It catalyzes the conversion of fibrinogen to fibrin and also activates platelets through protease-activated receptors (PARs) 1 and 4 on platelet surfaces. Retrospective study of rFVIIa, 4-factor PCC, and a rFVIIa and 3-factor PCC combination in improving bleeding outcomes in the warfarin and non-warfarin patient. Accepted for publication February 8, 2021. Prothrombin complex concentrate doses received before CPB end, such as for warfarin reversal, were not included in the analysis (n = 25). Li JY, Gong J, Zhu F, et al. Prothrombin complex concentrate ( PCC ), also known as factor IX complex, is a medication made up of blood clotting factors II, IX, and X. Updated information for blood establishments regarding the COVID-19 pandemic and blood donation. 2011; 113:13191333. Fibrinogen or cryoprecipitate - Targeting a slightly higher level than usual might be helpful, but evidence on this is scant. Direct oral anticoagulation agents have a different mechanism of action: apixaban and rivaroxabanare inhibitors of factor Xa, and dabigatran inhibits thrombin. <> Use of Prothrombin Complex Concentrate (Beriplex/Octaplex) in Acquired Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Prothrombincomplex concentrates (PCCs) are highly purified concentrates with haemostatic activity pre- paredfrom pooled plasma. PDF Cryo Preci Pitate - Aabb <> Efficacy and safety of recombinant factor XIII on reducing blood transfusions in cardiac surgery: a randomized, placebo-controlled, multicenter clinical trial. Clinical use of plasma components - UpToDate Adult cardiac surgery, Fresh Frozen Plasma (FFP), Cryoprecipitate, Prothrombin Complex Concentrate (PCCs) The . Randomized patients received 4 g of fibrinogen concentrate or 10 units of cryoprecipitate. Medizinische Klinik, Intensivmedizin und Notfallmedizin. 6. 0000008132 00000 n The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. A compendium of transfusion practice guidelines American Red Cross Transfusion Practice Compendium. Witmer CM, Huang YS, Lynch K, Raffini LJ, Shah SS. 0000002297 00000 n In conclusion, current evidence suggests that the risk of transmission of SARS-CoV-2 through the blood supply is exceedingly low. RiaSTAP Fibrinogen Concentrate (Human). The treatment with fibrinogen concentrate will not replace VWF multimers, and poor platelet adhesion may persist despite normalization of fibrinogen. 17. A Comparison of Prothrombin Complex Concentrate and - PubMed After the FIBRES study, Health Canada also approved fibrinogen concentrate to treat acquired hypofibrinogenemia. 38. Prothrombin complex concentrate (Beriplex P/N) in severe bleeding: experience in a large tertiary hospital. 0000004011 00000 n basics of four-factor prothrombin complex concentrate . 0000006800 00000 n may email you for journal alerts and information, but is committed 0000014338 00000 n Vox Sang. Okerberg CK, Williams LA III, Kilgore ML, et al. [/CalRGB<>] Two of these donations were not utilized. Off-label recombinant factor VIIa use and thrombosis in children: a multi-center cohort study. <> No known transmission of other respiratory viruses (eg, severe acute respiratory syndrome or Middle East respiratory syndrome coronavirus) has occurred during the past 20 years through blood transfusion. endobj Get new journal Tables of Contents sent right to your email inbox, http://journals.lww.com/anesthesia-analgesia/pages/default.aspx, http://success.redcross.org/success/file.php/1/TransfusionPractices-Compendium_3rdEdition.pdf, https://www.fda.gov/media/105864/download, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=606.122, https://onlinelibrary.wiley.com/doi/10.1111/hae.14046, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood-establishments-regarding-covid-19-pandemic-and-blood-donation, Pro-Con Debate: Fibrinogen Concentrate or Cryoprecipitate for Treatment of Acquired Hypofibrinogenemia in Cardiac Surgical Patients, Articles in PubMed by Nadia B. Hensley, MD, Articles in Google Scholar by Nadia B. Hensley, MD, Other articles in this journal by Nadia B. Hensley, MD, Update on Applications and