Severe Congenital Factor VII Deficiency Research Articles

Interleukin 10, but not tumor necrosis factor-alpha, gene variations are associated with factor VII inhibitor development.

Development of alloantibodies against coagulation factor VII (FVII) is the main therapeutic challenge in severe congenital FVII deficiency. About 7% of patients with severe congenital FVII deficiency develop an inhibitor against FVII. In this research, the relationship between interleukin (IL)-10 and tumor necrosis factor-alpha (TNF)-α gene variants and inhibitor development was evaluated for a group of Iranian patients with severe congenital factor VII deficiency. Patients with FVII deficiency were divided into 2 groups: 6 cases and 15 controls. Genotyping was performed using the amplification-refractory mutation system polymerase chain reaction. We found that IL-10 rs1800896 A>G gene variant is associated with the risk of FVII inhibitor development (OR = 0.077, 95% CI = 0.016-0.380, P = .001), whereas the TNFα-rs1800629G>A variant has no relation with inhibitor development in severe FVII deficiency. The results show that the IL-10 rs1800896 A>G variant increases the risk of developing an inhibitor in patients with severe congenital FVII deficiency.

Primary prophylaxis for children with severe congenital factor VII deficiency — Clinical and laboratory assessment

Severe congenital factor VII (FVII) deficiency is a rare bleeding disorder. Prophylaxis with replacement therapy has been suggested to patients, yet the most beneficial dosing regimens and therapy intervals are still to be defined. Due to the lack of evidence-based data, we hereby present our experience with long-term administration and monitoring primary prophylaxis in children with severe FVII deficiency and an extremely high bleeding risk.Four children with familial FVII deficiency, treated by prophylactic recombinant activated factor VII (rFVIIa), 15–30μg/kg/dose, given 2–3 times weekly since infancy, are discussed. Clinical follow up and monitoring laboratory assays, including thrombin generation, measured at various time points after prophylactic rFVIIa administration are presented.Among our treated patients neither FVII activity nor thrombin generation parameters (both already declined 24h post rFVIIa administration) were able to predict the impact of prophylaxis, and could not be used as surrogate markers in order to assess the most beneficial treatment frequency. However, the long clinical follow-up and comprehensive laboratory assessment performed, have shown that early primary prophylaxis as administered in our cohort was safe and effective.

A novel homozygous missense mutation in the factor VII gene of severe factor VII deficiency in a newborn baby

A term male infant born to nonconsanguineous parents was admitted to the hospital for evaluation of lethargy and a pale appearance on the third day of life. He had anemia from an intracranial hemorrhage, and his coagulation factor assay revealed that his bleeding episode was due to severe congenital factor VII deficiency (5% of normal activity). An A-to-G point mutation in the acceptor splice site of intron 5 was identified at nucleotide position 9418. Sequence analysis of the factor VII gene in the parents revealed that they were both heterozygous for a G-to-A transversion at nucleotide position 9418 (IVS5-1) between intron 5 and exon 6. A genetic study involving a patient with a congenitally inherited disease and the parents can confirm the genetic background of the disease and can be used for prenatal guidance to exclude severe bleeding disorders.

Successful coronary artery bypass graft surgery in severe congenital factor VII deficiency: Perioperative treatment with factor VII concentrate

Successful coronary artery bypass graft surgery in severe congenital factor VII deficiency: Perioperative treatment with factor VII concentrate -

Total Hip Arthroplasty in Severe Congenital Factor VII Deficiency: Successful Use of Recombinant Activated Factor VII for Hemostasis

Congenital factor VII (FVII) deficiency is a rare hemorrhagic disorder, and, in affected patients, surgery is likely to cause excessive bleeding. In this article, we report the first case of total hip arthroplasty in a patient with severe congenital FVII deficiency in which recombinant activated factor VII (rFVIIa, NovoSeven) was successfully used to manage bleeds. The patient was a 68-year-old woman with severe congenital FVII deficiency, who suffered from a hemorrhagic arthrosis of her left hip joint. We administered rFVIIa as intermittent bolus infusions both perioperatively and postoperatively; dosing was based on the results of a preoperative rFVIIa challenge test. During surgery and the 3-day postoperative treatment period, we observed normal hemostasis with no excessive bleeding or complications.

