Evidence for the Use of Recombinant Factor VIIa in the Prevention and Treatment of Bleeding in Patients Without Hemophilia

Birchall, Janet; Stanworth, Simon; Duffy, Michael; Dorée, Carolyn; Hyde, Christopher

doi:10.1016/j.tmrv.2008.02.007

Cited by 22 publications

(8 citation statements)

References 49 publications

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“…Patients included in RCTs are generally highly selected and thus may not represent the general population with respect to risk for thromboembolic complications from rFVIIa therapy (eg, individuals with a history of venous or arterial thromboembolism are most commonly excluded from rFVIIa trial enrollment). 36 In several of the previously mentioned trials, the occurrence of TAEs was noted, although given the small size of most trials, these events were generally not prevalent in high enough numbers to reach statistical significance.…”

Section: Rfviia Use In Spontaneous Ichmentioning

confidence: 93%

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

Logan

Goodnough

2010

Hematology

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Recombinant human factor VIIa (rFVIIa) is approved by the US Food and Drug Administration for use in the setting of hemorrhage associated with factor VIII or factor IX inhibitors in patients with congenital or acquired hemophilia. This indication represents only a small number of bleeding conditions. Since it became available, rFVIIa has been increasingly used in the management of off-label indications, ranging from emergent hemostasis in traumatic hemorrhage to prophylactic hemostasis in patients undergoing major surgery. Prominent off-label indications include the management of patients with coagulopathies, such as occurs in trauma patients experiencing massive and uncontrolled hemorrhage, and in patients undergoing cardiovascular surgery with cardiopulmonary bypass. Other occasions for use occur in patients with intact coagulation systems, with nontraumatic intracranial hemorrhage being the most common in this group. Uncertainties regarding the efficacy and safety associated with use of rFVIIa in these off-label scenarios have led to evidence-based assessments of patient outcomes, including mortality, the rate of thromboembolic adverse events, and posttreatment functional status. We review the evidence regarding the efficacy and safety of this important, but controversial, hemostatic agent in the off-label setting.

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Section: Rfviia Use In Spontaneous Ichmentioning

confidence: 93%

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

Logan

Goodnough

2010

Hematology

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“…These events occurred despite the exclusion of patients with a previous history of thromboembolic disease. The most serious thromboembolic events (myocardial infarction and ischaemic stroke) were only reported in patients receiving FVIIa in these studies (none were reported in placebo groups) 31. Mayer et al 32 showed a similar frequency of thromboembolic events in each of their cohorts studied during intracranial haemorrhage but arterial thromboembolism was significantly more common in the higher-dose treatment arm than placebo (9% vs 4%; p=0.04).…”

Section: Pharmaceutical Treatmentsmentioning

confidence: 86%

“…In recent years unlicensed use of factor VIIa has increased dramatically and it has been incorporated in many hospitals' guidelines for major haemorrhage, even though the evidence for its use in this setting is poor. A recent systematic review assessed 17 randomised controlled trials undertaken using VIIa 31. These included studies of prophylactic use to prevent bleeding in haemorrhage-prone routine surgery, emergency treatment of ongoing haemorrhage and lastly, treatment of early intracranial haemorrhage.…”

Section: Pharmaceutical Treatmentsmentioning

confidence: 99%

Management of acquired coagulopathy in acute paediatrics

Morley

2010

Archives of Disease in Childhood - Education and Practice

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Acquired coagulopathy is a relatively uncommon occurrence in acute paediatrics but when it occurs is usually associated with significant underlying pathology and often with critical illness. It can be caused by a number of disease processes but infection, blood loss, iatrogenic causes and liver dysfunction are among the commonest. The blood coagulation cascade is complex and intersects with many other physiological pathways. It is also subject to developmental changes, and 'normal' coagulation and haemostasis change considerably during early life. The diagnosis of abnormal coagulation and when treatment should be initiated is influenced both by age and developmental status and limited by the range of tests routinely available to clinicians. Treatment has predominantly involved transfusion of plasma products (usually fresh frozen plasma and cryoprecipitate) but a number of pharmaceutical and human-derived options are now available. Although plasma products are less frequently transfused than red cells or platelets, their use continues to increase and has not followed the reducing usage of other blood components. This article discusses the aetiology of coagulopathy, describes the commonly available diagnostic tests and outlines the evidence available to guide paediatricians when treating acutely ill children with acquired coagulopathy.

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“…We are able to provide indication-specific findings for disparate clinical applications, as well as an overview of use that identifies outcome patterns across indications, such as an increase in thromboembolism for some. Prior reviews that pooled data for multiple indications identified no mortality benefit with off-label rFVIIa use (2, 95–100) and several noted a nonsignificant increase in thromboembolism (2, 96) (98–100) or, more recently, a significant increase(5), but none could provide indication-specific guidance. Regarding specific indications, a Cochrane review of ICH and hemostatic drug therapies, overwhelmingly rFVIIa, noted no mortality reduction but a nonsignificant increase in thromboembolism (3), while a more recent review by Yuan and colleagues had the same findings as ours regarding a significantly increased risk of arterial thromboembolism without any attendant benefits for mortality or functional outcome(101).…”

Section: Discussionmentioning

confidence: 99%

Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications

Tuohy²,

et al. 2011

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Background Recombinant Factor VIIa (rFVIIa), a hemostatic agent approved for hemophilia, is increasingly used for off-label indications. Purpose To evaluate benefits and harms of rFVIIa use for five off-label, in-hospital indications: intracranial hemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy. Data Sources Ten databases (including PubMed, EMBASE, and Cochrane Library) queried from the advent of each through December 2010. English language articles were analyzed. Study Selection Two reviewers independently screened titles and abstracts to identify clinical use of rFVIIa for the selected indications and identified all randomized controlled trials (RCTs) and observational studies for full-text review. Data Extraction Two reviewers independently assessed study characteristics and rated study quality and indication-wide strength of evidence. Data Synthesis Inclusion criteria were met by 17 RCTs, 33 comparative observational studies, and 23 non-comparative observational studies. Identified comparators were limited to placebo (RCTs) or usual care (observational studies). For intracerebral hemorrhage, mortality was not improved with FVIIa use across a range of rFVIIa doses. Arterial thromboembolism was increased with rFVIIa for medium-dose (risk difference 0.03 [0.01, 0.06]) and high-dose use (0.06 [0.01, 0.11]). For adult cardiac surgery, there was no mortality difference, but an increased risk of thromboembolism (0.05 [0.01, 0.10]) with rFVIIa. For body trauma, there were no differences in mortality or thromboembolism, but a reduced risk of acute respiratory distress syndrome (−0.05 [−0.02, −0.08]). Mortality and thromboembolism were consistently higher in observational studies compared to RCTs. Limitations The amount and strength of evidence was low for the majority of outcomes and indications. Publication bias could not be excluded. Conclusion Limited available evidence for five off-label indications indicates no mortality reduction with rFVIIa use. For some indications, rFVIIa increases thromboembolism. Primary Funding Source Agency for Healthcare Research and Quality

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Evidence for the Use of Recombinant Factor VIIa in the Prevention and Treatment of Bleeding in Patients Without Hemophilia

Cited by 22 publications

References 49 publications

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

Recombinant Factor VIIa: An Assessment of Evidence Regarding Its Efficacy and Safety in the Off-Label Setting

Management of acquired coagulopathy in acute paediatrics

Systematic Review: Benefits and Harms of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications

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