scholarly journals Antithrombotic and hemostatic stewardship: evaluation of clinical outcomes and adverse events of recombinant factor VIIa (Novoseven®) utilization at a large academic medical center

2020 ◽  
Vol 14 ◽  
pp. 175394472092425 ◽  
Author(s):  
Kassandra Marsh ◽  
David Green ◽  
Veronica Raco ◽  
John Papadopoulos ◽  
Tania Ahuja
Keyword(s):  
Cardiac Surgery ◽  
Adverse Events ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Academic Medical Center ◽  
Blood Bank ◽  
Thromboembolic Events ◽  
Blood Products ◽  
New York University ◽  
Off Label

Background: Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. Methods: We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. Results: A total of 63 patients [pediatric ( n = 6), adult ( n = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. Conclusion: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.

Off-Label Use of Recombinant Factor VIIa in United States Hospitals: 2000-2008.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 67-67
Author(s):  
Aaron C. Logan ◽  
Veronica Yank ◽  
Randall S. Stafford
Keyword(s):  
United States ◽  
Cardiac Surgery ◽  
Hospital Mortality ◽  
Intracranial Hemorrhage ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Off Label Use ◽  
Off Label ◽  
Academic Hospitals ◽  
Label Use

Abstract Abstract 67 Background: Recombinant factor VIIa (rFVIIa) is FDA-approved for treatment of bleeding due to factor VIII or factor IX inhibitors in the setting of congenital or acquired hemophilia or due to congenital factor VII deficiency. When first introduced into clinical practice in 1999, rFVIIa was used predominantly for these labeled indications. Over the years since it became widely available, rFVIIa has been employed extensively for off-label indications. The data to support these uses are sparse or, in some cases, contradictory. Objective: To estimate patterns of off-label rFVIIa use in United States hospitals. Data source: We evaluated data from the Premier Perspectives database of United States hospitals. This representative sample was used to extrapolate national usage patterns of rFVIIa. For each hospitalization at member institutions, the database includes information on patient demographics, primary and secondary diagnoses, medications dispensed, service items used, and disposition at discharge. We examined data encompassing hospitalizations between January 1, 2000 and December 31, 2008. Results: Use of rFVIIa was reported in 235 of 615 hospitals (38%) in the Premier database. 12,644 hospitalizations involving administration of rFVIIa during the study period were identified. Based on statistical weights for each member hospital, this translates to an estimated 73,747 hospitalizations nationwide during which rFVIIa was employed, 18,311 (25%) of which occurred during 2008. Between 2000 and 2008, off-label use of rFVIIa increased more than 140-fold, such that in 2008, 97% of in-hospital indications were off-label. In contrast, in-hospital use for the hemophilias has increased 3.7-fold since 2000 and appears to have plateaued, such that on-label use accounted for only 4.2% of use overall and 2.7% of use in 2008. We found cardiac surgery (29% of use in 2008), trauma (28%), and intracranial hemorrhage (11%) to be the most common off-label indications for rFVIIa use. Consistent with the growth of these and other off-label indications, there has been a significant increase in the mean age of patients receiving rFVIIa from 3 years in 2000 to 59 years in 2008. Conditions with a prominent proportion of use in the elderly (>65 years) included aortic aneurysm (82%), prostatectomy (66%), brain trauma (64%), intracranial hemorrhage (58%), cardiac surgery (57%), and gastrointestinal bleeding (57%). Across all indications, in-hospital mortality has increased substantially over time from 5% in 2000 to 27% in 2008. The highest in-hospital mortality rates were associated with aortic aneurysm (57%), neonatal use (54%), variceal bleeding (51%), other liver disease (49%), liver biopsy (45%), vascular procedures (43%), intracranial hemorrhage (43%), brain trauma (40%), body trauma (36%), and gastrointestinal bleeding (35%). The population receiving rFVIIa for the most common indication, adult cardiac surgery, experienced 24% in-hospital mortality. Amongst all patients treated with rFVIIa in 2008, 43% were discharged to home. Most of the remaining patients were transferred to other facilities, including nursing homes, rehabilitation hospitals, and other acute care facilities. In contrast, hemophilia patients receiving rFVIIa experienced a 3.8% in-hospital mortality rate, while 85% were discharged directly home. Finally, we identified a significant shift in rFVIIa use from academic hospitals (89% in 2000) to non-academic hospitals (67% in 2008). Conclusions: In hospitalized patients, off-label use of rFVIIa far exceeds use for the small number of licensed indications. Cardiac surgery, trauma, and non-traumatic intracranial hemorrhage represent the top indications for in-hospital rFVIIa use in the United States, together accounting for an estimated 12,448 of 18,311 (68%) uses during 2008. Across all off-label indications, in-hospital mortality is high, suggesting a substantial proportion of 'end-stage' use of rFVIIa. Use in such circumstances raises concerns about efficacy, associated adverse events, and allocation of resources. The marked shift in off-label use from academic to non-academic hospitals suggests wide acceptance despite these concerns. These patterns of expanding use are concerning given the absence of strong and consistent evidence to support the off-label application of rFVIIa. Disclosures: Off Label Use: This work characterizes patterns of off-label use of recombinant factor VIIa in United States hospitals..

