Isolated Factor VII Deficiency Research Articles

Acquired isolated factor VII deficiency in a patient with myxoid pleomorphic liposarcoma, case report

Introduction: Acquired factor VII (FVII) deficiency is a rare condition with various causes, including acquired inhibitors to FVII, liver disease, and malignancies. Myxoid pleomorphic liposarcoma is a rare and aggressive form of soft tissue sarcoma that can cause a range of clinical manifestations, including bleeding and clotting disorders. Patient concerns and diagnosis: We present a case report of a 21-year-old man with severe acquired FVII deficiency due to mediastinal myxoid pleomorphic liposarcoma. The patient presented with elevated International normalized ratio (INR) and a severe reduction in FVII coagulant activity, unresponsive to conventional therapy. While an acquired inhibitor to FVII was initially suspected, negative results from laboratory testing, including protein G sepharose adsorption and a Bethesda assay using Immunoglobulin G purified from patient plasma, made the diagnosis of an acquired inhibitor to FVII uncertain. Interventions and outcome: The patient underwent surgical resection of the tumor, supported by recombinant FVII infusion, leading to the normalization of coagulation parameters. However, a relapse of the disease was detected 6 months later when he was noted to have a decline in FVII levels. Conclusion: This case highlights the importance of considering rare causes of bleeding and clotting disorders, particularly in unresponsive or atypical presentations. It also underscores the need for close monitoring and follow-up in patients with acquired FVII deficiency, even after successful treatment.

Factor VII Deficiency in Systemic Primary Amyloidosis: A Rare Case

Introduction: Isolated and combined factor deficiencies are known to occur in systemic primary amyloidosis. The most common factor deficiency known in these cases is isolated factor X deficiency. Other factor deficiencies are relatively less frequent. Isolated factor VII deficiency occurs very rarely in cases of systemic primary amyloidosis.Case report: A 58-year-old male patient previously presenting to another health center with complaints of generalized edema, fatigue, and itching had proteinuria and then he was diagnosed with systemic primary amyloidosis after the renal biopsy for proteinuria etiology. The patient’s laboratory tests showed prolongation of prothrombin time and factor VII deficiency. The patient responded well to the treatment for primary amyloidosis and factor VII deficiency.Discussion: In cases of systemic primary amyloidosis, if the etiology of prolonged prothrombin time involves no liver disease, warfarin use, or malabsorption, physicians should always keep in mind rare factor deficiencies such as factor VII deficiency, along with common factor deficiencies.

Complicated Portal Cavernoma Cholangiopathy (PCC) in a Patient with Pre-existing TIPS Managed Successfully by Endoscopic Biliary Stenting

PCC is the presence of typical cholangiographic changes in patients with a portal cavernoma due to chronic portal vein thrombosis (PVT), in the absence of other biliary tract diseases. Symptomatic PCC is rare; estimates range between 5-38% of patients with PVT. A 41 year old black woman with a PMH of Hodgkin's lymphoma s/p chemotherapy, isolated factor VII deficiency, complicated cirrhosis s/p TIPS and PVT presented to GI clinic with RUQ pain, dark urine, and acholic stool. Physical examination revealed scleral icterus and RUQ tenderness. The total bilirubin was 3.3 MG/DL, AST 111 U/L, ALT 29 U/L, ALP 603, and INR 1.4. After hospitalization, MRCP and MRI pancreas revealed cavernous portal vein transformation and chronic intrahepatic biliary dilation compatible with PCC. There was narrowing of the biliary system at the confluence secondary to extrinsic compression from cavernous transformation. No CBD dilation or filling defects, pancreatic mass, or PD dilation was noted. ERCP with an occlusion cholangiogram revealed a normal CBD. Unexpected vigorous hemobilia was encountered. Cholangioscopy was limited by fresh blood and clots up to the confluence - a bleeding source could not be identified. Interventional Radiology was consulted. CT angiogram revealed no active bleeding. TIPS was patent. Overnight the patient developed fever, leukocytosis, increasing RUQ abdominal pain, and worsening bilirubin consistent with ascending cholangitis. Antibiotics were initiated. Emergent ERCP was performed. Balloon sweeps of the CBD extracted clots and re-precipitated hemobilia. Cholangiogram revealed turbulence and dilution of contrast at the confluence, suggesting a bleeding source in the vicinity. A fully covered metallic stent was deployed at the confluence. Cholangioscopy was performed through the stent. No active bleeding was noted. The patient did well post procedure with resolution of bleeding, pain, and fever. Treatment of complicated PCC is multi faceted. It involves endoscopic biliary decompression followed by portal decompression (proximal splenorenal shunt or TIPS). Patients who remain symptomatic may undergo biliary drainage surgeries (hepaticojejunostomy or choledochojejunostomy). Hemobilia has been reported rarely after balloon sweeps, attributed to suspected intracholedochal varices and managed successfully by covered metal stents.Figure 1Figure 2Figure 3

