1/146. life-threatening bleeding in a case of autoantibody-induced factor vii deficiency. A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were < 1.0% of normal. Although an equal part of normal plasma was added to the patient's plasma, PT was not corrected. The patient's plasma inhibited F.VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody. ( info) |
| Congenital factor vii deficiency is a rare disorder associated with reduced levels of Factor VII activity. Replacement therapy is necessary to control hemorrhaging or if surgery is needed. We report operative treatment of one case of chronic abdominal aortic aneurysm in a patient affected by a severe form of congenital factor vii deficiency (endogenous FVII level <1%). The operation was carried out after the administration of Factor VII concentrate raised the Factor VII concentration to hemostatic levels. The patient continued to receive the concentrate every 6 hrs during the first three postoperative days. Dosage was assessed to obtain Factor VII levels not lower than 25%. No postoperative bleeding or thrombotic events were observed. The patient was discharged in excellent condition. ( info) |
| The liver is the primary site of synthesis for the majority of coagulation factors. There are published accounts of liver donor-to-recipient transmission of protein c deficiency with dysfibrinogenemia and factor xi deficiency. In this article, we report what we believe to be the first observation, of transmission of factor vii deficiency, a rare, autosomal recessive coagulation disorder, from an affected liver donor to a naive liver recipient. At 300 days after transplantation, the recipient remains with an isolated prolongation of the prothrombin time and a below-normal level of factor VII, and has had no bleeding complications. ( info) |
| factor vii deficiency is a rare hereditary coagulation disorder with an incidence estimated at 1 in 500,000 individuals. In this report, we describe the 13th case in pregnancy. The diagnosis of severe factor vii deficiency (factor VII level <5%) was established at 10 weeks' gestation after initial laboratory testing showed a markedly prolonged prothrombin time and a normal activated partial thromboplastin time. There was a history of two preterm deliveries, but there was no evidence of previous bleeding manifestations. Antenatal progress of the index pregnancy was unremarkable. Prophylactic treatment with fresh frozen plasma was started at the onset of labor and the patient had a vaginal delivery of a live girl at 36 weeks' gestation. There was no postpartum hemorrhage and mother and newborn were discharged in good condition. The patient's postpartum level of factor VII remained undetectable. Two aspects are outlined: the absence of any significant increase in factor VII clotting activity during this pregnancy and the need to give replacement therapy at labor in patients with severe factor VII deficiency to decrease the risk of postpartum hemorrhage. ( info) |
5/146. Mechanism underlying factor vii deficiency in Jewish populations with the Ala244Val mutation. We investigated a Sephardic Jewish patient with a mild bleeding diathesis whose plasma levels of factor VII coagulant activity and factor VII antigen were 7% and 9% of normal, respectively. Sequencing demonstrated homozygosity for the Ala244Val mutation and the Arg353Gln polymorphism, which is associated with a modest decrease in factor VII levels. To elucidate the mechanism by which Ala244Val reduced factor VII levels in this patient, transient transfections were performed in COS-1 cells with wild type and mutant factor VII cDNAs and factor VII antigen levels in cell lysates and conditioned media were measured. The secretion of the mutant protein (FVII244V) into the media was 20% of wild type (FVIIwt), and intracellular levels of FVII244V were 60% of FVIIwt. A construct encoding Ala244Val along with the Arg353Gln polymorphism decreased the factor VII level in the media to that observed in the patient's plasma. pulse-chase experiments demonstrated that FVII244V did not accumulate intracellularly and that low levels of the abnormal protein were maintained throughout the chase. To test the hypothesis that FVII244V results in an unstable molecule, amino acids with smaller (Gly) or larger (Phe) side chains were substituted for Val244 by site-directed mutagenesis. Transient transfection assays with these constructs demonstrated that the side chain of amino acid 244 is crucial in maintaining a proper conformation of the molecule. We conclude that Ala244Val results in a factor VII molecule that is unstable and is probably degraded intracellularly. ( info) |
6/146. Clinical efficacy and recovery levels of recombinant FVIIa (NovoSeven) in the treatment of intracranial haemorrhage in severe neonatal FVII deficiency. The use of replacement FVII is critical to the successful treatment of life-threatening bleeds in newborns and infants with severe FVII deficiency (<1%). However, the clinical efficacy, optimum dosage and pharmacologic recovery of rFVIIa in such children has not been studied systematically. This report is a case of an infant with severe FVII deficiency (FVII:C at 0%) and massive intracranial haemorrhage in which successful use of rFVIIa (NovoSeven) was carefully monitored. The drug was administered by intravenous bolus through a central line every 4 h at each of three dose levels: 15 microg kg-1, 22 microg kg-1 and 30 microg kg-1. FVII:C was >100% between 30 and 180 min after each infusion with mean trough levels above 25% for all three dose levels. There was no evidence of hyper-coagulation as indicated by measurements of the platelet count, D-dimer, plasma protamine paracoagulant and fibrinogen levels in spite of high FVII:C concentration. In this infant, rFVIIa was well-tolerated, maintained effective haemostasis with good clinical outcome, and produced consistent therapeutic mean trough levels above 25% FVII:C even at 15 microg kg-1 every 4 h. ( info) |
