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The diagnostic and therapeutic approach for an unusual clinical situation is presented. Twenty-three-year-old female patient is evaluated for hematuria and metrorrhagia. She reported irregular follow-up with hematology because of bleeding in childhood. She has also been receiving factor VII for 2 years, denying hospitalizations because of bleeding. Laboratory reported hb: 5.2 g/dl; platelets: 234 000/mm 3 ; PT: 100 s; PTT: 112 s, fibrinogen: 90 mg/dl without other alterations. Abdominal ultrasound reported uterine myoma, urinalysis was pathological. The gynecology indicated oral progesterone. She started antibiotic therapy, transfusion of red-blood cells, plasma, and cryoprecipitates and subsequently reported: factor VII: 2%, IX: 1% and VIII: 70%. She received factor VII-recombinant (rFVII), achieving resolution of bleeding. She was prescribed prophylactic rFVII and hematology monitoring. Readmission due to acute abdomen with Hb 5 g/dl, prolonged prothrombin time (PT)/partial thromboplastin time (PTT) and abdominal tomography reported hemoperitoneum. She received rFVII and required laparotomy and left oophorectomy. Then readmission to metrorrhagia, hb6 g/dl, prolonged PT/PTT and factor VII-IX of two coagulation factors were reported, without reports found in the literature consulted., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

Introduction: Inherited factor VII (FVII) deficiency (FVIID) is the most common of inherited rare bleeding disorders. Other determinants of clinical severity apart from FVII level (FVIIL) include genetic and environmental factors. We aimed to identify the cut-off FVIILs for general and severe bleedings in patients with FVIID by using an online national registry system including clinical, laboratory, and demographic characteristics of patients., Methods: Demographic, clinical, and laboratory data of patients with FVIID extracted from the national database, constituted by the Turkish Society of Hematology, were examined. Bleeding phenotypes, general characteristics, and laboratory features were assessed in terms of FVIILs. Bleeding rates and prophylaxis during special procedures/interventions were also recorded., Results: Data from 197 patients showed that 46.2% of patients had FVIIL< 10%. Most bleeds were of mucosal origin (67.7%), and severe bleeds tended to occur in younger patients (median age: 15 (IQR:6-29)). Cut-off FVIILs for all and severe bleeds were 16.5% and 7.5%, respectively. The major reason for long-term prophylaxis was observed as central nervous system bleeding (80%)., Conclusion: Our data are consistent with most of the published literature in terms of cut-off FVIIL for bleeding, as well as reasons for prophylaxis, showing both an increased severity of bleeding and younger age at diagnosis with decreasing FVIIL. However, in order to offer a classification similar to that in Hemophilia A or B, data of a larger cohort with information about environmental and genetic factors are required.

Objectives: Recombinant fusion protein linking activated factor VIIa to human albumin (rVIIa-FP) is a therapeutic option designed to prevent and treat bleeding events in patients with congenital FVII deficiency with reduced infusion frequency compared to current FVII treatments. This study characterized the pharmacokinetics (PK) and pharmacodynamics (PD) of rVIIa-FP. Methods: A phase I multicenter, randomized, open-label, parallel-arm, single-dose study (NCT02470871) was conducted in nine patients with severe congenital FVII deficiency. Patients received their routine FVII product (30 IU/kg plasma-derived FVII [pdFVII] or 25 μg/kg recombinant activated FVII (rFVIIa) [eptacog alfa]), and were then randomly assigned to receive 100 or 300 μg/kg of rVIIa-FP. Blood samples for PK and PD assessments were drawn up to 48 hr after administration. FVIIa activity was determined using a one-stage clotting assay. PD parameters were derived from thrombin generation testing, using the Nijmegen hemostasis assay. Results: rVIIa-FP showed improved PK compared to rFVIIa, with 2- to 3-fold longer t 1/2 and 4- to 8-fold lower clearance. Analysis of PD data showed a sustained suppression of lag time below 4.5 min (upper limit of healthy people) for rVIIa-FP compared to rFVIIa. AUEC and EC max were similar across the two dose groups of rVIIa-FP and rFVIIa. Discussion : rVIIa-FP was well tolerated in patients with congenital FVII deficiency, showed a longer half-life and lower clearance compared to rFVIIa, and lag time remaining within healthy ranges for ≥8 hr. Conclusion: These results warrant further investigation into the efficacy of rVIIa-FP to control and prevent bleeding in patients with FVII deficiency.

