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Reports describing symptoms and treatment of patients with congenital factor VII (FVII) deficiency frequently relate to patients in Europe, while only a small number describe data from Asian countries.This multicenter, prospective observational study (NCT01312636) collected data from 30 sites for 55% of patients registered in 2011 in Japan with congenital FVII deficiency treated with activated recombinant FVII (rFVIIa) for bleeding episodes and/or during surgery.The mean follow-up in 20 eligible patients was 11 months (range 1-49 months). Of 348 bleeding episodes in seven patients, 170 (48.9%) were intra-articular bleeding and 62 (17.8%) were menorrhagia, of which 92.9% (158/170) and 100% (62/62) were in patients with baseline factor VII activity 20 IU/dl or less, respectively. The hemostatic effect after rFVIIa treatment was rated as excellent, effective or partially effective for 45.7, 33.6 and 18.4% of 348 bleeding episodes. Overall, hemostasis for bleeding events and surgery was achieved in nearly 2 days, with the majority of patients receiving two doses or less. The hemostatic effect after the recommended dose (15-30 μg/kg) of rFVIIa was rapid and effective treatment for all categories of bleeding and surgical procedure.On the basis of data from routine clinical practice, no new safety signals were identified., Trial Registration: NCT01312636., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

In cardiac surgery, supplementation with recombinant factor VIIa is the treatment of choice for patients with factor VII deficiency, but overzealous administration can be associated with thromboembolic side-effects. A 53-year-old man with factor VII activity 15.2%, international normalized ratio 2.9, and acute thrombotic critical coronary anatomy, underwent coronary artery bypass surgery and a thoracotomy with decortication 5 months later. He was managed successfully without recombinant factor VIIa supplementation. This case demonstrates that current bedside and laboratory tests such as thromboelastography, prothrombin time or international normalized ratio, and factor VII activity may not predict replacement therapy in these patients.

Background: Acquired factor VII (FVII) deficiency with inhibitor increases the risk of hemorrhage during pregnancy. However, there are no published reports guiding its management in the peripartum period., Case: A 24-year-old woman with inhibitory antibodies to FVII delivered at 34 weeks of gestation. The patient was administered recombinant factor VIIa (rFVIIa) and tranexamic acid. There were no bleeding-related complications; however, the FVII level was supratherapeutic. The patient returned during a second pregnancy. A reduced dose of rFVIIa was administered. The delivery was complicated by postpartum hemorrhage, which resolved with the addition of uterotonic agents., Conclusion: Recombinant FVIIa and tranexamic acid offer an effective peripartum treatment in women with inhibitory antibody to FVII. Further research should delineate the optimal time of administration., (Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

The use of recombinant FVIIa (rFVIIa) to control bleed in individuals with FVII deficiency has been proven to be effective. The main problems associated with its use are that it requires frequent bolus injections to counteract its short half-life and high cost. Our study aimed to evaluate whether any advantage could be gained by providing rFVIIa by continuous infusion during surgery with regard to haemostatic efficacy, safety and cost. The prospective study included 10 patients with severe FVII deficiency, who underwent 25 surgical procedures (13 major and 12 minor procedures) and were treated with rFVIIa administered by continuous infusion. Tranexamic acid was given concomitantly every 8 h. Prothrombin time, FVII:C assay and thrombin generation assay were used to monitor the treatment. The mean total dose given was 10 mg during a major surgery and 4.4 mg during a minor surgery for a mean treatment duration of 7.5 and 4.0 days respectively. This corresponds to a reduction of 70-90% in drug usage and medication cost compared with bolus injections. Except for one major perioperative bleeding, excellent haemostasis was achieved in all procedures. One patient developed a transient inhibitory activity. None of these events affected the postoperative course or prolonged the hospital stay. Our study demonstrated that continuous infusion of rFVIIa during surgery is safe, effective and highly cost effective., (© 2011 Blackwell Publishing Ltd.)