7/146. Combined factor V and factor vii deficiency due to an independent segregation of the two defects. A patient with combined factor V and factor vii deficiency is described together with a family study. The propositus appeared to be double heterozygous for factor V and factor vii deficiency. Since the patient showed a parallel decrease of activity and antigen, he appeared to be double heterozygous for a true deficiency. The patient had inherited the factor V defect from the mother and the factor VII defect from the father. The parents of the propositus were not consanguineous. Other family members were found to have isolated factor V or factor vii deficiency. This is the third family so far described with this peculiar combined defect but the first to be investigated by clotting and immunologic assays. ( info) |
| Factor VII is a vitamin k-dependent zymogen that plays a key role in the initiation of the extrinsic pathway. A severe factor vii deficiency was identified in a 45-year old male whose plasma factor VII antigen was less than 60 ng/ml and expressed 5.2% of normal factor VII activity. dna sequence analysis of the patient's factor VII gene showed a thymidine to guanine transversion at nucleotide 10968 in exon VIII that results in a novel amino acid substitution of His348 to Gln. The patient was homozygous for this mutation, whereas some of his family members were heterozygous. Both wild type and mutant factor VII were transiently expressed in COS-1 cells. The level of secreted mutant factor VII antigen was only 11.0% of the level of wild type factor VII. In cho cells stably transfected with the mutant factor VII, only 37.3% of the total labeled FVII was secreted into the conditioned media and the remainder was retained inside the cells. These data suggest this mutation leads to factor vii deficiency due to the impaired secretion of the molecule. ( info) |
9/146. Successful use of recombinant VIIa (Novoseven) and endometrial ablation in a patient with intractable menorrhagia secondary to FVII deficiency. menorrhagia is a well-recognized complication of inherited bleeding disorders. In the past, the only viable option for women who were unresponsive to medical therapy was hysterectomy. Endometrial ablation has been recently developed as an alternative therapy for these patients and is associated with decreased morbidity. We report the successful use of activated recombinant factor VII (FVIIa) and endometrial ablation in the treatment of excessive menstrual blood loss in a 34-year-old women with severe factor VII (FVII) deficiency. Recombinant FVIIa (40 microg/kg) was administered pre-operatively and every 6 h (20 microg/kg) for 24 h postoperatively. The procedure was uncomplicated with a 200 ml surgical blood loss. FVIIa was used because it allowed FVII replacement with a recombinant product and also has the ability to bind to tissue factor expressed at the site of vascular injury, resulting in site-specific thrombin generation. We believe that endometrial ablation with recombinant VIIa should be considered in patients with severe FVII deficiency and menorrhagia unresponsive to medical therapy. ( info) |
| A clinical syndrome represented by the association of mycobacterium avium complex (MAC) infection with initiation of highly active antiretroviral therapy (HAART) has been recently described in patients with advanced HIV disease. HAART-associated improvement of the immune status might convert a clinically silent MAC infection into an active mycobacterial disease. A 40-year-old man with severe factor vii deficiency, advanced hiv-1 disease, a CD4 lymphocyte count of 15 cells microL-1 (CDC stage A3) and 470,000 HIV-rna copies mL-1 (measurement by NASBA system) underwent standard HAART (lamivudine, stavudine and ritonavir). Two weeks after HAART onset, the patient developed enlargement of the lymph nodes throughout the mesentery and after seven weeks a rapidly enlarging mass on the left side of the neck. culture from a needle aspirate specimen revealed MAC. His CD4 count had increased to 97 cells microL-1 and viraemia dropped to undetectable HIV-rna copies. While continuing antiviral therapy, multidrug therapy for MAC infection (clarithromycin, ciprofloxacin, ethambutol, amikacin) was started with progressive improvement and cure of the neck mycobacterial infection and disappearance of the abdominal lymph nodes. HAART has been shown to offer significant clinical and laboratory benefits in terms of HIV disease with limited side-effects in Haemophiliacs. However, the clinical manifestation of an opportunistic infection should be mentioned as a possible complication of HAART in these patients, as well as in other categories of HIV infected patients, and in patients with congenital coagulopathies. ( info) |