Factor XI replacement for inherited factor XI deficiency in routine clinical practice: results of the HEMOLEVEN prospective 3-year postmarketing study.

Factor XI (FXI)-deficient patients may develop excessive bleeding after trauma or surgery. Replacement therapy should be considered in high-risk situations, especially when FXI levels are below 20 IU dL(-1) . HEMOLEVEN is a human plasma-derived factor XI concentrate available in France since 1992, but there are few data regarding its use by physicians. This prospective study assessed the use, efficacy and safety of HEMOLEVEN in common clinical practice. HEMOLEVEN was evaluated in FXI-deficient patients in 13 French centres in a 3-year postmarketing study. Forty-four patients (30 females, 14 males) received 67 treatments. The median age was 37 years (8 months-91 years). Basal FXI levels were <1 to 51 IU dL(-1) (median: 5.5); 29 patients were severely FXI-deficient (<20 IU dL(-1) ). FXI was administered prophylactically before 43 surgical procedures, 10 invasive procedures, 8 vaginal deliveries, or as curative treatment for six bleeds. The efficacy was assessed as excellent/good in 63, moderate in two and undetermined in two treatments. Seven patients experienced seven adverse effects, including two rated as serious: one sudden massive pulmonary embolism with fatal outcome and one case of inhibitor to FXI. HEMOLEVEN is effective for bleeding prevention in FXI deficiency. However, considering the benefit/risk ratio observed in relation to dosage in this study; firstly, it should be used sparingly due to its potential prothrombotic effect; secondly, new prescription procedures should be defined to adapt the dosage, especially in patients with intrinsic and/or acquired risk factors for thrombosis.

Treatment of severe von Willebrand disease with a high-purity von Willebrand factor concentrate (Wilfactin): a prospective study of 50 patients.

BACKGROUND AND OBJECTIVES: A plasma-derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. METHODS AND RESULTS: Fifty patients with clinically severe VWD (72% had VWF ristocetin cofactor activity less than 10 IU dL(-1) and 46% had FVIII < 20 IU dL(-1)) were treated with the concentrate as the only therapy, except for clinical situations requiring a priming dose of FVIII to rapidly correct an intrinsic coagulation defect. A total of 139 spontaneous bleeding episodes were treated; only 53 (38%) needed a concomitant FVIII dose. Outcome was excellent or good in 89% of the episodes. Forty-four patients underwent 108 surgical or invasive procedures. Outcome was excellent or good in 95 scheduled procedures (only VWF was infused) and 13 emergency procedures (a priming FVIII dose was co-administered with the first VWF infusion). There were no thrombotic complications and none of the 18 patients with type 3 VWD developed anti-VWF or anti-FVIII antibodies. CONCLUSIONS: This concentrate safely and effectively provides hemostasis in patients with clinically severe VWD.

Partial characterization of a fatty acid desaturase gene in Drosophila melanogaster.

The open reading frame of a gene encoding a protein homologous to vertebrate fatty acid desaturases has been characterized in Drosophila melanogaster. This is the first description of a desaturase sequence in insects. Two cDNAs were cloned: the combined 1.5 kb nucleotide sequences indicate that the gene encodes a polypeptide of 383 amino acid residues with a high sequence similarity to the well defined delta 9 desaturases from rat and yeast and desaturases from carp and tick. The Drosophila protein contains two histidine cluster motifs (HXXHH) and two hydrophobic regions which are conserved among all desaturases, whereas the amino and carboxy ends look more variable. The desaturase gene seems to be expressed in adults at a low level, with a greater prevalence in females than in males. Two genomic sequences have been amplified by polymerase chain reaction (PCR), and have a very similar open reading frame but a different organization; one with three introns and the other without introns. Both seem to correspond to two distinct genes and have been named "desat locus". They are localized to a single locus, 87C, on the right arm of the third chromosome. The possible involvement of the desat product in the biosynthesis of D. melanogaster contact pheromones is discussed.