Activated recombinant factor VIIa should not be used in patients with refractory variceal bleeding: It is mostly ineffective, is expensive, and may rarely cause serious adverse events

SummaryBolus infusion (BI) recombinant factor VIIa (rFVIIa) administration is safe and effective in the surgical management of haemophilia patients with inhibitors but has not been compared directly with continuous infusion (CI). We conducted an open-label, randomized, multicenter trial comparing the efficacy and safety of rFVIIa administered by BI or CI for the surgical management of haemophilia A or B patients with inhibitors to FVIII or FIX. Safety was compared with that of a control group of noninhibitor patients receiving FVIII or FIX concentrates for major surgery. All inhibitor subjects received an initial bolus dose of 90 μg/kg rFVIIa and were then randomly assigned to BI (n=12) or CI (n=12). The BI group received 90 μg/kg rFVIIa every two hours (h) during surgery through day 5, then every four hours for days 6–10. The CI group received 50 μg/kg/h rFVIIa through day 5, then 25 mg/kg/h for days 6–10. The control group (n=12) received FVIII or FIX per institutional protocols. Twenty-two major surgeries included orthopedic procedures on the knee (n=13), hip (n=3), and abdominal/pelvis procedures (n=4). One patient with an autoimmune FVIII inhibitor randomized to the BI arm was excluded from efficacy analysis. Haemostatic efficacy of rFVIIa in each group was comparable: effective in 8/11 and 9/12 subjects in the BI and CI arms, respectively, and ineffective in three subjects in each arm. Serious adverse events were related to continued or increased bleeding. In conclusion, haemostatic efficacy and safety of BI and CI of rFVIIa are comparable for the surgical management of haemophilia subjects with inhibitors.

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Recombinant factor VIIa for variceal bleeding in liver cirrhosis: still only a hope

Archives of Medical Science ◽

10.5114/aoms.2017.65331 ◽

2017 ◽

Vol 2 ◽

pp. 496-499 ◽

Cited By ~ 2

Author(s):

Xingshun Qi ◽

Chun Ye ◽

Xiaozhong Guo

Keyword(s):

Liver Cirrhosis ◽

Variceal Bleeding ◽

Recombinant Factor Viia ◽

Factor Viia

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Sequential Therapy with Activated Prothrombin Complex Concentrates and Recombinant Factor VIIa in the Treatment of Unresponsive Bleeding in Patients with Hemophilia and Inhibitors

Blood ◽

10.1182/blood.v118.21.4664.4664 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4664-4664

Author(s):

Young shil Park ◽

Yong-Mook Choi ◽

Ji Kyoung Park

Keyword(s):

Adverse Events ◽

Recombinant Factor Viia ◽

Conflicts Of Interest ◽

Factor Viia ◽

Retrospective Chart Review ◽

Sequential Therapy ◽

Small Bowel Resection ◽

Prothrombin Complex Concentrates ◽

Two Agents ◽

Activated Prothrombin Complex Concentrates

Abstract Abstract 4664 The development of inhibitors to factor VIII or IX is the most common, severe, challenging and expensive complication of the treatment of patients with hemophilia. Hemophilia patients with inhibitors can develop bleeding episodes, which are refractory to monotherapy with either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (APCC). Management of such bleeds is often difficult. This report describes the results of a retrospective chart review of four hospitalized patients with severe hemophilia and inhibitors who have been treated with sequential doses of APCC and rFVIIa for refractory bleeding. Sequential therapy was defined as the administration of both rFVIIa and APCC within 12 h. In 4 cases of patients with inhibitor, bleeding was not controlled by initial bypassing treatment. One patient had historical peak inhibitor titer increased to 1126 BU, and during peripheral inserted central catheter insertion for immune tolerance induction therapy, bleeding was not controlled. After APCC and rFVIIa were administered sequentially, bleeding was controlled. The second and third patients had bleeding problem after total knee replacement for hemophilic arthropathy, and two agents were administered sequentially. The last patient had small bowel resection because of intestinal obstruction, and post-operation bleeding was not controlled well. DIC was developed. Two agents were administered sequentially for bleeding problem and bleeding was controlled. Sequential therapy administration alternated one APCC dose to 1–2 rFVIIa doses: dosing intervals ranged between 3 and 6 h; APCC (75–100 U kg) was given every 12 h; rFVIIa (90 μg/ kg) was given every 3–6 h. Bleeding control was achieved in 12–24 h in all patients. Sequential therapy was discontinued after 2–5 days. No clinical adverse events were observed. Sequential therapy with APCC and rFVIIa was efficacious without adverse events. A prospective clinical trial is needed to provide further evidence. Disclosures: No relevant conflicts of interest to declare.

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RECOMBINANT FACTOR VIIA IN TRAUMATIC INTRACEREBRAL HEMORRHAGE

Neurosurgery ◽

10.1227/01.neu.0000316898.78371.74 ◽

2008 ◽

Vol 62 (4) ◽

pp. 776-788 ◽

Cited By ~ 83

Author(s):

◽

Raj K. Narayan ◽

Andrew I.R. Maas ◽

Lawrence F. Marshall ◽

Franco Servadei ◽

...

Keyword(s):

Adverse Events ◽

Clinical Outcomes ◽

Recombinant Factor Viia ◽

Factor Viia ◽

Treated Group ◽

Dose Escalation Study ◽

Computed Tomographic ◽

Vein Thrombosis ◽

Computed Tomographic Scan ◽

Deep Vein

Abstract OBJECTIVE Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression. METHODS Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 μg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15. RESULTS No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml). CONCLUSION In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80–200 μg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.

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A Cerebrovascular Event After Single-Dose Administration of Recombinant Factor VIIa in a Patient with Esophageal Variceal Bleeding

Digestive Diseases and Sciences ◽

10.1007/s10620-005-9023-y ◽

2006 ◽

Vol 51 (9) ◽

pp. 1647-1649 ◽

Cited By ~ 5

Author(s):

Murat Akyildiz ◽

Ilker Turan ◽

Omer Ozutemiz ◽

Yucel Batur ◽

Tankut Ilter

Keyword(s):

Single Dose ◽

Variceal Bleeding ◽

Recombinant Factor Viia ◽

Factor Viia ◽

Cerebrovascular Event ◽

Esophageal Variceal ◽

Dose Administration ◽

Esophageal Variceal Bleeding ◽

Single Dose Administration

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

Therapeutic Advances in Cardiovascular Disease ◽

10.1177/1753944720924255 ◽

2020 ◽

Vol 14 ◽

pp. 175394472092425 ◽

Cited By ~ 1

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.

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