Limitations of Perioperative Tranexamic Acid, Society of Cardiovascular Anesthesiologists Clinical Practice Improvement Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients, Blood Conservation and Hemostasis in Cardiac Surgery: A Survey of Practice Variation and Adoption of Evidence-Based Guidelines, Intraoperative Management of Adult Patients on Extracorporeal Membrane Oxygenation: An Expert Consensus Statement From the Society of Cardiovascular AnesthesiologistsPart II, Intraoperative Management and Troubleshooting, Red Blood Cell Transfusion and Postoperative Infection in Patients Having Coronary Artery Bypass Grafting Surgery: An Analysis of the Society of Thoracic Surgeons Adult Cardiac Surgery Database, Privacy Policy (Updated December 15, 2022), International Anesthesia Research Society, Standard concentration of ~1 g per vial, after reconstitution becomes 1 g per 50 mL, Variable concentration of ~120796 mg per 15 mL in each individual single donor unit, Nucleic acid testing for HIV, hepatitis A, B, and C, and human parvovirus in donor plasma units, Nucleic acid testing for HIV, hepatitis B and C, and other viruses, Additional viral inactivation through precipitation/adsorption/pasteurization processes, Fibrinogen and other coagulation factors including VWF, FVIII, FXIII, fibronectin, and platelet microparticles, Secondary hemostasis by increasing substrate for thrombin, Primary hemostasis by increasing VWF and platelet microparticles, Secondary hemostasis by increasing substrate for thrombin and FVIII activity (intrinsic tenase activity), Rapid reconstitution in minutes can be rapidly administered to the patient after reconstitution, Kept frozen at 20 C and requires 3045 min to thaw, once available can be rapidly administered to the patient, Shelf life after reconstitution or thawing, Shelf life is up to 24 h after reconstitution, Limited shelf life after thawing of 46 h; FVIII activity degrades relatively quickly, fibrinogen is more stable, Negligible risk of alloimmunization, TACO, TRALI, Low, but present risk of allergic transfusion reactions, alloimmunization, and other transfusion adverse events (TACO or TRALI), Acquisition cost of ~$1000 per 1 g in the United States, lower acquisition cost in Europe and Canada of ~$400$500 per 1 g, Acquisition cost of ~$300$400 per 56 unit pool in the United States, Additional hidden costs include blood bank processing (~45 min to 1 h) and wastage, which increase the total cost, No detectable adverse events; 1 vein graft occlusion in the FC group; LIMA grafts patient in both groups, Elective AVR and ascending aorta replacement, Postbypass with signs of clinical bleeding, Dose based on the MCF on FIBTEM; mean, 5.7 0.7 g, Transfusion of allogeneic blood products after CPB in 24 h postop, Significantly fewer RBC, FFP, and platelet transfusions in the FC group, Significantly lower chest tube output in the FC group, Elective valve replacement/repair, double valve, or valve + CABG, Hemostatic scores similar between groups; no differences in RBC, FFP, cryo transfusions between groups; less platelets in the FC group, Elective complex surgery with >90 min CPB and at least 1 risk factor, Dose based on MCF on FIBTEM for target = 22 mm, Avoidance of any allogeneic blood products up to 30 d postop. 2013; 117:1422. J Pediatr. Theycontain fourvitamin K-dependent clotting factors (F) (II (prothrombin), VII, IX and X). Conflicts of Interest: N. B. Hensley has served on the scientific advisory board for Octapharma USA (Paramus, NJ) and received royalties from Wolters Kluwer for uptodate.com contributions. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. CFR-Code of Federal Regulations Title 21. 2020; 136:18881891. 58. [Level 5], Hellstern P, Production and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency. Lang T, Johanning K, Metzler H, et al. 54. 10>a Pharmacists can be an excellent resource in this setting, guiding clinicians concerning dosing and indications for administration and answering team members' questions about the medication. 27. 