Inherited factor VII (FVII) deficiency is a rare autosomal-recessive bleeding disorder. There are no clear guidelines regarding therapy in such patients when intracerebral surgery is performed. We report the use of recombinant activated FVII (rFVIIa) for the prophylaxis of bleeding in a female with FVII deficiency (8% of activity) undergoing urgent removal of a right fronto-rolandic intracerebral haematoma secondary to a bleeding from a cavernous angioma. To assist haemostasis during and after surgery, rFVIIa boluses were administered during the procedure and continued every 12 h during 3 days after operation to maintain a prothrombin time <15 s. Using this approach, no abnormal bleeding or thromboembolic complications were observed and rFVIIa appeared safe in this context.

Recombinant activated factor VII (rFVIIa) has been used in the treatment of various congenital and acquired hemostatic disorders for more than 10 years. Hemostasis is initiated by the FVIIa bound to tissue factor (TF), which constitutes only approximately 1% of total amount of the FVII protein existing in the blood. rFVII becomes activated only after the binding to the TF, released at the site of tissue injury. The efficiency of rFVIIa in the treatment of such life-threatening hemorrhagic states like hemophilia reaches up to 76-84%. rFVIIa is successfully used in the treatment of congenital deficiency of factor VII. It normalizes prothrombin time in the patients with the liver diseases and in cases of overdose of indirect anticoagulants. It is also useful for patients suffering from thrombocytopenia, thrombocyte function disorders, hemophilia A and B with development of inhibitors. rFVIIa allows overcoming uncontrollable hemorrhages, etc. It is supposed that rFVIIa is becoming a universal hemostatic drug.

Recombinant activated coagulation factor VII (rFVIIa) was developed for the treatment of patients with hemophilia who have developed inhibitors against the factor they are missing. Hemophilia is a serious bleeding disorder and patients with hemophilia develop repeated spontaneous CNS, joint and muscle bleeding. Any trauma, even mild events, may cause life-threatening bleeding, and without treatment, these patients have a life expectancy of about 16 years. Thus, hemophilia can be regarded as a model of severe bleeding, and an agent capable of inducing hemostasis in severe hemophilia independent of the hemophilia proteins (FVIII or FIX) may also be effective in patients without hemophilia who experience serious bleeds. The availability of rFVIIa stimulated research on the role of FVII and tissue factor (TF) in the hemostatic process. As a result, a picture partly different from the one suggested by previous models has emerged. These previous models basically neglected the role of cells and cell membranes. The importance of platelets and platelet membrane phospholipids in hemostasis has been demonstrated, and the new concept of the hemostatic process, focusing on cell surfaces, has been outlined.

Recombinant activated factor VII (rFVIIa) is a novel hemostatic agent, originally developed for the treatment of hemorrhage in hemophiliacs with inhibitors, which has been successfully used recently in an increasing number of nonhemophilic bleeding conditions. In the present systematic review we report the existing literature data on the use of this hemostatic agent in severe bleeding, unresponsive to standard treatment, associated with disseminated intravascular coagulation. A total of 99 disseminated intravascular coagulation-associated bleeding episodes treated with rFVIIa were collected from 27 published articles: in the majority of the cases, the underlying disorder complicated by disseminated intravascular coagulation was a postpartum hemorrhage, while in the remaining cases it was a cancer, trauma, sepsis or liver failure. Although limited, the data available suggest that rFVIIa could have a potential role in this clinical setting. Large randomized trials are needed, however, to confirm the preliminary results and to assess the safety and dosing regimens of this agent in refractory bleeding associated with disseminated intravascular coagulation.

Recombinant-activated factor VII (rFVIIa) represents a therapeutic advance for the treatment and prevention of haemorrhage in patients with the rare bleeding disorder, congenital FVII deficiency. Thirty-nine cases of the use of rFVIIa in 30 patients with congenital FVII deficiency were identified from the international, internet-based registry haemostasis.com, which is a repository of case reports on the investigational use of rFVIIa that have been voluntarily submitted by physicians worldwide. These registry data have limitations compared with clinical-trial data but give valuable insights into a treatment for a rare disease that is virtually impossible to assess in conventional clinical trials. rFVIIa was used in: elective surgery (13 cases); haematoma (9 cases); emergency surgery (6 cases); epistaxis (4 cases); menorrhagia (2 cases); cover during childbirth (2 cases); disseminated intravascular coagulation (1 case; premature infant); removal of intradermal stitches (1 case); and haematuria (1 case). In 22/39 cases, rFVIIa was used prophylactically. Total dose and dosing schedules varied; median individual dose was 13.3 mug/kg body weight (bw) (range 1.2-223.8 mug/kg bw), median total dose was 38 microg/kg bw (range 1.2-758 microg/kg bw) and median number of doses was 3 (range 1-55). rFVIIa was generally associated with bleeding cessation or markedly reduced bleeding. Two adverse events were reported, but neither was regarded as being related to rFVIIa. These 39 cases support data confirming the safety and efficacy of rFVIIa in its EU-licensed indications, including that for preventing and/or controlling haemorrhage in patients with congenital FVII deficiency.