scholarly journals Use of Factor VIIa and Anti-inhibitor Coagulant Complex in Pediatric Cardiac Surgery Patients

2020 ◽  
Vol 25 (6) ◽  
pp. 540-546
Author(s):  
Rachel B. Carroll ◽  
Hania Zaki ◽  
Courtney McCracken ◽  
Janet Figueroa ◽  
Nina A. Guzzetta
Keyword(s):  
Cardiac Surgery ◽  
Pediatric Patients ◽  
Factor Viia ◽  
Postoperative Bleeding ◽  
Pediatric Cardiac Surgery ◽  
Coagulation System ◽  
Clotting Factor ◽  
Blood Products ◽  
Excessive Bleeding ◽  
Off Label

OBJECTIVES Postoperative bleeding is a common cause of morbidity and mortality in cardiac patients who undergo cardiopulmonary bypass (CPB). Pediatric patients are especially at risk for adverse effects of surgery and CPB on the coagulation system. This can result in bleeding, transfusions, and poor outcomes. Excessive bleeding unresponsive to blood products can warrant the off-label use of recombinant activated clotting factor VIIa (rFVIIa) and/or anti-inhibitor coagulant complex (FEIBA). Several studies have shown the utility in these agents off-label in patients who have undergone cardiac bypass surgery with acute bleeding episodes that are refractory to blood products. However, data regarding use of these agents in pediatrics are sparse. The purpose of this study is to report the use of rFVIIa and FEIBA in pediatric cardiac surgery patients in our institution. METHODS This was a retrospective chart review of pediatric cardiothoracic surgery patients who received rFVIIa or FEIBA at Children's Healthcare of Atlanta during the study period. RESULTS Thirty-three patients received rFVIIa and 9 patients received FEIBA either intraoperatively or postoperatively for bleeding related to the cardiac procedure. Approximately 13% of rFVIIa patients and 55% of FEIBA patients required repeat doses. There were decreases for all blood products administered after rFVIIa and FEIBA were given. However, the doses used did not correlate with either positive or negative outcomes. Seventeen percent (n = 7) of rFVIIa patients experienced a thrombus and 22% (n = 2) of FEIBA patients experienced a thrombus. CONCLUSIONS Both rFVIIa and FEIBA reduced blood product usage in pediatric patients following cardiac procedures.

Off-Label Use of Recombinant Factor VIIA Concentrates After Cardiac Surgery

2005 ◽  
Vol 80 (1) ◽  
pp. 3-5 ◽  
Author(s):  
George Despotis ◽  
Michael Avidan ◽  
Douglas M. Lublin
Keyword(s):  
Cardiac Surgery ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

scholarly journals Evaluation of Recombinant Factor VIIa Utilization and Development of a Cost-Effective Dose Minimization Protocol in Adult Cardiac Surgery Patients at an Academic Medical Center

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5039-5039
Author(s):  
Kathryn Dane ◽  
John Lindsley ◽  
Satish Shanbhag ◽  
Michael B. Streiff ◽  
Glenn Whitman ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Low Dose ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
High Dose ◽  
Thromboembolic Events ◽  
Potential Cost ◽  
Critical Bleeding ◽  
Dosing Strategy ◽  
Adult Cardiac Surgery

Abstract Background: Although recombinant factor VIIa is often utilized to mitigate critical bleeding following cardiac surgery, the optimal dosing strategy in this population is not well-established. At our institution, hospital guidelines recommend administration of recombinant factor VIIa 60 mcg/kg for all off-label indications. However, available data suggest doses as low as 17 mcg/kg have been efficacious in cardiac surgery patients with critical bleeding. Additionally, although low-dose recombinant factor VIIa (< 40 mcg/kg) and high-dose (50-109 mcg/kg) dosing strategies have been reported equally efficacious according to retrospective, observational studies, higher doses may be associated with increased incidence of adverse events. Therefore, we aimed to evaluate the safety of recombinant factor VIIa in cardiac surgery patients with critical bleeding, and estimate potential cost-savings associated with implementation of a low-dose recombinant factor VIIa protocol in this population. Methods: All adult cardiac surgery patients who received one or more doses of recombinant factor VIIa during a 1-year period (July 1, 2016 to June 30, 2017) were included. Thromboembolic event rates documented within 14 days following recombinant factor VIIa administration were evaluated in patients alive at discharge. An average wholesale price of 2.59 USD per mcg was utilized for recombinant factor VIIa cost calculations. Results: A total of 16 patients received 24 doses of recombinant factor VIIa during the study period. The median weight-based dose administered was 55 mcg/kg (utilizing actual body weight), and the median dose was 5 mg. The median cost per recombinant factor VIIa dose was 12,950 USD, resulting in a total expenditure of 277,174 USD. Nine of sixteen patients (56%) survived to hospital discharge. Five of nine (56%) patients alive at discharge experienced thromboembolic complications following recombinant factor VIIa administration, three (60%) of which were central nervous system (CNS) thromboembolic events. Based on data supporting low-dose strategies, a proposed weight-based recombinant factor VIIa dose-minimization protocol was developed by leadership in the departments of pharmacy, hematology, cardiac surgery, and cardiac anesthesia (Table 1). Implementation of this protocol would result in an estimated annual cost-avoidance of 168,376 USD. Conclusions: Recombinant factor VIIa administration at a dose of 55 mcg/kg in adult cardiac surgery patients with critical bleeding is associated with a high rate of thromboembolic events, including CNS thromboembolism. Additionally, this recombinant factor VIIa dosing strategy is associated with significant cost, which can be substantially reduced with implementation of a low-dose recombinant factor VIIa protocol in the cardiac surgery population. Disclosures No relevant conflicts of interest to declare.

