Recombinant factor VIIa for the treatment of severe postoperative and traumatic hemorrhage

Khan, Atif; Parry, James M.; Crowley, William F.; McAllen, Karen; Davis, Alan T.; Bonnell, Bruce W.; Hoogeboom, James E.

doi:10.1016/j.amjsurg.2004.11.021

Cited by 34 publications

(18 citation statements)

References 6 publications

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“…Additionally, rFVIIa has been shown to inhibit fibrinolysis by activation of the thrombin activatable fibrinolysis inhibitor (TAFI) (Lisman et al, 2002). The use of rFVIIa to control bleeding has been reported in various clinical settings, including the treatment of both coagulopathic and hemostatically normal patients peri-surgically (Friederich et al, 2003;Aldouri, 2002), post-trauma (Martinowitz et al, 2001(Martinowitz et al, , 2002Kenet et al, 1999;Kamphuisen et al, 2002;O'Neill et al, 2002;Khan et al, 2005;Filsoufi et al, 2006), in liver failure (Chuansumrit et al, 2000) and in other bleeding conditions refractory to conventional therapy (Mayo et al, 2004). Of particular interest are the encouraging results to date for use of rFVIIa following spontaneous intracerebral hemorrhage (ICH) (Mayer et al, 2005a,b;Steiner et al, 2006) where rFVIIa was reported to decrease hematoma growth, reduce mortality, and improve functional outcome.…”

Section: Introductionmentioning

confidence: 99%

Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigs

Zhang¹,

Groff²,

Chen³

et al. 2008

Experimental Neurology

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Human recombinant activated factor-VII (rFVIIa) has been used successfully in the treatment of spontaneous intracerebral hemorrhage. In addition, there is increasing interest in its use to treat uncontrolled bleeding of other origins, including trauma. The aim of this study was to evaluate the safety and potential effectiveness of rFVIIa to mitigate bleeding using a clinically relevant model of traumatic brain injury (TBI) in the pig. A double injury model was chosen consisting of (1) an expanding cerebral contusion induced by the application of negative pressure to the exposed cortical surface and (2) a rapid rotational acceleration of the head to induce diffuse axonal injury (DAI). Injuries were performed on 10 anesthetized pigs. Five minutes after injury, 720 μg/kg rFVIIa (n = 5) or vehicle control (n = 5) was administered intravenously. Magnetic resonance imaging (MRI) studies were performed within 30 min and at 3 days post-TBI to determine the temporal expansion of the cerebral contusion. Euthanasia and histopathologic analysis were performed at day 3. This included observations for hippocampal neuronal degeneration, axonal pathology and microclot formation. The expansion of contusion volume over the 3 days postinjury period was reduced significantly in animals treated with rFVIIa compared to vehicle controls. Surprisingly, immunohistochemical analysis demonstrated that the number of dead/dying hippocampal neurons and axonal pathology was reduced substantially by rFVIIa treatment compared to vehicle. In addition, there was no difference in the extent of microthrombi between groups. rFVIIa treatment after TBI in the pig reduced expansion of hemorrhagic cerebral contusion volume without exacerbating the severity of microclot formation. Finally, rFVIIa treatment provided a surprising neuroprotective effect by reducing hippocampal neuron degeneration as well as the extent of DAI.

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Section: Introductionmentioning

confidence: 99%

Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigs

Zhang¹,

Groff²,

Chen³

et al. 2008

Experimental Neurology

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“…Almost all reports have demonstrated remarkable efficacy as a haemostatic agent [9]. A local action at the site of injury is produced by binding of the recombinant factor VIIa to exposed tissue factor enhancing production of thrombin and activation of platelets to mediate further activation of the coagulation cascade, but other mechanisms for the potent action of this agent have also been proposed [1].…”

Section: Discussionmentioning

confidence: 99%

Recombinant activated factor VII to control life-threatening haemorrhagic radiation cystitis

2009

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“…The first report of using rFVIIa as an off-label therapy for trauma in adults was in 1999 [3], and since then, there have been an increasing number of articles reporting on its use in traumatic injuries [4][5][6][7][8][9][10]. A multicenter, prospective, randomized trial compared the effects of rFVIIa with placebo in trauma patients [9].…”

Section: Discussionmentioning

confidence: 99%

“…Typically, these treatments include angioembolization techniques in interventional radiology [2] or operative control of the bleeding. Recently, a hemostatic agent known as recombinant activated factor VII (rFVIIa) has been used as a noninvasive therapy for continued bleeding in the adult trauma literature [3][4][5][6][7][8][9][10] and has only been seen in a few cases of pediatric trauma [11,12].…”

mentioning

confidence: 99%

Recombinant factor VIIa as an adjunct in nonoperative management of solid organ injuries in children

Vick

Islam

2008

Journal of Pediatric Surgery

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Recombinant factor VIIa for the treatment of severe postoperative and traumatic hemorrhage

Cited by 34 publications

References 6 publications

Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigs

Hemostatic and neuroprotective effects of human recombinant activated factor VII therapy after traumatic brain injury in pigs

Recombinant activated factor VII to control life-threatening haemorrhagic radiation cystitis

Recombinant factor VIIa as an adjunct in nonoperative management of solid organ injuries in children

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