| Author, Year |
Description of Study |
Patients (n) |
Dose of Recombinant Activated Factor VII |
Dosing Strategy (Rescue or Prophylactic) |
Outcomes |
Adverse Events |
| Blinded randomized, controlled trial, variable dose recombinant activated factor VII |
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| Payani, et al. 37 2015 |
Randomized, controlled trial |
Redo valve surgery (18) |
40 mcg/kg |
Prophylactic, placebo-controlled. Patients received recombinant activated factor VII or placebo if enrolled, regardless of bleeding status after bypass. |
Fewer patients with required transfusions in recombinant activated factor VII arm (3) than in placebo (13). No difference in chest tube drainage at 3rd and 12th h postoperatively, but less at 24 h in recombinant activated factor VII group. |
Ventilation time was longer in placebo group. No difference in ICU stay or thromboembolic events. |
| Essam, et al. 38 2013 |
Randomized, controlled trial |
Coronary revascularization surgery (30) |
90 mcg/kg |
Prophylactic, placebo-controlled. Patients received recombinant activated factor VII or placebo if enrolled, regardless of bleeding status after bypass. |
Decreased transfusions, chest tube drainage, and more normalized coagulation laboratory studies in recombinant activated factor VII group. |
No report of adverse events. |
| Gill, et al. 36 2009 |
Randomized, controlled trial |
Cardiac surgical; 30 sites in 13 countries (172) |
Either: placebo (n = 68), 40 mcg/kg (n = 35), 80 mcg/kg (n = 69) |
Study agent given for bleeding refractory to other management after prespecified rate of bleeding met. |
More critical serious adverse events in 33 days postoperatively (renal failure, stroke, intestinal infarction, multiorgan dysfunction, sepsis, low cardiac output, myocardial infarction, cardiac arrest, electromechanical dissociation) in recombinant activated factor VII groups, although not statistically significant. Fewer reoperations and transfusions in recombinant activated factor VII patients. |
No significant differences in death, stroke, myocardial infarction, pulmonary embolism, or other thromboembolic events. |
| Ma, et al. 39 2006 |
Randomized, controlled trial |
Cardiac valve surgery (28) |
40 mcg/kg |
Prophylactic, placebo-controlled. Patients received recombinant activated factor VII or placebo if enrolled, regardless of bleeding status after bypass. |
Less chest tube drainage, transfusions, ventilation time, ICU stay, and normalized coagulation laboratory tests in recombinant activated factor VII group. Costs not different among groups. |
No difference in thrombotic events, cardiac events, or death. |
| Diprose, et al. 35 2005 |
Randomized, controlled trial |
Complex cardiac surgery (20) |
90 mcg/kg |
Prophylactic, placebo-controlled. Patients received recombinant activated factor VII or placebo if enrolled, regardless of bleeding status after bypass. |
Fewer patients required transfusions in recombinant activated factor VII arm (n = 2) compared with placebo (n = 8). Fewer products overall to recombinant activated factor VII group. |
No difference in stroke, myocardial infarction, death, ICU stay or ventilator time. |
| High-dose recombinant activated factor VII studies |
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| Marsh, et al. 60 2020 |
Retrospective, observational review |
Majority (81%) cardiac surgical patients
(63: 6 pediatric; 57 adults) |
20–80 mcg/kg |
Primary outcome: administered strategy. Recombinant activated factor VII given for various etiologies of bleeding (hemophilia, pulmonary hemorrhage, atrial fibrillation ablation bleeding, hemothorax). |
Recombinant activated factor VII administration decreased after protocol implementation. Recombinant activated factor VII use reduced blood product administration. |
Thromboembolic events within 30 days = 19.6% with 70% of these occurring in patients > 70 yr old |
| Feih, et al. 42 2019 |
Retrospective, observational |
Cardiac surgical (58) |
Initial dose of 5.1 mg (65 ± 23 mcg/kg) |
Bleeding refractory to other management. |
Patients with adequate coagulation resuscitation before recombinant activated factor VII administration were more likely to achieve successful hemostasis. |
No differences in thromboembolic events or mortality. |
| Zindovic, et al. 61 2017 |
Retrospective, propensity matched |
Acute type A aortic dissection repair; multicenter trial (120 matched pairs) |
No dosing information |
Management of bleeding varied depending on the center and time. Recombinant activated factor VII given mostly for bleeding refractory to other management. |
Patients receiving recombinant activated factor VII received more blood products and underwent reexploration for bleeding more often. |
No differences in in-hospital mortality, stroke or need for renal replacement therapy. |
| Alfirevic, et al. 43 2014 |
Retrospective, propensity matched |
Complex cardiac surgical (144 matched pairs) |
20–90 mcg/kg and repeated as needed |
Protracted bleeding and severely refractory to blood and products. |
40% of patients who received recombinant activated factor VII died compared with 18% of controls. Recombinant activated factor VII associated with more renal morbidity. High-dose recombinant activated factor VII (> 60 mcg/kg) did not increase the risk for mortality compared with treatment with low-dose recombinant activated factor VII (< 60 mcg/kg). |
Thromboembolic and neurologic complications were not different among groups. |
| Tritapepe, et al. 44 2007 |
Retrospective, propensity score matched |
Acute aortic dissection repair with deep hypothermic circulatory arrest (23 matched pairs) |
70 mcg/kg; 4 patients required repeat dose |
Bleeding refractory to other management |