59. Blood. your express consent. Vox Sang. The site is secure. Pro-coagulant haemostatic factors for the prevention and treatment of bleeding in people without haemophilia. The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. 0000001394 00000 n There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. 33. Frontiers | Prothrombin Complex Concentrate in Liver Transplant Surgery Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery. 39. Some error has occurred while processing your request. Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patientsan economic evaluation. stream Adam EH, Meier J, Klee B, et al. trailer JAMA. 37. There was 1 vein graft occlusion in the fibrinogen concentrate group, and no vein graft occlusions in the control group. Safe in heart failure: PCC can be safely administered in patients with cardiac or renal impairment who may be unable totolerate large volumes of plasma. 91, No. X@YQLw`J]$aTCPZ-S]T&-m_KX]cIbX^}>u~krM.UleEw 2009; 88:14101418. 30. Epub 2017 Jul 12. Prothrombin Complex - an overview | ScienceDirect Topics Incidence of allo-immunization and allergic reactions to cryoprecipitate in haemophilia. 24. 55. 2015; 6:1935019351. When 5 single donor units are pooled together, this can be extrapolated to a minimum of 400 IU of factor VIII. The https:// ensures that you are connecting to the Prothrombin complex concentrate offers several advantages over FFP, most importantly, the small volume needed to reverse anticoagulation. The relationship between fibrinogen levels after cardiopulmonary bypass and large volume red cell transfusion in cardiac surgery: an observational study. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). The Journal of the American Osteopathic Association. Oncotarget. FFP contains coagulation factors at the same concentration present in plasma. 49. Prothrombin complex concentrate vs. fresh frozen plasma in adult Karlsson M, Ternstrm L, Hyllner M, et al. endobj . Journal of the American College of Cardiology. 2018 Dec 13 [PubMed PMID: 30548883], Levy JH,Tanaka KA,Dietrich W, Perioperative hemostatic management of patients treated with vitamin K antagonists. 51. [1]Processing techniques involving ion exchangers allow for the production of either three-factor (i.e., factors II, IX, and X) or four-factor (i.e., factors II, VII, IX, and X) PCC. Prophylactic fibrinogen infusion reduces bleeding after coronary artery bypass surgery. endobj Zhu N, Zhang D, Wang W, et al. 42. Recombinant activated factor VII is an excellent example of this phenomenon, where a clear pattern of increased thromboembolic risk was observed, as the drug was increasingly used off-label in the cardiac surgical patients.47,48. Life-threatening Major Bleed With a Non-Warfarin Anticoagulant. 0000000016 00000 n 0000014668 00000 n Alternatively, fibrinogen content is stable up to 5 weeks.14. The trial was stopped prematurely due to noninferiority being satisfied.24, Because cryoprecipitate is not a purified product and contains platelet microparticles, fibronectin, Factor VIII, and VWF, there may be an increased thromboembolic risk. 61. Fibrinogen and hemostasis: a primary hemostatic target for the management of acquired bleeding. None of these 43 trace-back repository samples were positive for SARS-CoV-2 RNA. Please enable scripts and reload this page. 35. Unauthorized use of these marks is strictly prohibited. HHS Vulnerability Disclosure, Help 0000011914 00000 n Explain the importance of improving care coordination among the interprofessional team to enhance care delivery for patients who can benefit from therapy with prothrombin complex concentrate. 0000002434 00000 n Implications for reducing donor exposure. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). The off-label utilization of prothrombin complex concentrate with Low levels of factor XIII are associated with increased postoperative bleeding and reoperation for bleeding in the cardiac surgery.55 Factor XIII administration was previously found to reduce blood loss in the CABG patients, when given at a dose of 1250 or 2500 IU.56 Unfortunately, these results were not replicated in a larger study of cardiac surgical patients, where 17.5 and 35 IU/kg doses were administered, and there was no reduction in allogeneic transfusion or reoperation.57 Nevertheless, in patients with excessive hemodilution or in those with major blood loss, the additional factor XIII activity that is present in the cryoprecipitate may be beneficial in achieving hemostasis. J Clin Invest. 