A Study Using Prothrombin Complex Concentrate versus Fresh Frozen Plasma for Post Cardiopulmonary Bypass Surgery Clotting Problems and Bleeding

Overview

  • Study type

    Interventional
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Site IRB
    • Rochester, Minnesota: 14-009579
    NCT ID: NCT02557672
    Sponsor Protocol Number: 14-009579

About this study

The purpose of this study is to directly compare prothrombin complex concentrate to fresh frozen plasma for microvascular bleeding and factor-mediated clotting disorder post cardiopulmonary bypass surgery. 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Be ≥ 18 years of age.
  • Be undergoing a cardiac surgical procedure utilizing cardiopulmonary bypass.
  • Have an INR ≤ 1.3, or no documented INR, if warfarin was held for 5 days or more.
  • Have an INR ≤ 1.3 if warfarin was not held for 5 days.

Exclusion Criteria:

  • Are unable to grant informed consent or comply with study procedure.
  • History of hypercoagulable condition (e.g. Factor V Leiden, AT-3 deficiency, Prothrombin gene mutation, Anti-phospholipid antibody syndrome, etc.) or previous unprovoked thromboembolic complications.
  • Coagulopathic conditions such as factor deficiencies, factor inhibitors, heparin induced thrombocytopenia, or use of intravenous anticoagulants other than heparin at the time of cardiovascular surgery.
  • Thromboembolic event with past 3 months.
  • Received oral therapy with ELIQUIS (apixaban) within 3 days prior to planned surgical procedure.
  • Received oral therapy with clopidogrel,prasugrel, rivaroxaban or dabigatran within 5 days prior to planned surgical procedure.
  • Are undergoing emergency open heart-surgery.
  • Cardiopulmonary bypass time is expected to be < 30 minutes.
  • Are pregnant.
  • Heparin allergy.
  • ECMO post op.

Enrolled subjects must meet additional criteria in order to receive study treatment:

Inclusion Criteria:

  • Have evidence of excessive microvascular bleeding in the surgical field as determined by the surgical team.
  • PT >16.6 sec/ INR >1.6 sec, or aPTT > 57 sec. on initial post-cardiopulmonary bypass labs.

Exclusion Criteria:

  • Fibrinogen < 144 mg/dL on initial post cardiopulmonary bypass labs.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Gregory Nuttall, M.D.

Open for enrollment

Contact information:

Kristal Young

More information

Publications

Administration of coagulation factor concentrates to treat bleeding after cardiac surgery with cardiopulmonary bypass might be a strategy for reducing allogeneic blood transfusions, particularly for patients treated with warfarin preoperatively. We performed an exploratory analysis on whether the use of prothrombin complex concentrate (PCC) is safe and effective compared with fresh frozen plasma (FFP) to treat coagulopathy after pulmonary endarterectomy surgery with deep hypothermic circulatory arrest. Read More on PubMed
Coagulopathy after cardiac surgery with cardiopulmonary bypass is a serious complication that may result in massive bleeding requiring transfusion of significant amounts of blood products, plasma, and platelets. In addition to increased patient morbidity and mortality it is associated with longer hospital stay and increased resource utilization. The current review discusses aspects in cardiopulmonary bypass-induced coagulopathy with emphasis on point-of-care testing and individualized "goal-directed" therapy in patients who develop excessive bleeding after cardiac surgery. Read More on PubMed
Managing patients in the perioperative setting receiving novel oral anticoagulation agents for thromboprophylaxis or stroke prevention with atrial fibrillation is an important consideration for clinicians. The novel oral anticoagulation agents include direct Factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran. In elective surgery, discontinuing their use is important, but renal function must also be considered because elimination is highly dependent on renal elimination. If bleeding occurs in patients who have received these agents, common principles of bleeding management as with any anticoagulant (including the known principles for warfarin) should be considered. This review summarizes the available data regarding the management of bleeding with novel oral anticoagulation agents. Hemodialysis is a therapeutic option for dabigatran-related bleeding, while in vitro studies showed that prothrombin complex concentrates are reported to be useful for rivaroxaban-related bleeding. Additional clinical studies are needed to determine the best method for reversal of the novel oral anticoagulation agents when bleeding occurs. Read More on PubMed
Prothrombin complex concentrate (PCC) is an inactivated concentrate of factors II, IX, and X, with variable amounts of factor VII. Guidelines recommend the use of PCC in the setting of life-threatening bleeds, but little is known on the most effective dosing strategies and how the presenting international normalized ratio affects response to therapy. Read More on PubMed
The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. Read More on PubMed
Prothrombin complex concentrates (PCCs) are sometimes used as 'off label' for excessive bleeding after cardiopulmonary bypass (CPB). The main objective of this study was to retrospectively evaluate the clinical and biological efficacy of PCC in this setting. Read More on PubMed
The acute respiratory distress syndrome (ARDS) was defined in 1994 by the American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg), moderate (100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg), and severe (PaO2/FIO2 ≤ 100 mm Hg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min). The draft Berlin Definition was empirically evaluated using patient-level meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%; 95% CI, 24%-30%; 32%; 95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P < .001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P < .001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553; P < .001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning. Read More on PubMed
Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh-frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion-related acute lung injury, 2) transfusion-associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. Read More on PubMed
The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed. Read More on PubMed
High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Read More on PubMed
Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion-related mortality in most developed countries. Despite this fact, well-designed investigations on specific management strategies for TRALI are lacking. Indeed, current recommendations are primarily based on data extrapolated from trials of the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress Syndromes. The cornerstone of TRALI management is supportive care with oxygen supplementation and ventilatory assistance when needed. When mechanical ventilation is required, attenuating additional ventilator-induced lung injury through the avoidance of high tidal volumes and elevated airway pressures, with additional measures such as positive end-expiratory pressure to prevent low-volume shear stress injury, are recommended. The literature is not currently sufficient to support either corticosteroids or statins as effective therapies in TRALI. Conservative fluid practices are desirable, provided care is taken to avoid hypotension. Preventative strategies have shown the most promise in mitigating this transfusion-related pulmonary complication. Specifically, conservative transfusion practices and deferral of high-plasma component donors who have, or at high risk of having, anti-human leukocyte antigen and/or anti-human neutrophil antigen antibodies have meaningfully impacted the incidence of TRALI. Future considerations for patients who are at increased risk for developing TRALI may include therapies such as anti-platelet agents and alternatives to traditional blood components such as prothrombin complex concentrates (PCC). However, these potential TRALI prevention strategies are insufficiently studied, have unclear risk/benefit profiles and cannot be currently recommended. Read More on PubMed
Blood transfusion is associated with increased morbidity and mortality. We developed and implemented an algorithm for coagulation management in cardiovascular surgery based on first-line administration of coagulation factor concentrates combined with point-of-care thromboelastometry/impedance aggregometry. Read More on PubMed
Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Read More on PubMed
Fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC) reverse oral anticoagulants. We compared PCC and FFP intraoperative administration in patients undergoing heart surgery with cardiopulmonary bypass (CPB). Read More on PubMed
Cardiopulmonary bypass has been shown to be associated with platelet dysfunction, which has a potential for increasing the risk of perioperative bleeding. Off-pump coronary artery bypass surgery is thought to avoid this deleterious effect of pump use on platelets. However, the influence of off-pump coronary artery bypass surgery on platelets has not been thoroughly studied. Read More on PubMed
Transfusion-related acute lung injury (TRALI) is now the leading cause of transfusion-associated mortality, even though it is probably still underdiagnosed and underreported. Read More on PubMed
Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. Read More on PubMed

Study Results Summary

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Supplemental Study Information

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CLS-20206535

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