Introduction: Inherited factor VII deficiency is the most common autosomal recessive inherited bleeding disorder, with an estimated incidence of one per 500 000 cases in the general population. Bleeding manifestations correlate poorly with circulating FVII levels. During pregnancy, increases in FVII levels can occur in women with mild-moderate FVII deficiencies but not in those with severe deficiency., Aim: We present five pregnant patients with FVII deficiency and describe the management during their pregnancies and peripartum periods., Methods: Retrospective analysis of six pregnancies in five women with FVII deficiency followed during pregnancy and delivery at an academic medical centre between January 2013 and December 2019., Results: Of the five patients, two had severe, one with moderate and two with mild FVII deficiency. Early postpartum haemorrhage (PPH) occurred in two patients. One of the two severe FVII-deficient patients had PPH with a laceration at delivery despite replacement therapy with recombinant factor VII. The other PPH occurred in a patient with mild FVII deficiency who delivered twins by caesarean section under general anaesthesia. Neuraxial anaesthesia was utilized in only one woman with mild deficiency whose FVII level normalized at the end of the pregnancy., Conclusions: Management of delivery for women with FVII deficiency should be addressed on a case-by-case basis at centres with expertise in rare bleeding disorders, maternal foetal medicine and obstetric anaesthesiology. These management discussions should factor the patient's bleeding history, third trimester PT, FVII level, multiple gestation and mode of delivery., (© 2020 John Wiley & Sons Ltd.)

Factor VII (FVII) deficiency is the most common of the Rare Inherited Coagulation Disorders. The inheritance is autosomal recessive but there is variable penetrance. Overall there is poor correlation between the FVII level and the bleeding phenotype. Heterozygotes may have significant bleeding and severe homozygotes, or compound heterozygotes can be asymptomatic. Typically, homozygotes have FVII levels <10% and heterozygotes have levels above that. In most cases bleeding is uncommon with FVII levels>10-20%. A personal and family history is essential to determine the bleeding risk and to plan for surgical and obstetrical prophylaxis. Severe bleeding complications including central nervous system bleeding, gastrointestinal system bleeding and bleeding into the joints occurs in 10-15% of FVII deficient patients. Mucocutaneous bleeding is a common symptom but 30% of patients are asymptomatic. Fifty to 69% of women have heavy menstrual bleeding. Due to the limited number of publications regarding this rare disorder there are no consensus guidelines. There is registry data which has led to the best recommendations for treatment of bleeding episodes, initiation of long-term prophylaxis in addition to surgical plus ante and peripartum prophylaxis. Recombinant FVII concentrate is the best replacement therapy and a review of treatment and prophylaxis dosing is discussed., (Copyright © 2019. Published by Elsevier Ltd.)