2019; 59:32953297. When Heyde syndrome patients develop post-CPBacquired hypofibrinogenemia, they may be better served by the treatment with cryoprecipitate, which contains large VWF multimers. 29. The acquisition time for cryoprecipitate (3040 minutes) is considerably longer compared to fibrinogen concentrate because of the need to thaw cryoprecipitate. Hospital pharmacy. 2016; 116:208214. Full size image Patients in the FP group were slightly older, heavier, more likely to be male, and more likely to undergo non-elective surgery. <> The PCCs are standardized according to their factor IX content. There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Vol 26. Franchini M, Lippi G. Fibrinogen replacement therapy: a critical review of the literature. Thorac Cardiovasc Surg. 2017; 91:3947. The authors found that 67.2% of patients in the treatment arm avoided any allogeneic transfusion (primary outcome) compared to 44.8% in the control group (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.19-0.84). High-potency antihaemophilic factor concentrate prepared from cryoglobulin precipitate. Wolters Kluwer Health 22. 20. 2010 Jul [PubMed PMID: 20671873], Rowe AS,Mahbubani PS,Bucklin MH,Clark CT,Hamilton LA, Activated Prothrombin Complex Concentrate versus Plasma for Reversal of Warfarin-Associated Hemorrhage. The Surgical clinics of North America. PCC exists in two varieties: 3-factor PCC and 4-factor PCC. 12. 1979; 36:7780. 2018; 37:985991. PDF Anticoagulation Reversal Handout - EMCrit Project 2019; 322:111. 16. arch), Number of allogeneic blood product units (RBC, FFP, and platelets) in 24 h after FC, Median total of 5.0 (IQR, 2.011.0) units of allogeneic blood products in the FC group compared with 3.0 (IQR, 0.07.0) units in the placebo group, Intraoperative blood loss (mL) measured between intervention and chest closure, No significant differences in blood loss measured between the time of FC administration and chest closure. 2015; 4:e002066. endobj Repeat or subsequent dosing is not recommended. 2011; 15:R239. An official website of the United States government. <> 2018 Jun;52(6):533-537. doi: 10.1177/1060028017752365. startxref This will be the first prospective randomized controlled clinical trial directly comparing Prothrombin Complex Concentrate (PCC) Compared to Fresh Frozen Plasma (FFP) for post cardiopulmonary bypass microvascular bleeding and factor-mediated coagulopathy. Four-factor prothrombin complex concentrate in adjunct to whole blood Judith Graham Pool and the discovery of cryoprecipitate. 33 0 obj Pool JG, Gershgold EJ, Pappenhagen AR. Tanaka KA, Egan K, Szlam F, et al. Transfusion medicine reviews. 2017). Quick administration: The large amount of FFP takes much longer to infuse, whereas PCC can be administered over a few minutes and provides immediate reversal in life-threatening bleeding. Icheva V, Nowak-Machen M, Budde U, et al. WFH Guidelines for the Management of Hemophilia. J Thromb Haemost. This extrapolates to ~1 thromboembolic event per 23,300 doses of 4 g of fibrinogen concentrate or an absolute risk of 0.004%. In: Cochrane Database Syst Rev. For the primary end point, the use of allogeneic blood products, the fibrinogen concentrate group was transfused fewer RBC units (0.5 1.1 vs 2.4 1.1), fewer FFP units (0.2 0.6 vs 4.5 2.1), and fewer platelet units (0.0 0.0 vs 1.6 1.7).36. Today, the therapy for pharmacologically anticoagulated patients with ESLD presenting for liver . In the cases of severe hypofibrinogenemia, as occurs in massive transfusion, delayed treatment can be quite detrimental due to dilutional coagulopathy with a fixed-ratio RBC, FFP, and platelet transfusion. Thromb Haemost. FOIA