Recombinant Factor VIIa Treatment of Severe Bleeding in Cardiac Surgery Patients: A Retrospective Analysis of Dosing, Efficacy, and Safety Outcomes

Masud, Faisal; Bostan, Fariedeh; Chi, Elisa; Pass, Steven E.; Samir, Hany; Stuebing, Karla K.; Liebl, Michael

doi:10.1053/j.jvca.2008.08.003

Cited by 33 publications

(35 citation statements)

References 37 publications

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“…Smaller doses showed satisfactory results in some off-label conditions, such as cardiac patients with intractable bleeding [4,28] and trauma patients with coagulopathy [5]. For instance, 1.2 mg effectively treated mild to moderate coagulopathy following injury, 1.2 mg and less than 90 μg/kg were effective for severe bleeding in cardiac surgery with few or no thrombotic events, and 20 μg/kg or 40 μg/kg resulted in a 50% reduction in blood loss in patients with a pre-existing normal coagulation system undergoing abdominal prostatectomy[29].…”

Section: Discussionmentioning

confidence: 99%

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

Altman¹,

Scazziota²,

Herrera³

et al. 2010

Thrombosis Journal

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BackgroundHigh concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro.MethodsLag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM).ResultsIn PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→35 min with no effect on PTG but were independent of rFVIIa concentration.ConclusionLow concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications.

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Section: Discussionmentioning

confidence: 99%

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

Altman¹,

Scazziota²,

Herrera³

et al. 2010

Thrombosis Journal

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“…Initially, doses of 40 to 80 μg/kg rFVIIa were used empirically based on published reports. However with the availability of 1-mg rFVIIa vials and reports of efficacy with lower rFVIIa doses [4, 5, 18], our practice evolved to the initial administration of 10 to 20 μg/kg (1-2 mg) rFVIIa, with the dose repeated if bleeding continued after a minimum of 15 minutes. Sternal closure and transfer to the ICU were not performed until hemostasis was achieved.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to multiple case reports and nonrandomized single-institution and large database studies, 2 randomized trials using rFVIIa doses between 40 and 90 μg/kg have documented the efficacy of rFVIIa in controlling hemorrhage when used in either the intraoperative or postoperative setting [1, 6]. In 2005, we proposed that low-dose rFVIIa (20–40 μg/kg) may be adequate to achieve hemostasis in patients with intact hemostatic systems [15], and other reports have since supported this approach [4, 5, 18–20]. The rationale for early rFVIIa dosing appears further supported by the findings of a large Canadian review of rFVIIa use in cardiac procedures, in which the authors concluded the efficacy of rFVIIa may be improved if administered early in the setting of adequate coagulation factors [11].…”

Section: Commentmentioning

confidence: 99%

“…However the safety of rFVIIa and optimal dosing strategy remain controversial. Although multiple studies have supported the safety of rFVIIa in cardiac operations [1–5, 7–13], randomized data and a recent meta-analysis of all studies with patient matching suggest an increased rate of stroke with rFVIIa therapy [6, 14]. Clouding the interpretation of these data is the wide variation in treatment protocols between centers.…”

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confidence: 99%

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Intraoperative Use of Low-Dose Recombinant Activated Factor VII During Thoracic Aortic Operations

Andersen

Bhattacharya

Williams

et al. 2012

The Annals of Thoracic Surgery

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Background Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Methods Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Results Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16–43 μg/kg) rFVIIa given 51 minutes (42–67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p = 0.05; international normalized ratio, 0.8 versus 1.2; p < 0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p = 0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Conclusions Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach.

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“…Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) is a novel hemostatic agent, which has been proven effective for the management of hemorrhage after cardiac surgery [3]-[5]. Although multiple studies have supported the efficacy and safety of rFVIIa in cardiac operations [2]-[7], there are concerns regarding the optimal dosage of rFVIIa and the timing of rFVIIa administration [6],[7].…”

Section: Introductionmentioning

confidence: 99%

Combination use of platelets and recombinant activated factor VII for increased hemostasis during acute type a dissection operations

Wen

Xuan

et al. 2014

J Cardiothorac Surg

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BackgroundRefractory blood loss is a common problem in surgeries for acute type A aortic dissections. Significant evidence has supported the benefit of using recombinant activated factor VII (rFVIIa) to control of intractable bleeding in patients after cardiac surgery. In this prospective clinical study, we present a novel method to achieve intraoperative hemostasis by using a combination of platelets and rFVIIa during operations for acute type A aortic dissections.MethodsBetween May 2009 and August 2012, 71 patients with acute type A dissections who underwent emergency surgery were prospectively included and allocated to one of the following two intervention groups for hemostasis: 3 units platelets combined with 2.4 mg rFVIIa (n = 25), and conventional methods (n = 46).ResultsThe patients who received the combination of platelets and rFVIIa required fewer transfusions of red blood cells (6.2 ± 3.1 units vs 9.8 ± 2.8 units; p < 0.05), fresh frozen plasma (736.9 ± 178.3 ml vs 1264.3 ± 245.2 ml, p < 0.05), platelet concentrates (3 units vs 5.0 ± 1.8 units, p < 0.001), and cryoprecipitate (2.8 ± 0.9 units vs 8.2 ± 2.3 units, p < 0.05). These patients also required less time for sternal closure (76.9 ± 17.2 min vs 102.3 ± 10.7 min, p < 0.05) compared with the conventional therapy patients. There was no statistically significant difference in the incidence of serious adverse events between these two groups.ConclusionsUsing a combination of platelets and rFVIIa is an effective strategy for achieving hemostasis during acute type A dissection surgery. This hemostatic strategy does not appear to be associated with an increase in postoperative adverse events.Electronic supplementary materialThe online version of this article (doi:10.1186/s13019-014-0156-y) contains supplementary material, which is available to authorized users.

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Recombinant Factor VIIa Treatment of Severe Bleeding in Cardiac Surgery Patients: A Retrospective Analysis of Dosing, Efficacy, and Safety Outcomes

Cited by 33 publications

References 37 publications

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

Intraoperative Use of Low-Dose Recombinant Activated Factor VII During Thoracic Aortic Operations

Combination use of platelets and recombinant activated factor VII for increased hemostasis during acute type a dissection operations

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