Congenital factor VII deficiency is a rare autosomal recessive disorder associated to different haemorrhagic manifestations. Labour and delivery may cause bleeding risk in patients with this coagulation deficit, thus it is appropriate to clarify whether prophylaxis of peripartum haemorrhage is necessary. To date, there are very few cases in scientific literature which report the management of women with congenital factor VII deficiency during labour, and a consensus for prophylaxis does not exist. In this manuscript we present the management of a 35 years old woman with factor VII deficiency, treated with recombinant factor VIIa before delivery, without haemorrhagic complications either for the woman and for the infant. Therefore, we present a review of similar cases managed with a peripartum prophylaxis with recombinant factor VIIa, and discuss its usefulness and effectiveness, in view of the severity of the deficit and the doses used., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Organ transplant in patients with congenital bleeding disorders is a challenge requiring an integrated approach of various specialists. Inherited factor VII deficiency is the most common of the rare bleeding disorders, with a wide set of hemorrhagic features. Although a kidney allograft is the most frequent type of solid-organ transplant, it is rarely performed in individuals with congenital hemorrhagic disorders. Here, we highlight the course of a patient with coagulation factor VII deficiency who underwent successful kidney transplant without significant coagulopathy. Our patient was a 19-year-old man with end-stage kidney disease and congenital coagulation factor VII deficiency. Perioperative bleeding was successfully prevented by administration of recombinant factor VII, confirming its safety in solid-organ transplants. Success requires evaluation of doses and therapeutic schedules, as well as a multidisciplinary approach.

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.

: Congenital factor VII (FVII) deficiency is a rare bleeding disorder with an estimated prevalence of 1 per 500 000 in the general population. On-demand replacement therapy is the main therapeutic choice in patients with congenital FVII deficiency. Inhibitor formation against exogenous FVII is very rare and can cause challenges in the management of the disorder. The present study was conducted to assess the prevalence of FVII inhibitor in 50 patients with congenital FVII deficiency under on-demand or prophylaxis treatment by recombinant activated FVII. All patients with confirmed congenital FVII deficiency were assessed for inhibitor development in regular intervals. Inhibitor titer was determined by a modified Nijmegen-Bethesda assay. The study results were analyzed by SPSS software. Among all cases, two patients (4%) developed an FVII inhibitor. Case 1 was a 14-year-old boy with severe FVII deficiency (FVII activity <1%) with regular prophylaxis. The patient was a high-responder with high-titer FVII inhibitor (170 Bethesda Unit). This patient, who had a history of intracranial hemorrhage, had undergone brain surgery three times. The second patient was a 70-years old man with on-demand therapy that also developed a high-titer inhibitor (10 Bethesda Unit). This patient had experienced easy bruising and endured a few surgeries for his brain tumor and, finally, succumbed to the disease. Although the inhibitor formation is a rare phenomenon, it may result in a significant challenge to manage the affected patients.

Rationale: Congenital factor VII (FVII) deficiency is a rare coagulopathy. There are little clinical data for congenital FVII deficiency and no evidence-based medicine guidelines for treatment., Patient Concerns: A 48-year-old woman with gallbladder stones suffered from intermittent abdominal pain for 2 months that was accompanied by an abnormally prolonged prothrombin time., Diagnoses: The woman was diagnosed as having cholecystolithiasis with cholecystitis and congenital FVII deficiency., Intervention: Preoperative evaluation confirmed the necessity of recombinant activated factor VII (rFVIIa) replacement therapy. We monitored the plasma factor VII activity (FVII:C) and coagulation function, determined the half-life of rFVIIa in the patient, and administered personalized rFVIIa replacement therapy., Outcomes: Laparoscopic cholecystectomy was performed successfully, and the patient recovered well without any complications., Lessons: The clinical manifestations and severity of bleeding in patients with congenital FVII deficiency can vary widely. The history of massive bleeding and plasma FVII:C are the decisive factors when implementing a replacement therapy. The actual half-life of rFVIIa can be determined from intensive monitoring results of plasma FVII:C at the beginning of replacement therapy, which could further guide the personalization of rFVIIa replacement therapy.

İnce Z, Bulut Ö, Tuğrul-Aksakal M, Ünüvar A, Devecioğlu Ö, Çoban A. Asymptomatic intracranial hemorrhage in a newborn with congenital factor VII deficiency and successful treatment with recombinant activated factor VII. Turk J Pediatr 2018; 60: 562-565. Intracranial hemorrhage is considered the most common cause of death in newborns with congenital factor VII (FVII) deficiency. Recombinant activated FVII (rFVIIa) provides specific replacement therapy, however there is limited experience with its neonatal use. We describe our experience about the treatment of intracranial hemorrhage in a newborn with congenital FVII deficiency and emphasize the importance of imaging in asymptomatic patients. She presented with ecchymoses on her skin, no other pathological clinical signs, prolonged PT, normal PTT and FVII activity of 2%. Intracranial hemorrhage was diagnosed while screening for internal bleedings. Treatment with rFVIIa resulted in stabilization and regression of the hematoma.