Blood loss and transfusions reduced after recombinant activated factor VII. Improvement in laboratory measurements of coagulation. |
No differences in adverse events. |
| Karkouti, et al. 45 2006 |
Retrospective, matched |
Cardiac surgical (114) |
2.4–2.8 mg initial dose, followed by repeat |
Refractory, excessive blood loss |
Among recombinant activated factor VII recipients, earlier administration (<8 erythrocyte transfusions) correlated with lower risk of adverse events. |
No difference in any adverse events between patients who received rFVIIa and those who did not. |
| Von Heymann, et al. 46 2005 |
Retrospective, matched analysis with historic controls. |
Cardiac surgical (24 matched pairs) |
12 patients received 60 mcg/kg;
10 patients received median 116 mcg/kg;
2 patients received median 187 mcg/kg |
Bleeding refractory to other management; "last resort" |
Blood loss and transfusions reduced in patients receiving recombinant activated factor VII at 14 h, but no differences at 24 h |
No thromboembolic complications in recombinant activated factor VII patients. No difference in ICU stay, mortality. |
| Karkouti, et al. 28 2005 |
Retrospective, propensity score matched |
Cardiac surgical (51 matched pairs) |
2.4 or 4.8 mg; 35–70 mcg/kg with repeat dosing in some |
Bleeding refractory to other management; "intractable hemorrhage" |
Blood loss and blood product usage were significantly decreased in recombinant activated factor VII patients |
Higher incidence of acute renal dysfunction but not need for hemodialysis. |
| Low-dose recombinant activated factor VII studies (< 40 mcg/kg) |
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| Goksedef, et al. 47 2012 |
Retrospective, propensity matched |
Aortic root, arch, or ascending replacement surgeries (58 matched pairs) |
Mean dose 23 ± 12 mcg/kg |
Bleeding refractory to other management |
Fewer reexplorations, fewer prolonged intubations, less total chest tube output, fewer units of transfusions in patients receiving recombinant activated factor VII. |
No differences in mortality, duration of ICU stay or thrombotic complications. |
| Andersen, et al. 48 2012 |
Retrospective, propensity matched |
Thoracic aortic surgical (44 matched pairs) |
Initial median dose 32 mcg/kg [interquartile range 16–43 mcg/kg] |
Severe coagulopathy refractory to other management |
Recombinant activated factor VII improved laboratory measurements of coagulation and decreased transfusions |
No differences in stroke, thromboembolism, myocardial infarction, or other adverse events. |
| Very-low-dose recombinant activated factor VII studies (< 20 mcg/kg) |
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| Sutherland, et al. 53 2022 |
Retrospective 3-way match based on how many hemostatic products given before recombinant activated factor VII |
Cardiac surgical (214) |
Median dose 13 mcg/kg |
Bleeding not deemed to be surgical in nature. Analyzed based on how many hemostatic agents (platelet, fresh frozen plasma, PCC) given before recombinant activated factor VII: (a) 0–1, (b) 2–4, (c) ≥5. |
Decrease in length of ICU stay, renal failure, total allogeneic transfusions in patients who received recombinant activated factor VII earliest (group 1 = after ≤1 other hemostatic agent received). |
No difference in adverse outcomes |
| Cotter, et al. 54 2021 |
Retrospective matched cohort |
Cardiac surgical (182 matched pairs) |
Median dose 13 mcg/kg |
Surgical team discretion for nonsurgically correctable bleeding |
Decrease in erythrocyte transfusion, renal risk, and length of hospital stay |
No increase in thromboembolism, mortality, or other adverse events. |
| Hoffmann, et al. 49 2018 |
Prospective, propensity analysis |
Cardiac surgical (281 patients; 167 received recombinant activated factor VII)
(6 patients had ventricular assist device, 6 had ECMO) |
< 20 mcg/kg |
Bleeding refractory to other management |
Complete hemostasis without need for further hemostatic treatment was achieved more often in recombinant activated factor VII recipients (88% vs. 0%) |
No differences in mortality, thromboembolic events, renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, hospital stay or readmission. |
| Brase, et al. 52 2015 |
Retrospective, propensity-matched |
Cardiac surgical (51 matched pairs) |
Median 12 mcg/kg |
Recombinant activated factor VII administered at surgical team discretion in bleeding patients. 13% received recombinant activated factor VII as first-line bleeding management, 12% receiving recombinant activated factor VII after one hemostatic blood product and 75% received recombinant activated factor VII after two or more blood products. |
Patients receiving recombinant activated factor VII had increased ventilator time and ICU stay. No differences in reoperations or hospital stay. |
No differences in mortality, acute kidney injury, infection, or thromboembolic events. |
| Gelsomino, et al. 27 2008 |
Retrospective, propensitymatched |
Cardiac surgical (40 matched pairs) |
Median 18 mcg/kg [interquartile range 9–16 mcg/kg] |
Bleeding refractory to other management |
Recombinant activated factor VII reduced 24-h blood loss, reduced transfusion requirements, decreased ICU stay and ventilation time |
No thromboembolic events reported, although 2 patients in rFVIIa group had postoperative strokes – neither thought to be related to treatment. |
| Romagnoli et al. 50 2006 |
Retrospective, case-control |
Cardiac surgical (15 matched pairs) |
1.2 mg or median 17 mcg/kg [interquartile range 11–21 mcg/kg] with repeat dose as needed |
"Intractable" bleeding refractory to other management |
Patients receiving recombinant activated factor VII had decreased blood loss and transfusions in recombinant activated factor VII group.
