1/22. 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.- - - - - - - - - - ranking = 1keywords = intracranial haemorrhage, haemorrhage (Clic here for more details about this article) |
2/22. factor vii deficiency in a patient with retinal arteriolar tortuosity syndrome.PURPOSE: To report a pedigree with hereditary retinal arteriolar tortuosity with macular haemorrhage and abnormality of the coagulation system. methods: Case report and literature review. RESULTS: A 49-year-old woman was referred due to macular haemorrhage in both eyes. Her 16-year-old son had recurrent retinal haemorrhages which presented at age 16 years and had mild retinal arteriolar tortuosity. Coagulation studies in the son revealed normal activated partial thromboplastin time (APTT), prolonged prothrombin time (PT) and 30% activity of factor VII. CONCLUSIONS: factor vii deficiency may aggravate the haemorrhages in retinal arteriolar tortuosity syndrome. We therefore suggest conducting routine coagulation studies (PT, APTT) in all patients with retinal arteriolar tortuosity syndrome. Determination of factor VII activity is warranted only in patients with normal APTT and prolonged PT.- - - - - - - - - - ranking = 0.062012049710732keywords = haemorrhage (Clic here for more details about this article) |
3/22. Isolated factor vii deficiency diagnosed after a life-threatening brain haemorrhage.A 65-year-old man was admitted to another hospital with a life-threatening brain haemorrhage, and laboratory examinations on admission revealed prolonged prothrombin time with normal activated partial thromboplastin time. To establish the cause of his abnormal coagulation, he was referred to our clinic. Neither the patient nor his family had any previous history of bleeding symptoms. His liver function was within normal limits but coagulation tests showed increased plasma activities of factors II, VIII, IX, X, with reduced activities of factors V and VII. The activity of factor VII was less than 2% but no inhibitor of factor VII was detected in the plasma. We concluded that the patient had a rare congenital isolated factor vii deficiency although he had not shown earlier bleeding problems, presumably because of compensation for the factor vii deficiency by enhanced activities of components of the extrinsic coagulation pathway, factors II, VIII, IX and X.- - - - - - - - - - ranking = 0.077599632800221keywords = haemorrhage, brain (Clic here for more details about this article) |
4/22. Severe factor vii deficiency with recurrent intracranial haemorrhages owing to double heterozygosity for a splice site mutation of an IVS4 and a novel nonsense mutation in exon 8 (Gln211-->Term).Genetic analysis of a 10-month-old Japanese baby boy with recurrent intrathoracic bleeding, cerebral haemorrhages and gastrointestinal bleeding secondary to severe factor VII (FVII) deficiency revealed evidence of two distinct mutations of FVII: a splice site mutation of G-->A at nucleotide 6071 in the IVS4 splice site and a novel nonsense mutation (Gln211-->Term) in exon 8. His bleeding was difficult to control without prophylactic infusion of FVII. We detected a heterozygous splice site mutation of the IVS4 in his mother and a heterozygous nonsense mutation in exon 8 (Gln211-->Term) in his father. The parents' FVII levels are both 50% of normal controls. The FVII:C in plasma from the proband was < 1.5% of normal controls. FVII:antigen (Ag) was < 1% of normal controls, using a monoclonal antibody (mAb) hVII-B101/1 that specifically reacts with FVII epidermal growth factor 1 (EGF-1), and 5% of normal controls, using a rabbit polyclonal antibody against human FVII. After immunoadsorption with mAb hVII-B101/B1-sepharose 4B, FVII levels of both the proband and his mother were 5% of normal controls; after immunoadsorption the FVII levels of normal subjects were < 1%. We hypothesize that secretion of a small amount of dysfunctional FVII lacking EGF-1 into the circulation accounts for this observation.- - - - - - - - - - ranking = 0.81550301242768keywords = intracranial haemorrhage, haemorrhage (Clic here for more details about this article) |