FACTOR VII DEFICIENCY IN POLISH HOUND – ACCIDENTAL EVENT OR NEW PERMANENT RISK?

The Polish Hound (ogar polski) is a small, old breed of hunting dogs.The breed was recognized by the Fédération Cynologique Internationale (FCI) in 1966.A three–year–old Polish Hound male, was admitted to the Clinic of Internal Diseases of Companion Animals of Life Science University in Lublin because of signs of haemorhagic diathesis. There was no preceding history of trauma. General clinical examination was unremarkable. On initial diagnostic testing prothrombin time (PT)of the patient was prolonged nearly by three times. To characterize the dog’s coagulopathy further, samples were collected for coagulation screening tests, mixing studies and factor analyses. Investigations revealed factor VII activity below 2%.Unfortunately we had been unable to determine whether the disorder is inherited or is the result of a spontaneous mutation. It is very likely that the nature of described deficit is inherited. Canine hereditary FVII deficiency was first described in 1962 as an incidental finding in Beagles. Later, the defect was identified in another breeds, such as: English Bulldogs, Alaskan Malamutes, Miniature Schnauzers, Boxers, Scottish Deerhounds, Alaskan Klee Kai Dog and mixed–breed dogs. In 2005 a molecular characterization of FVII deficiency in Beagles was described. Unfortunately we had been unable to determine whether the disorder is inherited or is the result of a spontaneous mutation. To our knowledge this case is the first to report of isolated factor VII deficiency in Polish Hound.

Acquired Isolated FVII Deficiency: An Underestimated and Potentially Important Laboratory Finding.

To investigate all cases of isolated factor VII (FVII) deficiency as gathered from personal files or by a PubMed search. Personal files dealing with patients studied in Padua during the years 1970 to 2010 were reevaluated. The PubMed search was time unlimited and was carried on 2 occasions during 2014. Cross-checking of the references, listed in every article, was also carried out to avoid omissions. Inclusion criteria were isolated FVII defect of less than 40% of normal, negative coagulation pattern in the family, normal level of other vitamin K-dependent clotting factors, and normalization of the clotting factor after the therapeutic procedures, unless the patient died. Twenty-nine patients met the inclusion criteria (18 male and 9 female, in 2 cases gender was unreported). This number included 1 personal case. Mean age was 37.9 (range 3-80). Underlying diseases were the following: neoplasia, infections, polytrauma, penicillin administration, nephrotic syndrome Wiskott Aldrich syndrome, and left heart failure (1 case, each); 2 patients had no underlying disease. Bleeding was variable but usually mild. There were 11 fatalities. Isolated FVII deficiency is a rare defect, which appears to be a finding associated with several morbid conditions, especially sepsis and tumors. This indicates the need for a careful investigation of even a mild prolongation of prothrombin time, especially when fibrinogen and partial thromboplastin time are normal.

Prevention of bleeding and hemorrhagic complications in surgical patients with inherited factor VII deficiency.

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.

Factor VII Deficiency In African American Individuals. Presentation, Diagnosis and Management.A Single Medical Center Experience