USE OF RECOMBINANT FACTOR VIIA IN PAEDIATRIC PATIENTS WITH LIVER FAILURE AND SEVERE COAGULOPATHY

P701 Aims: The only approved indications for recombinant Factor VIIa (rFVIIa, NiaStase, Novo Nordisk) in Canada are patients with inhibitors in haemophilia A or B and severe congenital factor VII deficiency. There have been a number of small trials studying its uses in non haematological indications, including liver disease and transplantation. A recent study reported improvement in PT’s in children with liver failure (Brown et al J.Ped. Gastroenterol. Nutr. 37:268, 2003).; however, there are few reports of its use in children with liver failure. Recently, we have used rFVIIa in 3 patients with liver failure, severe coagulopathy with bleeding who demonstrated signifcant laboratory and clinical improvement and no side effects. Patients and Methods: Patient 1 was an 11-y old boy with TPN-induced liver failure from short bowel who had 2 to 3 bleeds daily from his duodenostomy in addition to frequent nose bleeds. He was receiving: fresh frozen plasma (ffp) 20-30 ml/kg/d, a continuous octreotide infusion (20 to 80 μg/hour) aprotonin, thrombostatin and platelets to try and control his bleeding with minimal success. He received 0.2mg/kg/dose of rFVIIa on 5 separate occasions for acute bleeds which had not resolved within 3 hours after his usual treatment. His INR (normal 0.9 to 1.1) improved from 1.9 +/- 0.15 to 1.3 +/-0.15 and his factor VII level (normal 0.42 to 1.58 U/ml) increased from 0.44 U/ml to 1.4 U/ml. More importantly each of his bleeding episodes stopped within 10 minutes of administering the rFVIIa. Patient 2 was a 7 mo old girl with biliary atresia who developed acute on chronic liver failure with an INR ranging from 3.4 to 5.8 and bleeding from multiple sites despite 20 to 30 ml/kg/d of ffp. At the time of transplant she received 0.3 mg/kg of rFVIIa at the start of her liver transplant. One hour post infusion, her INR decreased from 3.4 to1.2, her factor VII level increased from 0.06 to 15.1 and her bleeding stopped. Patient 3 was a 3 mo old boy with fulminant liver failure of unknown etiology, bleeding from multiple sites and an INR ranging from 3.2 to 5.3. He was given 0.13 mg/kg of rFVIIa 1 hour prior to a liver biopsy and a second dose 2 hours later. His INR improved from 3.2 to 1.0, his factor VII level increased from 0.05 to 1.57 and there was no bleeding or other complications from the biopsy or the rFVIIa. Twenty hours later his INR was 2.3 and his factor VII level was 0.1 U/ml. Conclusions: Consistent with other reports, rFVIIa provided significant benefit in these children with liver failure and severe coagulopathy, in terms of clinical and laboratory improvement in their bleeding and coagulation profiles. There were no obvious side effects from the rFVIIa. This drug may be an important tool in the treatment of children with liver failure and more study is needed to define the optimal dosing for children.

Cardiac Surgery with Extracorporeal Circulation in Severe Factor VII Deficiency

We describe here successful open heart surgery with extracorporeal circulation and haemodilution in a child with severe congenital factor VII deficiency. Substitution therapy was realized with factor VII concentrate (SD proconvertin concentrate, Bio-Transfusion). This is the first report case of successful cardiac surgery in severe congenital factor VII deficiency.

Surgery for Scoliosis in Congenital Factor VII Deficiency

A patient with severe congenital factor VII deficiency had an anterior and posterior spine fusion for severe scoliosis. For both operations, hemostatic management was 50 units of prothrombin complex concentrate (Konyne) per kilogram of body weight before surgery and every eight hours after surgery for the first 24 hours. Subsequently, 10 mL/kg of fresh frozen plasma was given daily for five days. No bleeding problems were encountered. A treatment protocol is outlined for replacement therapy management during surgery for patients with severe factor VII deficiency. Managing hemostatic control during surgery in patients with severe factor VII deficiency is relatively easy.