Management of Intractable Bleeding after Cardiac Surgery with Recombinant Activated Factor VII

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4526-4526
Author(s):  
Holavanahalli Keshava-Prasad ◽  
Krishna Oza ◽  
Girindra Raval ◽  
Tamim Antakli
Keyword(s):  
Cardiac Surgery ◽  
Cardiovascular Surgery ◽  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Blood Component ◽  
Blood Components ◽  
Blood Products ◽  
Before And After ◽  
Life Threatening ◽  
Delayed Closure

Abstract Background Intractable hemorrhage is a dreaded complication after cardiovascular surgery often requiring re-exploration and the administration of large quantities of blood products. In view of problems with aprotinin, a new safer effective agent is needed. Recombinant activated FVII is approved for use in patients with hemophilia A and B who have inhibitors to factors VIII and IX, and has shown promise in off-label use for the management of life-threatening hemorrhage in several clinical scenarios including cardiac surgery. It may help control bleeding, reduce blood product usage, and avoid potential morbidity. Its exact place in the management of bleeding during and after cardiac surgery is not yet fully known. Methods. We performed a retrospective review of patients who were given recombinant factor VIIa (rFVIIa; Novoseven, NovoNordisk, Copenhagen, Denmark) to control bleeding after major cardiovascular surgery requiring cardiopulmonary bypass (CPB) at our institution. The decision to administer rFVIIa was made empirically based on the observation by the surgeons of refractory bleeding that appeared unresponsive to conventional hemostasis agents including the requirement of large volumes of blood components, and was at least severe enough to prevent chest closure. We compared blood loss and blood component usage in patients before and after rFVIIa. We also performed a detailed review of the English literature to determine the role of rFVIIa in the treatment of bleeding after cardiac surgery. Results. Between August 2002 to February 2006, 1295 patients underwent open heart surgery at our institution; of these, 28 were given Novoseven either to control intractable bleeding, or to prevent major bleeding. Table 1 shows the patient characteristics. Satisfactory hemostasis was achieved in all but 3 patients after a single 90 μg/kg intravenous dose of rFVIIa. In all patients, there was a dramatic reduction in the amount of blood components (PRBCs, Platelets and FFP) used after rFVIIa infusion (Table 2). Cryoprecipitate was administered routinely with rFVIIa and its usage did not change significantly (Table 2). No thromboembolic or other complications directly related to rVIIa occurred. Conclusions. We have demonstrated that intravenous rFVIIa is effective, safe, and valuable in the management of intractable bleeding after complicated cardiac surgeries. There are several reports and reviews in the literature which corroborate our experience and indicate that recombinant factor VIIa is a potent pro-hemostatic agent which has a role in the treatment of life-threatening refractory hemorrhage associated with cardiac surgery. Earlier preemptive administration of rFVIIa during or before surgery may be of value in patients at high risk of intractable bleeding in order to limit blood loss, and to avoid potential morbidity from large volume blood component transfusions. Randomized, controlled trials are warranted to assess the efficacy, safety, and cost-benefit of this intervention in cardiac surgical patients. TABLE 1. Characteristics and operative course of the 28 patients Mean age 60 yrs (range 22–85) Male, M 24(85%); F 4(15%) Total number of surgical procedures performed: 34 Aortic valve: 7; Bentall or modified Bentall: 9 (3 emergent) Mitral Valve Replacement: 4; CABG: 10; Redo 2 Left pneumonectomy/resection of L Atrial cuff & pericardium: 1 Removal of Inferior vena cava tumor (Renal cell ca): Re-exploration: 6; Delayed closure: 5; Both re-exploration and delayed closure: Median bypass time: 214 min (65–358) Timing of Novoseven: intra op: 21 including elective use in 2 pts; post op: 7 Dose of Novoseven: 90mcg/kg in 22; 45 mcg/kg 2 patients Responders 25(89%) Outcome: Deaths 11(38%) Autopsies: 2; no evidence of systemic thrombosis Table 2. Details of the blood products administered both before and after rFVIIa infusion. Componen Mean units Before rVIIa Mean units After rVIIa Difference; p value PRBC usage 15.9 5.033333 0.045 Platelet usage 4.448276 1.37931 0.005 FFP Usage 9.931034 5.793103 0.042 Cryoppt 21.71429 12.54167 0.091

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