The administration of recombinant activated factor VII (rFVIIa) by continuous infusion has provided a safe and convenient alternative to bolus injections in haemophiliacs with inhibitors, but it has only been reported in a single case with congenital factor VII (FVII) deficiency. The results of 12 consecutive surgical procedures in 7 patients with congenital FVII deficiency are reported here. rFVIIa was always given in continuous infusion,aiming at plasma FVII activity of 0.5 IU/mL. Treatment was given for 2 to 7 days with a mean total dose of 7.8 mg rFVIIa. Blood loss was as expected from the different types of procedures and the only thromboembolic complication was a superficial thrombophlebitis at the infusion site. This mode of substitution was therefore safe, effective and well tolerated.

Recombinant Factor VIIa (rVIIa) is a potent hemostatic agent for the management of refractory bleeding in patients with Factor VII deficiency or Factor VIII inhibitors. While the current recommended dose is usually effective, the most appropriate dose remains a subject of debate. Since factor VII levels and shortening of the pro-thrombin time do not appear to correlate with response, an appropriate laboratory marker of clinical response has not been identified. In this article we report changes noted in thrombin generation, platelet function and clot structure in blood from patients treated with rVIIa. Thrombin generation was assessed via a thrombin generation time (TGT) assay using a Hemodyne HAS instrument. Changes in clot structure were assessed as changes in clot elastic modulus in the HAS, changes in maximum amplitude in the TEG and changes in maximum clot firmness in the ROTEG. The cases presented confirmed improvement in thrombin generation with administration of rVIIa. The cases also illustrate that: a) in the factor VII deficient patient, 25% of the 90 microg/kg dose is sufficient to totally correct the defect, b) patients with high level factor VIII inhibitors may require significantly more than the recommended dose of 90 microg/kg, c) thrombin generation may not be completely corrected despite dramatic shortening of the prothrombin time, and d) increasing rVIIa doses does not by itself ensure improved thrombin generation.

Purpose: Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings., Source: A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage., Principal Findings: Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro., Conclusions: Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.

The authors report two cases of successful employment of human recombinant activated factor VII in gynecological oncological patients (endometrial cancer and vaginal sarcoma) without pre-existing coagulopathy. They conclude that recombinant factor VIIa may be an important and effective drug in severe bleeding in gynecological oncology.

Haemostasis is initiated by the complex formed by tissue factor (TF) and activated factor VII (FVIIa) present in the blood [1% of the factor VII (FVII) protein]. Recombinant FVIIa (rFVIIa), enzymatically active only after complex formation with TF exposed following tissue damage, has been demonstrated to induce haemostasis in haemophilia patients with life- and limb-threatening bleedings with an efficacy rate of 76-84% in patients having failed on other treatment. rFVIIa has been successfully used in patients with congenital FVII deficiency and has been demonstrated to normalize the prolonged prothrombin time in patients with liver disease and in warfarin-treated individuals. In patients with thrombocytopenia, rFVIIa shortened the prolonged bleeding time in 50% of the patients treated and a haemostatic effect on acute bleeds in eight patients was demonstrated. One patient with Glanzmann's thrombasthenia and three with Type III von Willebrand's disease were successfully treated with rFVIIa. By exploiting the binding capacity of FVIIa to platelets, rFVIIa, may also be used to enhance normal haemostasis in patients without coagulation defects but suffering from bleedings in organs or at sites with limited possibilities for mechanical haemostasis.