Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven®): a propensity score analysis

Gelsomino, Sandro; Lorusso, Roberto; Romagnoli, Stefano; Bevilacqua, Sergio; Cicco, Giuseppe De; Billè, Giuseppe; Stefàno, Pierluigi; Gensini, Gian Franco

doi:10.1016/j.ejcts.2007.10.004

Cited by 57 publications

(58 citation statements)

References 21 publications

(20 reference statements)

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“…Reduced bleeding is observed in propensity-matched studies when cardiac surgery patients receive low dose rFVIIa compared with placebo. 64,67 Intuitively, fewer adverse thromboembolic effects would be expected with lower doses of rFVIIa, and the higher doses (70 – 90 µg/kg) used for bypassing activity in hemophiliacs are unnecessary in the non-hemophiliac surgical patient because the intrinsic Xase enzyme complex is intact. Failure to address platelet, fibrinogen, Factors II, VIII, IX or X deficiencies in patients with severe hemorrhage will limit the effectiveness of rFVIIa to restore thrombin generation and fibrin clot formation (Figure 1, normal coagulation model).…”

Section: Approved and Off-label Uses For Pccsmentioning

confidence: 99%

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Ghadimi

Levy²,

Welsby³

2016

Anesthesia &Amp; Analgesia

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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 dependent on the concentrations of Factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but as with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and individual patient prothrombotic predisposition. PCCs are Food and Drug Administration approved for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and therefore can be administered in these patients when urgent surgery is required. There is, however, a 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 laboratory and clinical variables, including point-of-care coagulation testing, in order to balance hemostatic benefits while minimizing 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.

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Section: Approved and Off-label Uses For Pccsmentioning

confidence: 99%

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Ghadimi

Levy²,

Welsby³

2016

Anesthesia &Amp; Analgesia

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“…70,71 Investigators in one propensity-matched study administered 10 to 15 IU/kg of 4F-PCCs before low-dose rFVIIa (median, 18 μg/kg; interquartile range, 9-16 μg/kg) and found reduced bleeding after cardiac surgery. 67 This combination of low-dose rFVIIa and PCCs may confer advantages over the use of rFVIIa alone. There is insufficient evidence, however, to support this approach without using point-of-care and laboratoryguided testing within an algorithm for refractory bleeding to help prevent thromboembolic disease.…”

Section: 61mentioning

confidence: 99%

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Ghadim

Levy

Welsby

2016

Survey of Anesthesiology

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“…This finding is consistent with several smaller studies in cardiac surgery that have found that patients who receive rFVIIa have risk-adjusted complication rates similar to those who do not receive rFVIIa. 14,[33][34][35] Importantly, by adjusting for RBC transfusions in this analysis, we have discounted the potential benefits of rFVIIa in reducing blood loss, thereby enhancing our ability to detect the risks of rFVIIa. It is important to note, however, that the severity of patients' underlying risk status and the high complication rates in this and most other studies may mask clinically important modulations in risk caused by rFVIIa therapy.…”

Section: Safety and Predictors Of Adverse Eventsmentioning

confidence: 99%

Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery

et al. 2008

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Background-This observational study sought to identify the off-label use pattern of recombinant activated factor VII (rFVIIa) in cardiac surgery and to identify predictors of its effectiveness and risk. Methods and Results-At 18 Canadian centers, 522 nonhemophiliac cardiac surgical patients received rFVIIa during the period 2003 through 2006; data were available, and retrospectively collected, on 503 patients. The median (quartile 1, quartile 3) units of red blood cells transfused from surgery to therapy and in the 24 hours after therapy were 8 (5, 12) and 2 (1, 5), respectively (PϽ0.0001). Mortality rate was 32%, and mortality or major morbidity rate was 44%. These rates were within expected ranges (mortality, 27% to 35%; mortality or morbidity, 39% to 48%), which were calculated with a separate cohort of cardiac surgical patients who did not receive rFVIIa used as reference. Independent predictors of complications included instability before therapy (multiple inotropes or intra-aortic balloon pump) and increasing red blood cell units transfused before and after therapy. Variables independently associated with nonresponse included abnormal coagulation parameters and Ͼ15 red blood cell units transfused before therapy. Conclusions-In Canada, rFVIIa is used primarily when standard interventions have failed to control bleeding. In this setting, rFVIIa is associated with reduced blood product transfusions and, after risk adjustment, does not appear to be associated with increased or decreased complication rates. The effectiveness of the drug may be enhanced if it is given early in the course of refractory blood loss in the setting of adequate amounts of circulating coagulation factors.

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Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven®): a propensity score analysis

Abstract: In our experience low-dose rFVIIa was associated with reduced blood loss, improvement of coagulation variables and decreased need for transfusions. Our findings need to be confirmed by further larger studies.

Cited by 57 publications

References 21 publications

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Prothrombin Complex Concentrates for Bleeding in the Perioperative Setting

Comprehensive Canadian Review of the Off-Label Use of Recombinant Activated Factor VII in Cardiac Surgery

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