Challenges in the Therapeutic Use of a “So-Called” Universal Hemostatic Agent: Recombinant Factor VIIa

Hoots, W. Keith

doi:10.1182/asheducation-2006.1.426

Cited by 18 publications

(13 citation statements)

References 41 publications

(46 reference statements)

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“…Decisions regarding dose are particularly relevant to the risk arterial thrombotic complications that appear to be dose dependent (28). In patients with intact mechanisms of thrombin generation, higher rFVIIa doses may augment thrombin production distant to the site of bleeding in a tissue factor-independent manner, resulting in thromboembolic complications without improved hemostatic effects (47). In vitro data suggests that a low dose of rFVIIa (equivalent to 20 μg/kg) has similar efficacy to higher doses (100 – 200 μg/kg) as measured by thrombin generation (48).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Factor VIIa for Alveolar Hemorrhage Following Allogeneic Stem Cell Transplantation

Elinoff

Bağcı

Moriyama

et al. 2014

Biology of Blood and Marrow Transplantation

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The mortality rate of alveolar hemorrhage following allogeneic hematopoietic stem cell transplantation is greater than 60% with supportive care and high dose steroids. We performed a retrospective cohort analysis to assess the benefits and risks of rFVIIa as a therapeutic adjunct for alveolar hemorrhage. From 2005 to 2012, 57 episodes of alveolar hemorrhage occurred in 37 patients. Fourteen episodes (in 14 patients) were treated with steroids alone and 43 episodes (in 23 patients) were treated with steroids and rFVIIa. The median (interquartile range) steroid dose was 1.9 mg/kg/d (0.8 – 3.5; methylprednisolone equivalents) and did not differ statistically between the two groups. The median rFVIIa dose was 41 μg/kg (39-62) and a median of 3 doses (2-17) was administered per episode. Concurrent infection was diagnosed in 65% of the episodes. Patients had moderately severe hypoxia (median PaO2/FiO2, 193 [141-262]); 72% required mechanical ventilation and 42% survived to extubation. The addition of rFVIIa did not alter time to resolution of alveolar hemorrhage (p = 0.50), duration of mechanical ventilation (p = 0.89), duration of oxygen supplementation (p = 0.55), or hospital mortality (p = 0.27). Four possible thrombotic events (9% of 43 episodes) occurred with rFVIIa. rFVIIa when used in combination with corticosteroids did not confer clear clinical advantages compared to corticosteroids alone. In patients with AH following hematopoietic stem cell transplant, clinical factors (i.e. worsening infection, multiple organ failure or recrudescence of primary disease) may be more important than the benefit of enhanced hemostasis from rFVIIa.

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Factor VIIa for Alveolar Hemorrhage Following Allogeneic Stem Cell Transplantation

Elinoff

Bağcı

Moriyama

et al. 2014

Biology of Blood and Marrow Transplantation

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“…Where a specific factor replacement is not available, fresh-frozen plasma (FFP) and/or cryoprecipitate may be used (table 1d). Recombinant FVIIa has been suggested as a universal hemostatic agent [26]. This approach is not without challenges and preference should always be given to a specific replacement therapy, when available.…”

Section: Congenital Coagulopathiesmentioning

confidence: 99%

Hematological Problems in Pediatric Intensive Care

Revel‐Vilk

Cox²,

Robitaille

et al. 2013

Controversies in Pediatric and Adolescent Hematology

2,581

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Hematologic abnormalities are common in children admitted to pediatric intensive care units (PICUs). Some are primary and related to the underlying hematologic disease in the child such as severe anemia in a young child with sickle cell disease and an acute splenic sequestration crisis. Others are secondary to other underlying conditions such as disseminated intravascular coagulation secondary to sepsis. Perhaps the most common association is with surgery or following trauma. The approach to the diagnosis and management of hematologic disorders in children cared for in PICUs requires an appreciation of disorders, some very rare, where delays in diagnosis and initiation of effective treatment can be associated with significant morbidity/mortality (e.g. thrombotic thrombocytopenic purpura, hemophagocytic lymphohistiocytosis) as well as more 'mundane' but equally important decisions such as transfusion triggers for replacement of packed red blood cells, freshfrozen plasma, cryoprecipitate or platelets. In all situations, a best practice approach based on available published evidence and expert opinion is recommended. In large tertiary/quaternary care centers, a close working relationship between the pediatric intensivist staff and the clinical/laboratory hematology services is essential for optimizing the care of critically ill children with hematologic problems cared for in PICUs.A wide range of hematologic problems occur in patients admitted to pediatric intensive care units (PICUs). These may reflect primary hematologic disorders or arise as complications of other underlying conditions. The aim of this chapter is to focus on hematologic disorders seen in children aged >4 months to <18 years of age

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“…This is followed by platelet aggregation by means of docking proteins or sites to form the primary hemostatic clot. The sequence of platelet aggregation is mediated by von Willebrand factor, which forms links between the platelet GP Ib/IX/V and collagen [54–56]. Once they bind and are thereby activated, platelets undergo structural and conformational changes and begin platelet-platelet aggregation via the GP IIb/IIIa receptors.…”

Section: Inflammatory Reactions and Vascular Damage Coagulation Factorsmentioning

confidence: 99%

“…Following damage to the blood vessel, Endothelium Tissue Factor (ETF) is released, forming a complex with Factor VIIa, which then activates Factor IX and X. Factor VII is a coagulation factor in the extrinsic coagulation pathway and is part of a series of hemostatic defense mechanisms [55,56]. Factor VII itself can also be activated by thrombin leading to a cyclic complex including the activation of prothrombin to thrombin.…”

Section: Inflammatory Reactions and Vascular Damage Coagulation Factorsmentioning

confidence: 99%

Vascular Dysfunction in Brain Hemorrhage: Translational Pathways to Developing New Treatments from Old Targets

Lapchak¹,

Wu²

2011

J Neurol Neurophysiol

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Hemorrhagic stroke which is a form of stroke that affects 20% of all stroke patients is a devastating condition for which new treatments must be developed. Current treatment methods are quite insufficient to reduce long term morbidity and high mortality rate, up to 50%, associated with bleeding into critical brain structures, into ventricular spaces and within the subarachnoid space. During the last 10–15 years, significant advances in the understanding of important mechanisms that contribute to cell death and clinical deficits have been made. The most important observations revolve around a key set of basic mechanisms that are altered in brain bleeding models, including activation of membrane metalloproteinases, oxidative stress and both inflammatory and coagulation pathways. Moreover, it is now becoming apparent that brain hemorrhage can activate the ischemic stroke cascade in neurons, glial cells and the vascular compartment. The activation of multiple pathways allows comes the opportunity to intervene pharmacologically using monotherapy or combination therapy. Ultimately, combination therapy or pleiotropic compounds with multi-target activities should prove to be more efficacious than any single therapy alone. This article provides a comprehensive look at possible targets for small molecule intervention as well as some new approaches that result in metabolic down-regulation or inhibition of multiple pathways simultaneously.

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Challenges in the Therapeutic Use of a “So-Called” Universal Hemostatic Agent: Recombinant Factor VIIa

Cited by 18 publications

References 41 publications

Recombinant Human Factor VIIa for Alveolar Hemorrhage Following Allogeneic Stem Cell Transplantation

Recombinant Human Factor VIIa for Alveolar Hemorrhage Following Allogeneic Stem Cell Transplantation

Hematological Problems in Pediatric Intensive Care

Vascular Dysfunction in Brain Hemorrhage: Translational Pathways to Developing New Treatments from Old Targets

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