Improvement in laboratory coagulation measurements.
Reduced ICU stay and fewer reexplorations |
Patients receiving rFVIIa had more complications (conglomerate of stroke, renal failure, respiratory failure, low-output syndrome and infection) |
| Heart and lung transplantation |
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| Huddleston, et al. 62 2020 |
Retrospective, observational with 6-yr follow-up |
Lung transplant (38) |
Dose not given |
Algorithm for recombinant activated factor VII not given |
Packed red blood cell administration had signal to increased mortality with >15 units significantly increasing mortality. Recombinant activated factor VII did not increase risk of mortality. |
No information on thrombotic events |
| Hollis, et al. 63 2016 |
Retrospective, propensity-matched |
Heart transplant (21) |
Median dose 4.5 mg; total dose 2–10 mg or 24–111 mcg/kg |
No specific algorithm for recombinant activated factor VII administration |
No decrease in postoperative bleeding; however, significantly higher cost in recombinant activated factor VII group. |
No difference in thrombotic events |
| Bhaskar, et al. 64 2013 |
Retrospective |
Lung transplant (15) |
40–120 mcg/kg |
Refractory bleeding after blood products |
Recombinant activated factor VII treatment was not associated with increased mechanical ventilation time, ICU stay, or hospital stay. Recombinant activated factor VII was associated with reduction in transfusion requirements. |
No information on thrombotic events |
| Gandhi, et al. 41 2007 |
Retrospective |
Ventricular assist device explant to heart transplant (9)
Left ventricular assist device (5)
Heart transplant (1)
Unknown (2) |
Mean dose 78.3 mcg/kg (24–189 mcg/kg) in 1–3 doses |
Intractable bleeding unresponsive to multimodal therapy |
Decreased bleeding and erythrocyte transfusion after recombinant activated factor VII |
5/17 (2/10 transplants) developed thromboembolic complications, but "multimodal hemostatic therapy cannot be excluded as cause" |
| Mechanical support |
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| Anselmi, et al. 65 2016 |
Retrospective, case-matched |
Venoarterial and venovenous ECMO (23 recombinant activated factor VII patients matched with 43 non– recombinant activated factor VII patients) |
60 mcg/kg initial dose, no information on repeating |
After targeted transfusion thresholds |
93% of patients achieved hemostasis |
No differences observed among groups in terms of thromboembolic events, circuit change, ventilation time, infectious complications and survival at both ECMO explanation, 30-day mortality or late survival. |
| Karimi, et al. 66 2015 |
Retrospective |
Heartmate II left ventricular assist device (16) |
Average dose 70 ± 31 mcg/kg |
Refractory bleeding despite adequate blood component replacement |
Recombinant activated factor VII received more transfusions. Chest tube output decreased after recombinant activated factor VII administration |
No thromboembolic events occurred within 30 days |
| Repesse, et al. 67 2013 |
Retrospective, observational |
Venoarterial and venovenous ECMO (15) |
60 mcg/kg initial dose and may repeat |
Intractable hemorrhage after other allogeneic transfusions |
All but one patient had dramatic decrease in bleeding |
One patient had possible major stroke and 2 circuits required changing in 48 h post-recombinant activated factor VII due to clots and decreased oxygenation |
| Bruckner, et al. 68 2009 |
Retrospective |
Left ventricular assist device (62) |
Single dose of 10–20 mcg/kg (n = 32) as "low-dose" cohort; 30–70 mcg/kg (n = 30) as "high-dose" cohort |
"Patients were given recombinant activated factor VII only after surgical hemostasis and significant blood product transfusion had occurred" |
Improved laboratory measurements of coagulation. Fewer transfusions required after receiving recombinant activated factor VII than before receiving. |
Increased thromboembolic events in patients who received 30–70 mcg/kg rFVIIa compared with 10–20 mcg/kg |