Background Factor VII (FVII), a vitamin K-dependent glycoprotein serine protease, is produced by the liver and plays a fundamental role in the activation of the extrinsic coagulation pathway. Hereditary factor VII deficiency is a rare coagulation disorder with autosomal recessive inheritance and an approximate prevalence of 1:500,000. Clinical manifestations vary from no symptoms to severe bleeding events and often correlate poorly with plasma levels of factor VII. Therapy for factor VII deficiency depends on the severity and the type of bleeding and includes fresh frozen plasma (FFP), antifibrinolytics and recombinant factor VIIa (rFVIIa). Recent data from the STER registry suggests that bleeding symptoms on presentation and factor VII activity level can be used to identify clinical variants and guide replacement therapy. The majority of patients enrolled in this registry were from European countries. Patients of African American origin remain poorly characterized. Aims We present our experience with diagnosis and management of patients, predominantly African American, in a large academic institution. We retrospectively reviewed the data on seven patients diagnosed with isolated factor VII deficiency and their management. Results Six of the seven patients followed in our institution were African American. Of them, three were female and three were male. A six month old girl was diagnosed during treatment for sepsis. She had no bleeding symptoms (FVII activity 27% on presentation, 32% one month later). The other two female patients presented with obstetrical bleeding (FVII <3% and 11% respectively). Of the male patients, two six year old twins had epistaxis (FVII activity 12%). Another six year old boy presented with trauma-associated hemorrhage, but had no prior history of bleeding (FVII 4%). Follow up data were available on five of the patients. Duration of follow up ranged from 6 months to more than 10 years. None of the patients had spontaneous bleeding, regardless of their presentation or level of FVII activity. The patients with bleeding and those who needed surgery received FFP (two patients prior to making the diagnosis) and rFVIIa (four patients). The doses used were 10-25mcg/kg in one or two applications. No bleeding and no thrombotic complications were observed with this therapy. None of the patients received antifibrinolytics. The one White Caucasian patient was a 25 year old male who presented with bleeding after trauma (FVII activity was 10%) and was managed with rFVIIa (25mcg/kg). Conclusion Our data demonstrates that, in African American patients, factor VII deficiency presents with variable clinical findings. There was poor correlation between the FVII levels and the clinical phenotype. Management with rFVIIa, used at the time of surgery or trauma at low to intermediate doses, was sufficient to prevent bleeding and was not associated with any significant complications. Disclosures: No relevant conflicts of interest to declare.

Aortic valve replacement in a patient with factor VII deficiency

A 69-year-old man who had never experienced episodes of bleeding was admitted to our hospital with the complaints of dyspnea, palpitation and orthopnea. Electrocardiography, echocardiography and laboratory tests revealed atrial fibrillation, severe aortic stenosis and elevated INR level (2.18). Coagulation tests due to isolated INR elevation showed that the activity of factor VII (FVII) decreased to 9% and the patient was diagnosed with isolated FVII deficiency. As FVII activity<10% is associated with high risk of bleeding during surgical procedures, recombinant FVII (rFVIIa) 40 mcg/kg was administered intravenous bolus infusion two hours before surgery. Aortic valve replacement was performed using a-23 mm bioprosthesis. The activity level of FVII during anesthesia induction and aortic cross declamping were 29% and 22%, respectively. Hemostasis was easy to secure and no extra dose of rFVIIa was given. The patient did not experience any postoperative problem or severe bleeding. Warfarin sodium was not administered to the patient, as he had atrial fibrillation, as well as bioprosthesis implantation and an INR level of 2.5. At the end of a-two-year follow-up period, the patient had a good exercise tolerance without any bleeding or thromboembolic complication. Factor VII deficiency is an extremely rare inherited bleeding disorder. Replacement therapy with rFVIIa with close monitoring of FVII activity is a reliable way to manage patients with FVII deficiency who are scheduled to undergo valvular cardiac surgery.

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient’s past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

A Spectrum of Clinical and Laboratory Findings and Treatment Modalities in Patients with Factor VII Deficiency- A Single Medical Center Experience,

