Long-Term Fvii Substitution in a Preterm Infant With Severe Gastrointestinal Bleeding and Fvii Deficiency Due to a Homozygous Donor Splice Mutation Ivs4+1g→A

Abstract

Congenital FVII deficiency is a rare bleeding disorder. Clinical complications are similar to those seen in hemophilia A, and an increased incidence of intracerebral hemorrhage related to birth trauma has been reported. The authors report on an infant who presented at the second day of life with melaena and hematemesis caused by congenital FVII deficiency with minimal activity of 4%. A homozygous mutation IVS4+G-->A, formerly described in 2 siblings, who died of brain hemorrhage within the first month of life, was identified. Severe bleeding events were prevented with prophylactic treatment. Early identification of the underlying mutation helps to assess the risk of hemorrhage and prevent severe bleeding by prophylactic FVII therapy.

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER)

“…Prophylaxis should, therefore, be proposed (possibly within the frame of a prenatal diagnosis program) to those families who already have an affected child bearing a "null" F7 gene lesion associated with severe bleeding. 35,36 In addition, early prophylaxis should be started in severely affected children when central nervous system and gastrointestinal bleeding episodes occur. We have recently published a paper on the treatment of "spontaneous" bleeding episodes in FVII deficiency and found that "on-demand" treatment of these severe bleeds is a suboptimal therapeutic choice.…”

A review of long‐term prophylaxis in the rare inherited coagulation factor deficiencies

“…Long‐term prophylaxis There are 12 case series totalling 31 patients [57,60–70]. Three patients received a PCC [63,67,70], nine received FFP [57,62,69], 10 received FVII concentrate [63,65–67,69,70] and 20 were given rFVIIa [60,61,63–65,67,68,70]. No inhibitor development or thrombotic complications were reported with any product.…”

Long‐term prophylaxis in severe factor VII deficiency

“…One hundred forty-eight articles were found. An accurate selection of all these papers (based on titles, abstract and reading in some cases) identified 16 case stories/series and one review about long-term prophylaxis in FVII deficiency published between 1995 and 2014 [9,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Table 1 summarizes patients characteristics and specific prophylactic regimens.…”

“…Few data are available in the literature regarding long-term prophylaxis in FVII deficiency. The current review of the literature retrieved data regarding 74 patients, treated with regimens that were highly heter-ogeneous [9,11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The indication for long-term prophylaxis was predominantly CNS bleeding followed by haemarthrosis and GI bleeding.…”

“…The molecular analysis of FVII gene showed compound heterozygosity for the following FVII gene genetic variants: c.430+1G>A, c.805+7A>G and p.Thr419Met (c.1256C>T) (nomenclature according to the Human Genome Variation Society instructions; www.hgvs.org/mutnomen). The splice site mutation, c.430+1G>A, has been previously reported in homozygote state associated with severe GI bleeding and brain haemorrhage [19]. The p.Thr419Met mutation was associated in the literature with moderate bleeding tendency: epistaxis, spontaneous haemarthrosis, easy brusing and haematomas [27,28].…”