Immunological Aspects of Recombinant Factor Vila (rFVIIa) in Clinical Use

Nicolaisen, Else Marie; Hansen, Lisbeth Lyng; Poulsen, F. Reibke; Glazer, Steven; Hedner, Ulla

doi:10.1055/s-0038-1650554

Cited by 38 publications

(33 citation statements)

References 1 publication

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“…Anecdotal reports of inhibitors to FVII have been previously published in the literature, including reports from members of our group (Nicolaisen et al, 1996;Mariani et al, 1999;Ingerslev et al, 2005;Pruthi et al, 2007, Batorova et al, 2007Tokgoz et al, 2012). Here, we report a prospective study in which screening for FVII antibodies was performed according to a specific protocol within the frame of the Seven Treatment Evaluation Registry (STER), which also collected data on the treatment of spontaneous bleeding episodes, surgical interventions and prophylaxis in patients with congenital FVII deficiency over an 8-year period (Mariani et al, 2011;Mariani et al, 2012b;Mariani et al, 2013;Napolitano et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Inhibitors to factor VII in congenital factor VII deficiency

et al. 2014

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Running title: FVII inhibitors in congenital FVII deficiency: the STER [55 characters; maximum 60 characters and spaces]2 SummaryCongenital factor VII (FVII) deficiency is a rare bleeding disorder, and few anecdotal reports are available regarding FVII inhibitors. Using data from the Seven Treatment Evaluation Registry (STER; 225 patients, 312 treatments), we have prospectively evaluated the occurrence of FVII inhibitors using a standardized method over a period of 8 years. The central laboratory screened 115 paired samples; FVII inhibitors were detected in 3/115 (2.6%) patients (one de novo inhibitor and two pre-existing inhibitors). A fourth inhibitor was detected in a patient who had been screened locally. All four patients had high-responding inhibitors (10-72 BU) and had previously received factor replacement therapy. In three patients, the inhibitors appeared before the age of 6 months during prophylaxis following central nervous system or gastrointestinal bleeds; however, treatments were continued without apparent loss of efficacy. In one patient, an inhibitor developed in adulthood after replacement therapy for minor surgery. No anaphylactoid reactions or renal complications were reported during or after prophylaxis. In conclusion, inhibitor development is rare in patients with congenital FVII deficiency (2%), with an incidence similar to that in patients with haemophilia B. FVII inhibitors display immunological (anamnesis) and kinetic features similar to those in patients with haemophilia. Summary word count: 198 words (maximum 200 words)

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Section: Introductionmentioning

confidence: 99%

Inhibitors to factor VII in congenital factor VII deficiency

et al. 2014

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“…For the actual treatment of bleeding episodes, the main therapeutic approaches are large doses of human factor VIII (FVIII), FVIII derived from porcine plasma and products that bypass the coagulation defect, such as prothrombin complex concentrates (PCCs), activated prothrombin complex concentrates (aPCCs), [11][12][13][14] and recombinant activated factor VII (rFVIIa). [15][16][17][18][19] The introduction and availability of these products in treatment have contributed to prolonging patients' life expectancy and to improving their quality of life. 20 On the other hand, the management of hemophilia with inhibitors is particularly expensive, both in absolute terms and in comparison with the treatment of hemophilia without inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group

Gringeri

Mantovani

Scalone

et al. 2003

Blood

340

358

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Inhibitors in patients with hemophilia are a rare complication of a rare disease causing pain and disability in patients and impairment to the quality of their lives. Recent advances in treatment have brought improvements, but they have done so by absorbing larger amounts of financial resources. This study involved 52 Italian patients with hemophilia with high-responding inhibitors who were longitudinally observed for 18 months to evaluate concomitantly cost of care and quality of life. Overall, 0.6 bleeding episodes per patient per month were recorded. This frequency of events was lower than that reported in other cohorts of patients with hemophilia who were not taking inhibitors. The average monthly cost of care was, in euros, €18 000 (US $18 000) per patient, mainly because of treatment products. Recombinant activated factor VII, mostly used for orthopedic surgery, represented 50% of the expenses. Quality of life, measured through validated questionnaires, was similar to that of patients with severe hemophilia without inhibitors. In particular, physical quality of life was similar to that in patients with diabetes and on dialysis, whereas mental quality of life was comparable to that in the general population. This study shows that hemophilia complicated by inhibitors, a prototype of rare disease, requires high amounts of resources for management that provides a satisfactory quality of life. (Blood. 2003;

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“…Firstly, we used a previously described ELISA method in which patient plasma was screened for the presence of anti-FVII(a) IgG. 17 Reference ranges and cut-off limits were established by screening multiple normal donors. Secondly, in order to screen for a neutralizing antibody to FVII, we used a plasma mixing assay.…”

Section: Fvii Antibody Screening Methodsmentioning

confidence: 99%

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients

Toor

Slungaard

Hedner

et al. 2002

Bone Marrow Transplant

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Summary:Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.

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Immunological Aspects of Recombinant Factor Vila (rFVIIa) in Clinical Use

Cited by 38 publications

References 1 publication

Inhibitors to factor VII in congenital factor VII deficiency

Inhibitors to factor VII in congenital factor VII deficiency

Cost of care and quality of life for patients with hemophilia complicated by inhibitors: the COCIS Study Group

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients

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