5/22. Characterization of two novel splice site mutations in human factor VII gene causing severe plasma factor vii deficiency and bleeding diathesis.The molecular basis of severe type I factor (F)VII deficiency was investigated in two Algerian patients. One patient, a 13-year-old-girl who has suffered from severe bleeding since birth, was homozygous for a 7-bp deletion (nt 7774-7780) and a 251-bp insertion (nt 7773-7781) of mitochondrial origin, in IVS 4 acceptor splice site. The other patient, an infant who died from massive intracranial haemorrhage, was homozygous for a transversion in the IVS 7 donor splice site (T9726 2-->G) and a missense mutation in exon 8 (G10588-->A; Arg224-->Gln). In both cases, the deleterious mutations are probably the splice site junction abnormalities impairing mRNA processing. These three lesions have not yet been reported.- - - - - - - - - - ranking = 0.2keywords = intracranial haemorrhage, haemorrhage (Clic here for more details about this article) |
6/22. Experience with use of recombinant activated factor VII.Recombinant activated factor VII (rFVIIa) has recently been introduced for improving haemostasis in haemophiliac patients developing alloantibodies (inhibitors) to factor viii (FVIII) or factor ix (FIX). We describe the successful management of haemorrhagia with rFVIIa in five different situations: an episode of surgical bleeding in a patient with haemophilia A and non-surgical haemorrhages in four patients with haemophilia A, acquired haemophilia, congenital severe FV defect and pseudo-acquired haemophilia, respectively. In each case, rFVIIa was effective and safe. There is no doubt that rFVIIa is useful in the therapeutic management of patients with antibodies to FVIII or FIX. However, the treatment is expensive and a cost-effectiveness analysis would be useful.- - - - - - - - - - ranking = 0.015503012427683keywords = haemorrhage (Clic here for more details about this article) |
7/22. Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor vii deficiency, one of them revealing a new nonsense mutation (Ser52Stop).Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.- - - - - - - - - - ranking = 0.27751506213841keywords = intracranial haemorrhage, haemorrhage (Clic here for more details about this article) |
8/22. Severe FVII deficiency caused by a new point mutation combined with a previously undetected gene deletion.A 3-week-old Caucasian female presented with severe unprovoked parenchymal cerebral haemorrhage. Her plasma factor VII (FVII) activity was <0.01 units/ml. FVII activities for her mother and sister were 0.65 units/ml and 0.51 units/ml, respectively, while her father's level was normal. These results indicated that the mother was heterozygous for a non-functional F7 gene that had also been inherited by the proband's sister. The proband's severe FVII deficiency was caused by a new mutation in her paternal F7 gene coupled with the inheritance of the non-functional maternal F7 gene. dna sequence analysis revealed that the proband had apparent homozygosity for a novel single point mutation (g.3907G >A) changing the codon for Glu29 to Lys (E29K); neither parent had the E29K mutation. Because of the unlikelihood that the proband was homozygous for two identical new point mutations, the dna sequence abnormality was more likely to have arisen from a single mutated gene on one allele and a F7 gene deletion on the other allele. Real time polymerase chain reaction (PCR) analysis confirmed that the proband had inherited a gene deletion that was present in the maternal side of the family. Subsequent clotting assays and real time PCR revealed that the maternal deletion also included the closely linked F10 gene.- - - - - - - - - - ranking = 0.015503012427683keywords = haemorrhage (Clic here for more details about this article) |
9/22. Congenital factor vii deficiency: a case report.factor vii deficiency is a rare congenital blood disorder. Its clinical features are rather variable and ranges from epistaxis to massive intracranial haemorrhage. Treatment involves replacement therapy, which constitutes use of fresh frozen plasma, prothrombin complex concentrates or recombinant activated factor VII. Although it is a rare entity, one still needs to consider it as a probable diagnosis in a newborn with coagulopathy. We report here a case of factor vii deficiency in a newborn who presented with subdural haemorrhage at day 4 of life.- - - - - - - - - - ranking = 0.21550301242768keywords = intracranial haemorrhage, haemorrhage (Clic here for more details about this article) |
10/22. Factor VII inhibitor.Acquired inhibitors of blood coagulation factors occur spontaneously or secondarily to various diseases or drug administration. A clinically significant factor VII inhibitor is very rare. We report a patient developing factor VII inhibitor possibly as a reaction to penicillin administration; it gave rise to fatal haemorrhage.- - - - - - - - - - ranking = 0.015503012427683keywords = haemorrhage (Clic here for more details about this article) |
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