Abstract 3306▪▪This icon denotes a clinically relevant abstract Introduction:Factor VII, a vitamin K dependent glycoprotein serine protease secreted by the liver, has a fundamental role in the activation of the extrinsic coagulation pathway. It is found in the plasma as a zymogen, and is activated by tissue factor and calcium. Hereditary factor VII deficiency is a rare coagulation disorder with autosomal recessive inheritance found approximately at a prevalence of 1:500,000. In Israel, factor VII deficiency is found mostly in Sephardic Jews of Iranian, Moroccan and Tunisian origin as well as in the Druze population. Bleeding symptoms usually occur in homozygotes or compound heterozygotes. In symptomatic patients, the clinical severity of bleeding ranges from mild to severe (such as intracranial bleeding) and does not always correlate with plasma levels of factor VII activity. However, patients with factor VII activity of less than 1% may present with symptoms similar to severe hemophilia. Patients with factor VII activity of 5% or more usually present with milder bleeding such as epistaxis, gingival bleeding, menorrhagia or bruising. Therapy for factor VII deficiency depends on severity and type of the bleeding. Treatment includes fresh frozen plasma (FFP), tranexamic acid and recombinant factor VIIa (Novoseven). Aims:The study goal was to find correlation between level of factor VII activity, bleeding complications and treatment modalities that were used in symptomatic patients or in those undergoing surgical procedures. Patients and methods:We performed a retrospective study of 125 patients with decreased levels of factor VII, referred to our department between 1990–2010. 56 patients with isolated deficiency of factor VII were included in the study. Patients with combined deficiencies or liver disease were excluded. Demographics, clinical symptoms and their correlation to levels of factor VII, as well as treatment modalities were investigated. A factor VII activity level below 50 % was considered as decreased. The data collection was performed after approval of hospital Helsinki committee. Results:Of 56 patients with isolated factor VII deficiency there were 29 males and 27 females. 31/56 (55.4%) of the patients were Jews of Sephardic origin. 18/56 (32%) of the patients had relatives with known factor VII deficiency. The activity of factor VII ranged from <1%-49%. There was no significant difference in factor VII activity levels between the symptomatic (mean = 20.87, SD = 17.9) and the asymptomatic patients (mean = 23.13, SD = 17.4). 11/56 (19.6%) of the patients had clinical symptoms of bleeding, 6 of them had factor VII level<10 %. No life threatening bleeding was reported. Most episodes of bleeding related to factor VII deficiency were epistaxis and menorrhagia. Less common bleeding included hematoma and gingival bleeding. Only 9% of the symptomatic patients required treatment with FFP or tranexamic acid. Recommendation for prophylactic treatment such as FFP and/or tranexamic acid prior to surgical procedure was given in 19 patients. The post operative period was uneventful in all the patients. 5 patients did not receive any prophylactic treatment for different surgical procedures and no significant post operative bleeding was observed. Conclusions:Though factor VII deficiency had been described in the literature as a rare disease, we collected and analyzed a large cohort of 56 patients with this disorder in a single medical center. Most of our patients were Sephardic Jews. There had been several reports of excessive bleeding which complicated surgery, especially of the oropharynx and urogenital tract in patients with factor VII deficiency. Levels of 15–25% are recommended for surgery, but the plasma factor VII level required for surgery has been not formally established. We did not find statistically significant differences in factor VII activity levels between the symptomatic patients and the asymptomatic ones (P value<0.36). No life threatening bleeding occurred; only one patient required acute treatment to stop the bleeding. There was no uniform protocol used for prophylactic treatment, which was usually based on “old” drugs such as FFP and tranexamic acid. There was no need for Novoseven. We conclude that treatment guidelines based on the family, personal, surgical history and laboratory results are required for optimal treatment of patients with inherited factor VII deficiency. Disclosures:No relevant conflicts of interest to declare.

Déficit acquis et isolé en facteur VII contemporain d'un traumatisme crânien grave : utilisation du substitut de facteur VII (facteur VII-LFB ®)

We report a case of transient acquired and isolated factor VII deficiency associated with severe head trauma. A 16-year-old boy was involved in a motor vehicle accident. CT scan showed frontal brain contusion and a cerebral haematoma (5 cm). First prothrombine time (PT) was normal. Rapidly, a severe coagulopathy developed, unresponsiving to fresh frozen plasma and vitamin K. Haemostatic markers analysis showed an isolated deficiency of factor VII at 15%. No inhibitory activity against factor VII could be detected. We successfully treated the deficiency with intermittent intravenous human factor VII (factor VII-LFB ®) during 10 days. Factor VII return to normal at 84%. Physiopathological and therapeutic aspects of this rare pathology are presented.

Acquired isolated factor VII deficiency during sepsis.

Isolated acquired factor VII deficiency is uncommon. We report 11 cases of acquired factor VII deficiency associated with severe systemic sepsis. All patients initially displayed a heterozygous-like factor VII deficiency confirmed by both clotting and amidolytic assays, associated with low factor VII antigen levels, and increased haemostasis markers (D-dimers, prothrombin fragments 1.2, thrombin-antithrombin complexes). After sepsis recovery, normal factor VII levels were evidenced. Isolated factor VII consumption or proteolytic degradation by leucocyte proteases can be evoked, but the mechanism of acquired factor VII deficiency during sepsis remains to be elucidated. The knowledge of this syndrome should avoid false diagnosis of congenital factor VII deficiency.