Factor VII (FVII) deficiency is one of the rare inherited bleeding disorders. Thrombosis has been occasionally described in inherited FVII deficiency. Here, we report a young female with undiagnosed FVII deficiency who presented with cerebral venous sinus thrombosis (CVST). Oral contraceptive pill was found to be prothrombotic risk factor. The CVSToccurred in spite of the congenital FVII deficiency indicating that no definitive antithrombotic protection is assured by this defect. Low molecular weight heparin and anti-Xa assay were found to be safe choice of anticoagulation and monitoring, respectively, in this patient.

Development of neutralising antibodies (inhibitors) against factor VIII (FVIII) is a frequent and severe complication of replacement therapy in haemophilia A. Previous data from haemophilia A mouse model demonstrates that both CD32 inhibition and high doses of rhFVIII prevent the differentiation of FVIII-specific memory B cells (MBCs) into antibody secreting cells (ASCs). Here, cellular targets responsible for the suppression of ASC formation by means of CD32 inhibition and high dose of rhFVIII were analysed. We investigated apoptosis on FVIII-specific MBCs using a pan caspases inhibitor, and screened for defects in rhFVIII presentation by analysing T cell release of Th1- and Th2-cytokines in vitro. Although high dose of rhFVIII suppressed ASC formation, cytokine response was not affected. Upon re-stimulation of splenocytes with high dose of rhFVIII, prevention of apoptosis fully restored the FVIII-specific recall response. In contrast, genetic deletion or inhibition of CD32 significantly altered Th1- and Th2-response. CD32 blockade and inhibition of apoptosis resulted in a partial rescue of FVIII-specific ASCs. Normal cytokine secretion could not be restored. In conclusion, suppression of FVIII-specific recall response by CD32 and high doses of rhFVIII is mediated by distinct mechanisms. High dose of rhFVIII induces apoptosis in FVIII-specific MBCs but does not influence FVIII-specific T cell response. CD32 blockade, however, may suppress the FVIII-specific recall response by two ways: i) increasing apoptosis of FVIII-specific MBCs and ii) disturbing FVIII-specific T cell response by modulating presentation of rhFVIII to CD4 + T cells in vitro.

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: A paucity of data exists on the incidence, diagnosis and treatment of bleeding in women with inherited factor VII (FVII) deficiency., Aim: Here we report results of a comprehensive analysis from two international registries of patients with inherited FVII deficiency, depicting the clinical picture of this disorder in women and describing any gender-related differences., Methods: A comprehensive analysis of two fully compatible, international registries of patients with inherited FVII deficiency (International Registry of Factor VII deficiency, IRF7; Seven Treatment Evaluation Registry, STER) was performed., Results: In our cohort (N = 449; 215 male, 234 female), the higher prevalence of mucocutaneous bleeds in females strongly predicted ensuing gynaecological bleeding (hazard ratio = 12.8, 95% CI 1.68-97.6, P = 0.014). Menorrhagia was the most prevalent type of bleeding (46.4% of patients), and was the presentation symptom in 12% of cases. Replacement therapies administered were also analysed. For surgical procedures (n = 50), a receiver operator characteristic analysis showed that the minimal first dose of rFVIIa to avoid postsurgical bleeding during the first 24 hours was 22 μg kg(-1) , and no less than two administrations. Prophylaxis was reported in 25 women with excellent or effective outcomes when performed with a total weekly rFVIIa dose of 90 μg kg(-1) (divided as three doses)., Conclusion: Women with FVII deficiency have a bleeding disorder mainly characterized by mucocutaneous bleeds, which predicts an increased risk of ensuing gynaecological bleeding. Systematic replacement therapy or long-term prophylaxis with rFVIIa may reduce the impact of menorrhagia on the reproductive system, iron loss and may avoid unnecessary hysterectomies., (© 2016 John Wiley & Sons Ltd.)

