invasive procedure. However, several small studies have shown that PCC was effective at reducing transfusions in cardiac operations without an increased thrombotic risk compared with frozen plasma and have encouraged more liberal use of PCC. Earlier this year, a consensus statement by the Enhanced Recovery After Cardiac Surgery Society and Society for the Advancement of Patient Blood Management called for further confirmation of the safety profile of PCC in multicenter randomized trials.3<\/a><\/sup><\/a><\/p>\n\n\n\n Just published in JAMA<\/em>, the Factor Replacement in Surgery II (FARES-II) randomized clinical trial, which compared the effectiveness and safety of PCC vs frozen plasma, may have answered this call.5<\/a><\/sup> In the trial conducted at 10 Canadian and 2 US centers, eligible patients were randomized to receive PCC or frozen plasma. The primary analysis of 420 patients compared hemostatic response (a composite outcome defined as no hemostatic interventions, such as transfusions and surgical reexplorations, in the first 24 hours after treatment initiation) between patients who received PCC at a dose of 1500 IU (<60 kg body weight) or 2000 IU (>60 kg) vs frozen plasma, 3 units (<60 kg body weight) or 4 units (>60 kg). Compared with the 207 patients in the frozen plasma group, the 213 patients in the PCC group had higher hemostatic effectiveness (166 [77.9%] vs 125 [60.4%]; difference, 17.6%; 95%CI, 8.7%-26.4%), satisfying the noninferiority and superiority testing. Secondary outcomes, including blood product transfusions and chest tube output, were also reduced in the PCC group. With regard to safety, the PCC group had lower rates of serious adverse events, including acute kidney injury. FARES-II overcomes the deficiencies of previously published studies, in which PCC was administered at a dose of 15 IU\/kg, lower than the largely accepted 25 IU\/kg.<\/a><\/p>\n\n\n\n The 2021 update to the clinical practice guidelines on patient blood management assigns PCC a class IIa (reasonable to choose) over frozen plasma as first-line therapy for refractory coagulopathy in cardiac surgery in select situations to reduce bleeding.2<\/a><\/sup> So, has the time come to make PCC the standard of care (class I recommendation), retire the use of frozen plasma, and make a phone call to the pharmacy instead of the blood bank?<\/a><\/p>\n\n\n\n Here are some important limitations to consider: FARES-II was unblinded and the design resulted in 20% dropout of patients who did not need factor replacement or declined consent. Although the percentage of dropout was anticipated and almost balanced between groups, there were notable differences in variables that influence bleeding risk. Patients who received frozen plasma had higher prevalence of chronic lung disease (17.4% vs 11.7% for the PCC group), endocarditis (7.3% vs 3.8%), reoperations (27.1% vs 24.9%), nonelective surgery (21.3 vs 16.9%), and complex surgery (73.4% vs 67.6%) and had longer cardiopulmonary bypass times (176 vs 171 minutes), all of which are known risk factors for bleeding. Although data from large national registries associate blood transfusions with major morbidity and mortality in cardiac surgery,6<\/a><\/sup>,7<\/a><\/sup> the reduced blood transfusion rate in the PCC group did not translate into a survival benefit. There was no difference in the durations of mechanical ventilation and hospital stay. Additionally, given the high cost of PCC, the financial feasibility has not been assessed.<\/a><\/p>\n\n\n\n It is important to be careful in cases that require temporary mechanical circulatory support because of the risk of circuit and prosthetic valve thrombosis. The FARES-II trial excluded heart failure surgery such as heart transplantation or insertion of ventricular assist devices, where this vulnerable group of cardiac surgery patients may benefit the most from the low volume of factor concentrate, especially in the setting of significant right ventricular dysfunction. Conversely, the atria and ventricles may act as a reservoir of concentrated coagulation factors in the failing heart and precipitate intracardiac thrombosis, a devastating and often lethal complication. Lastly, it is unknown whether PCC would be safe in the setting of pathologically activated coagulation and factor consumption, such as aortic dissections, infectious endocarditis, and other acute or subacute inflammatory processes.<\/a><\/p>\n\n\n\n FARES-II provides several important takeaways. It demonstrates that PCC offers superior hemostatic efficacy and safety advantage over traditional frozen plasma for treatment of coagulation factor deficiency\u2013induced bleeding in cardiac surgery. The new evidence is important not only for the benefit of the individual patient, but also to reduce stress on hospital blood supply. What remains unknown is the safety of PCC in patients with severe systolic dysfunction and patients receiving mechanical circulatory support. Further research is required to determine the impact of PCC on major clinical outcomes and economic consequences for health care systems. Until we have these answers, we may not choose between the pharmacy and blood bank; we should use both.<\/p>\n","protected":false},"excerpt":{"rendered":" Editorial Coagulopathy Treatment in Cardiac Surge […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28609"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=28609"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28609\/revisions"}],"predecessor-version":[{"id":28610,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28609\/revisions\/28610"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=28609"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=28609"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=28609"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}