Clinical Experience with Human Plasma-Derived Factor VIla in Patients with Hemophilia A and High Titer Inhibitors

Hedner, Ulla; Bjoern, Seidel; Bernvil, S.S.; Tengborn, Lilian; Stigendahl, Lennart

doi:10.1159/000216080

Cited by 34 publications

(26 citation statements)

References 16 publications

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“…Subsequently, plasma-derived factor VIIa was observed to be effective in controlling hemorrhage in other hemophilic patients with inhibitors. 8 The difficulty in preparing factor VII from plasma resulted in a shortage of starting material that precluded extensive use of plasma-derived factor VIIa. The problem of availability was solved by the development of recombinant factor VIIa (rfVIIa) by Novo Nordisk Pharmaceuticals (Bagsvaerd, Denmark).…”

Section: Introductionmentioning

confidence: 99%

The use of recombinant factor VIIa in the treatment of bleeding disorders

Roberts

Monroe

White

2004

Blood

252

207

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Recombinant factor VIIa was initially developed for the treatment of hemorrhagic episodes in hemophilic patients with inhibitors to factors VIII and IX. After its introduction, it has also been used "off-label" to enhance hemostasis in nonhemophilic patients who experience bleeding episodes not responsive to conventional therapy. Evidence so far indicates that the use of factor VIIa in hemophilic patients with inhibitors is both safe and effective. Anecdotal reports also suggest that the product is safe and effective in controlling bleeding in nonhemophilic patients. However, its use in these conditions has not been approved by the FDA, and conclusive evidence of its effectiveness from controlled clinical trials is not yet available. Several questions pertaining to the use of factor VIIa require further investigation, including the mechanism of action; the optimal dose; definitive indications; ultimate safety; and laboratory tests for monitoring therapy. (Blood.

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Section: Introductionmentioning

confidence: 99%

The use of recombinant factor VIIa in the treatment of bleeding disorders

Roberts

Monroe

White

2004

Blood

252

207

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“…Plasma-derived FVIIa was purified from Finnish plasma bought from the Finnish Red Cross, and tested in four haemophilia patients (three with severe haemophilia A and one with haemophilia B). The results in the patients tested after approval from Health Authorities and Ethical Committees in Denmark and in Sweden were considered encouraging [26]. It became clear that developing FVIIa for clinical use should be based on gene technology to enable large scale production and to avoid transfusion transmitted infection.…”

Section: Introductionmentioning

confidence: 99%

“…In [25][26][27][28][29]1975 in Denmark (at this conference a paper by Prydz & Bjørklid on 'Structure and Function of Thromboplastin' was presented in which it was stressed that 'tissue thromboplastin triggered coagulation by forming a complex with factor VII…') my thoughts of utilizing FVIIa in clinical treatment of haemophilia were met with obvious scepticism. One argument was that haemophilia patients have normal levels of FVII, why should extra FVIIa help them?…”

Section: Introductionmentioning

confidence: 99%

Activated factor VII: my story

Hedner

2012

Haemophilia

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“…Hedner was the first to realize that FVIIa could be used as a "bypass" therapy for the treatment of patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX, which have developed either as a result of treatment of inherited hemophilia with these factors, or in patients with previously normal coagulation (acquired hemophilia), thus bypassing the need for these clotting factors [15,16,17,18]. In an in vitro system, addition of rFVIIa to FVIII-deficient plasma, to achieve a concentration similar to that after administration of an in vivo dose of 90-100 µg/kg, restores to normal the abnormal clot permeability and the fibrin network (Fig.…”

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confidence: 99%

The use of recombinant activated coagulation factor VII for spine surgery

Weiskopf

2004

Eur Spine J

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Surgery of the spine encompasses a very broad range of procedures. The extent and blood loss encountered during these procedures varies enormously (Fig. 1). A simple laminectomy or discectomy does not create much blood loss. Surgery for spinal deformity can entail blood loss of several liters. Even within this latter sub-set, the variability is great. Correction of scoliosis in an otherwise normal teenager can be associated with small-to-moderate blood loss, but is not usually associated with extensive blood loss, while correction in a child with a neuromuscular disorder, or an elderly adult frequently involves substantial blood loss. In a recent 3-year period at the University of California, San Francisco, among those patients for whom intra-operative cell salvage was used (that is, patients in whom substantial blood loss was anticipated), the range of estimated blood loss for patients undergoing spinal surgery was nil to more than 10 l (Fig. 1).When blood loss approaches or exceeds one blood volume, and replacement does not include coagulation factors, sufficient dilution of circulating coagulation factors Abstract This article focuses on our current understanding of the role of activated coagulation factor VII (FVIIa) in coagulation, the current evidence regarding the efficacy and safety of recombinant FVIIa (rFVIIa), and thoughts regarding the use of rFVIIa in spine surgery. rFVIIa is approved in many countries (including the European Union and the USA) for patients with hemophilia and inhibitors (antibodies) to coagulation factors VIII or IX. High circulating concentrations of FVIIa, achieved by exogenous administration, initiate hemostasis by combining with tissue factor at the site of injury, producing thrombin, activating platelets and coagulation factors II, IX and X, thus providing for the full thrombin burst that is essential for hemostasis. This "bypass" therapy has led some clinicians to use rFVIIa "off-label" for disorders of hemostasis other than hemophilia. Based on clinical experience, case reports and limited information from clinical trials, rFVIIa may be efficacious in states of decreased concentration of coagulation factors, thrombocytopenia, and at least some states of altered platelet function. The former two can occur intra-operatively during spinal surgery as a consequence of substantial blood loss and normal consumption. Preliminary reports have indicated that rFVIIa does not increase the perioperative incidence of thromboembolic events. However, full reports from large clinical trials regarding the efficacy and safety of rFVIIa in settings other than hemophilia have yet to appear in peer-reviewed publications. Until adequate data demonstrating safety and efficacy are fully reported, it would seem appropriate to reserve the use of rFVIIa in spinal surgery to those instances where conventional therapy cannot provide adequate hemostasis, and "rescue" therapy is required.

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Clinical Experience with Human Plasma-Derived Factor VIla in Patients with Hemophilia A and High Titer Inhibitors

Cited by 34 publications

References 16 publications

The use of recombinant factor VIIa in the treatment of bleeding disorders

The use of recombinant factor VIIa in the treatment of bleeding disorders

Activated factor VII: my story

The use of recombinant activated coagulation factor VII for spine surgery

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