Rare coagulation disorders (RCDs) include the inherited deficiencies of fibrinogen, factor (F) II, FV, combined FV and VIII, FVII, FX, combined FVII and X, FXI, FXIII and combined congenital deficiency of vitamin K-dependent factors (VKCFDs). Despite their rarity, a deep comprehension of all these disorders is essential to really understand haemostasis. Indeed, even if they share some common features each RCD has some particularity which makes it unique. In this review, we focus on three disorders: fibrinogen, FVII and FXIII., (© 2016 John Wiley & Sons Ltd.)

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

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.)

Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

An 81-year-old man was referred to our department because of suspected factor VII (FVII) deficiency. His FVII activity was under 1%, whereas the FVII activity levels of his son and granddaughter were 65 and 109%, respectively. The nucleotide at position 3886 of his FVII gene was homozygous for G. A single T to G substitution results in the replacement of wild-type Cys at residue 22 by Gly. His son was heterozygous for G and T at position 3886, whereas his granddaughter was homozygous for wild-type T. These results suggest that he was homozygous for FVII Cys22Gly. He underwent radiofrequency ablation (RFA) for hepatocellular carcinoma, receiving 20 μg/kg of recombinant FVIIa prior to RFA and 10 μg/kg of recombinant FVIIa twice after RFA. He showed no bleeding tendency; however, a myocardial infarction was diagnosed and percutaneous coronary intervention was performed.

In order to establish the efficacy and biosimilar nature of AryoSeven to NovoSeven in the treatment of congenital factor VII (FVII) deficiency, patients received either agent at 30 μg/kg, intravenously per week for 4 weeks, in a randomized fashion. The primary aim was to compare FVII:coagulation activity (FVII:C), 20 minutes after recombinant activated FVII (rFVIIa) injection, in the 2 groups. A secondary measure was self-reported bleeding. The median interquartile baseline range of the plasma level of activated FVII (FVIIa) activity in the 2 groups was 1.6 (1.1-14.0) IU/dL and 5.0 (1.1-25.5) IU/dL. All patients achieved levels of FVIIa (FVII:C) >30 IU/dL, 20 minutes after the injection of rFVIIa. Bleeding was similar between the 2 groups, with a comparable decrease in severity and frequency compared to the last month prior to treatment. AryoSeven is similar to NovoSeven in increasing postinjection FVIIa activity as well as in clinical safety and efficacy., (© The Author(s) 2014.)

This study presents the demographics, clinical spectrum, and outcome of patients with congenital factor VII (FVII) deficiency at a tertiary care center over a period of 12 years. Of the 49 patients, 27 (55%) patients were males. Consanguinity was found in 92% of the patients. The median age of symptom onset was 2.4 (interquartile range [IQR]: 1.1-6.5) years with a median age of 5.8 (IQR: 3.1-10) years at diagnosis. Life-threatening complications like intracranial bleeding (ICB) and intra-abdominal bleeding (IAB) were observed in 8 (16.4%) patients. We found that 11 (55%) of the 20 patients with FVII coagulant activity (FVIIc) <1% were either asymptomatic or showed mild phenotype. In contrast, 9 (53%) of the 17 patients with FVIIc >5% were affected by severe symptoms. Age <1 year was the only identified risk factor associated with development of life-threatening bleeding episodes (P = .042; odds ratio 6.46). Overall, 4 (8.2%) died as a consequence of ICB (3 patients) and IAB (1 patient)., (© The Author(s) 2013.)