We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Their main authorized indication is reversal of the effects of oral anticoagulants (vitamin K antagonists, VKAs). PCC contains significantly higher amounts of the clotting factors compared to FFP; one dose of PCC equals 8 to 16 units of FFP. Jeppsson et al40 randomized patients presenting for elective CABG surgery to receive either fibrinogen concentrate (2 g) before surgery or placebo and found that median postoperative blood loss at 12 hours was not significantly different between the 2 groups. JAMA. Mean 24-hour post-CPB cumulative allogeneic transfusions were 16.3 units (95% CI, 14.9-17.8) in the fibrinogen concentrate group and 17.0 units (95% CI, 15.6-18.6) in the cryoprecipitate group. Prothrombin Complex Concentrate Four factor PCC (Kcentra) is dosed on the amount of factor IX. Nascimbene A, Neelamegham S, Frazier OH, Moake JL, Dong JF. Cryoprecipitate has been available for transfusion since 1964; initially as therapy for haemophilia A, then rapidly becoming first line treatment for von Willebrand's disease and heritable deficiencies of fibrinogen and FXIII 1.With the advent of single-factor concentrate therapy the number of clinical indications for cryoprecipitate has reduced. Kalbhenn J, Schlagenhauf A, Rosenfelder S, Schmutz A, Zieger B. Bilecen et al42 randomized patients (n = 120) having complex cardiac surgery (CABG + valve, multivalve, aortic root, ascending aorta, or arch repair) to receive fibrinogen concentrate or placebo if there was post-CPB bleeding >60 mL after attempts at surgical hemostasis. Prothrombin complex concentrate versus fresh-frozen plasma for - PubMed The two groups were then compared for: correction of INR, time to correction of INR, thromboembolic complications, mortality, and cost of therapy. Administration of Prothrombin Complex Concentrate vs. Standard 4. Package insert. The specific antidote is not available (e.g., adexanet alfa for apixaban). JAMA. 3. 2010; 363:17911800. Reprints will not be available from the authors. 2017; 11:3339. These findings met the prespecified criteria for noninferiority. 0000014998 00000 n endobj The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. 26. The use of other products, including Cryoprecipitate, coronavirus disease (COVID-19) convalescent plasma, and plasma derivatives such as prothrombin complex concentrates (PCCs) and individual coagulation factor concentrates, are discussed in separate topic reviews. Subramaniyan R, Marwaha N, Jain A, Ahluwalia J. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. In this Pro-Con commentary article, we discuss the advantages and disadvantages of both products for treating acquired hypofibrinogenemia in the cardiac surgical patients. Epub 2023 Mar 15. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). 50. The risk of pathogen transmission is one of the primary reasons that cryoprecipitate was removed from European markets. US Food and Drug Administration. FIBRYNA. arch, TAA without prox. 40 0 obj Transfusion. Although the direct acquisition cost for fibrinogen concentrate is higher in the United States, this type of analysis does not take into account the cost associated with pathogen transmission.45 It is important to note that as Europe withdrew cryoprecipitate from its markets 15 years ago, it has not reversed course based on the new information. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Plasma fibronectin supports hemostasis and regulates thrombosis. Introduction. Ranucci M, Baryshnikova E, Crapelli GB, Rahe-Meyer N, Menicanti L, Frigiola A; Surgical Clinical Outcome REsearch (SCORE) Group. Haemophilia. Transfus Med Rev. Products Licensed in the US | National Hemophilia Foundation 31 However, there is continuing controversy over which component is preferable, and this, in part, reflects a lack of clinical trials comparing the two components. 