Factor VII (FVII) deficiency is one of the two congenital coagulation disorders that was not discovered by the description of a new bleeding patient whose clotting pattern did not fit the blood coagulation knowledge of the time (the other is factor XIII deficiency). The existence of an additional factor capable of accelerating the conversion of prothrombin into thrombin was suspected before 1951, the year in which the first family with FVII deficiency was discovered. As several investigators were involved in the discovery of FVII deficiency from both sides of the Atlantic, several different names were tentatively suggested to define this entity, namely stable factor (in contrast with labile factor or FV), cothromboplastin, proconvertin, serum prothrombin conversion accelerator, prothrombin acceleration, and autoprothrombin I. The last term was proposed by those who denied the existence of this new entity, which was instead considered to be a derivate of prothrombin activation, namely autoprothrombin. The description of several families, from all over the world, of the same defect, however clearly demonstrated the singularity of the condition. Factor VII was then proposed to define this protein. In subsequent years, several variants were described with peculiar reactivity toward tissue thromboplastins of different origin. Molecular biology techniques demonstrated several gene mutations, usually missense mutations, often involving exon 8 of the FVII gene. Later studies dealt with the relation of FVII with tissue factor and activated FVII (FVIIa). The evaluation of circulating FVIIa was made possible by the use of a truncated form of tissue factor, which is only sensitive to FVIIa present in the circulation. The development of FVII concentrates, both plasma derived and recombinant, has facilitated therapeutic management of FVII-deficient patients. The use of FVIIa concentrates was noted to be associated with the occasional occurrence of thrombotic events, mainly venous. Total or partial liver transplants have been performed with success in these patients and have "cured" their deficiencies. Prenatal diagnosis has also been performed and recent research involves the development of inhibitors of FVII + tissue factor complex or of FVIIa. This approach, if successful, could provide another antithrombotic therapeutics tool. The story of FVII well summarizes the efforts of both theoretical and clinical approaches in the characterization of a coagulation disorder, that is, among the rare bleeding conditions, most frequently encountered in clinical practice., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Inherited factor VII (FVII) deficiency is a rare autosomal recessive hemorrhagic disorder. The major clinical symptoms include: bleeding from the oral cavity, epistaxis, menorrhagia, spontaneous hemarthros, bleeding to the gastrointestinal tract and central nervous system, and perioperative bleeding. The aim of this study was to present our experience in preventing bleeding and hemorrhagic disorders in surgical patients with inherited FVII deficiency by using recombinant activated FVIIa (rFVIIa), and with prothrombin complex concentrates (PCCs). In 2002-2011, 17 patients with inherited FVII deficiency underwent surgery. Thirteen patients had isolated FVII deficiency below 10%, and four patients 10-25. To prevent bleeding and hemorrhagic complications, we administered small single doses of rFVIIa (Novo-Seven) at 12-h intervals to 15 patients on surgery day and on day 1 following surgery, then every 24 h; PCCs were administered (Prothromplex, Beriplex) to two patients. No symptoms of bleeding, hemorrhagic or thromboembolic complications were observed in the perioperative and 1-month observation period in surgical patients treated with rFVIIa. One patient treated with PCC (Prothromplex) developed distal deep vein thrombosis on postoperative day 7. The results suggest that small, single, every 12-h doses of rFVIIa (NovoSeven) and in next days after surgery one time every 24 h are well tolerated and effective for prevention of thromboembolic, bleeding and hemorrhagic complications in FVII-deficient patients. Antithrombotic prophylaxis with low-molecular-weight heparin should be applied in patients using PCCs.

Recombinant activated factor VII (rFVIIa) was initially developed to treat bleeding episodes in patients with congenital hemophilia and inhibitors. Due to the initial success in this clinical setting, its use has been extended to other coagulopathies characterized by impaired thrombin generation, i.e. acquired hemophilia, inherited factor VII deficiency and Glanzmann's thrombasthenia, for which it is currently licensed. Extensive research in the last decade has increased our knowledge of the mechanisms utilized by rFVIIa to restore normal hemostasis. This paper reviews current understanding of the mechanisms of action of rFVIIa before summarizing the clinical experience, in terms of safety and efficacy, to date in its licensed indications.