62. Furthermore, evidence supporting the routine or prophylactic use of fibrinogen concentrate in the cardiac surgical patients is not robust, and larger studies are needed to confirm its value compared to cryoprecipitate, which has been the gold standard for treating acquired hypofibrinogenemia for almost 50 years. Although this may seem trivial, off-label drug use is associated with a 1.5-fold higher incidence of serious adverse drug events.46 Furthermore, a significant amount of pharmacovigilance time may be needed to identify a pattern of increased thromboembolic risk. Due to plasmas low fibrinogen content of 500600 mg per 250 mL, plasma fibrinogen concentration is likely to remain low, while awaiting cryoprecipitate.31, With any allogeneic transfusion, including cryoprecipitate, there is a risk of alloimmunization and allergic transfusion reaction.32 Fibrinogen concentrate undergoes viral inactivation processing, which also removes blood and human leukocyte antigen (HLA) antibodies and antigens and significantly reduces the risk of immunological transfusion reaction.12 Transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), and allergic transfusion reactions remain significant risks of allogeneic blood transfusion and are associated with increased health care cost, morbidity, and mortality.33,34. 60. 43. Bilecen S, de Groot JA, Kalkman CJ, et al. FIBRES - Effect of fibrinogen concentrate vs cryoprecipitate on blood component transfusion after cardiac surgery; 12 FP = frozen plasma; PCC = prothrombin complex concentrate. Four-factor prothrombin complex concentrate in adjunct to whole blood in trauma-related hemorrhage : Does whole blood replace the need for factors? Prothrombin complex concentrate (PCC) comes from the process of ion-exchange chromatography from the cryoprecipitate supernatant of large plasma pools and after removal of antithrombin and factor XI. %PDF-1.4 % Bachowski GBD, Brunker PAR, Eder A, et al. Kasper CK. The main reason for this is that factor VIII activity decreases quickly at room temperature. 47 0 obj PCC dosing products are expressed as units of factor IX. Wang Y, Carrim N, Ni H. Fibronectin orchestrates thrombosis and hemostasis. One vial of PCC also contains factors II, VII, IX, X, Proteins C and S, Antithrombin III and a small amount of heparin. Bleeding management with fibrinogen concentrate targeting a high-normal plasma fibrinogen level: a pilot study. 2017. Eguale T, Buckeridge DL, Verma A, et al. FC group 50 mL (29100) versus placebo 70 mL (33145), Cardiac surgery with CPB and fibrinogen replacement necessary, Postbypass with plasma fibrinogen level <2.0 g/L, Cumulative allogeneic blood product units (RBC, FFP, platelets), Noninferiority criteria met; mean 24 h postbypass cumulative transfusions 16.3 (95% CI, 14.9-17.8) vs 17.0 (95% CI, 15.6-18.6). FFP versus Cryoprecipitate - UpToDate endobj Fibrinogen, which is a plasma glycoprotein that is made in the liver (half-life of ~100 hours), is a critical substrate for thrombin. In a mixed-effects regression model for cumulative blood loss in the first 24 hours after surgery, the fibrinogen concentrate group was significantly lower with a median blood loss of 570 mL (IQR, 390730 mL) compared to 690 mL (IQR, 4001090 mL; P = .047). 31. For several years, FFP and vitamin K were the preferred options for reversing anticoagulation. Prothrombin complex concentrate vs fresh frozen plasma for reversal of Postmarketing surveillance reports angioedema, bronchospasm, and other severe thromboembolic complications (e.g., myocardial infarction, transient ischemic attack, and arterial thrombosis). Suggested treatment for active bleeding or invasive procedure prophylaxis has been described in the setting of end-stage liver disease (ESLD) in patients not receiving anticoagulation, and has included fresh frozen plasma (FFP), prothrombin complex concentrates (PCC), platelets, and cryoprecipitate. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. Am J Hematol. Cryoprecipitate (cryo) is enriched for 5 cold-insoluble proteins: fibrinogen; von Willebrand factor; factors VIII; and XIII; and . [11], Higher doses of PCC can increase the risk of thromboembolism. <> Br J Anaesth. Mazzeffi M, Hasan S, Abuelkasem E, et al.

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