Levels of prothrombin activation peptide F1+2 in patients with a bleeding tendency.

Numerous recent publications point to significant improvements in haemostasis in the bleeding patient suffering from haemophilia with inhibitors when a recombinant activated factor VII (rFVIIa) molecule is administered in high doses. In theory, activated factor VII (FVIIa) is believed to initiate haemostasis through its physiological interaction with tissue factor at sites of cellular injury, whereby factor X (FX) activation and, in consequence, thrombin formation is amplified. There has been speculation, however, whether high circulating FVII procoagulant (FVII:C) levels may induce systemic coagulation activation.

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days.

Efficacy and safety of continuous infusion of Mononine during five surgical procedures in three hemophilic patients.

We report here five surgeries successfully performed with a continuous infusion of Mononine (Armour Pharmaceutical Company, Kankakee, IL) in three hemophilic B patients. Before surgery the patients received a bolus dose of 40 to 100 U/kg according to the type of surgery. This injection was followed by a continuous infusion of Mononine, with an infusion rate of 3.

Illegitimate transcription: its use for studying genetic abnormalities in lymphoblastoid cells from patients with Glanzmann thrombasthenia.

Glanzmann thrombasthenia is the most common inherited disorder of platelets that may induce severe bleeding complications. Molecular biology techniques have offered the possibility to assess the basis of this chronic haemorrhagic disease at the molecular level. However, the accessibility of mRNA in platelets is limited by the availability of the patient's blood samples and the relatively weak amount of this material in these cells.

The treatment of bleeding in acquired haemophilia with recombinant factor VIIa: a multicentre study.

Recombinant factor VIIa was used to treat 38 patients with acquired haemophilia participating in the Novoseven compassionate-use program. 19 were male, median age 59, range 2-89 years. The median pre-treatment anti-human (H) and anti-porcine (P) inhibitor titre was H 43 BU/ml (range 1-4500) and P 4.

Phase I study of interleukin-6 in children with solid tumours in relapse.

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg.

Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity.

Factor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers.

A nonsense mutation in the GPIIb heavy chain (Ser 870-->stop) impairs platelet GPIIb-IIIa expression.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, caused by a quantitative or qualitative defect of the GPIIb-IIIa integrin (alpha IIb beta 3), which functions as the platelet fibrinogen receptor. We report a case of type I GT due to a homozygous mutation resulting in Ser 870 to stop codon substitution. This residue is located near the proteolytic cleavage site of proGPIIb.

Combined hereditary disorders of haemophilia B Leyden (-6 G-->A) and type 1 von Willebrand disease.

Multiple coagulation disorders are unusual. We report here a combination of haemophilia B Leyden with type 1 von Willebrand disease (vWD) affecting different members of the same family. Haemophilia B Leyden was due to a -6 G-->A mutation within the promoter of the factor IX gene and was responsible for a mild haemophilia in the father of the proband.

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns.

Molecular study of Glanzmann thrombasthenia in 3 patients issued from 2 different families.

In an effort to further understand Glanzmann thrombasthenia (GT) 3 patients from 2 different families were studied. After biochemical and immunological analysis these patients were classified as type I. We observed in the first family a new restriction site for Stu I in exon II of the glycoprotein (GP) IIIa gene caused by a homozygous nonsense mutation: 62 Arg to stop codon.

Combined factor IX and protein C deficiency in a child: thrombogenic effects of two factor IX concentrates.

We have recently described an unusual situation which involved a combination of a factor IX and a protein C deficiency in a young child who presented, according to the bleeding tendency, as a hemophilia B patient. In this particular hemophiliac, baseline prothrombin fragment F1 + 2 levels were unexpectedly elevated and increased after an injection of a very high purity factor IX concentrate. This observation raised a question regarding the substitution schedule in the case of repeated injections of factor IX, since the thrombotic tendency has been a major concern with some factor IX concentrates.

Incidence of factor VIII inhibitor development in severe hemophilia A patients treated only with one brand of highly purified plasma-derived concentrate.

The incidence of factor VIII inhibitor was studied in a cohort of 56 previously untreated patients with severe hemophilia A (factor VIII below 1 U/dl). They received only one brand of highly purified factor VIII concentrate (HPSD-VIII) prepared by conventional chromatography with a solvent-detergent step for viral inactivation. Follow-up since the first infusion of HPSD-VIII was from 1 to 76 months (mean = 29) and cumulative exposure days (CED) from 1 to over 100 (median = 26).

Increased thrombosis incidence in a family with an inherited protein S deficiency and a high oxygen affinity hemoglobin variant.

Inherited protein S deficiency and the presence of a rare high oxygen affinity hemoglobin variant: Hb Rainier [beta 145 (HC2) Tyr-->Cys] were found in a family. Among 16 studied members, nine were found as carriers of protein S deficiency (type I with decrease of total, free, and activity levels). Six subjects carried the high-affinity hemoglobin variant, which displayed an increase of blood viscosity.

Hepatitis A in French hemophiliacs.

The prevalence of serum antibodies to hepatitis A virus (HAV) in 793 hemophilia A (HA) and 89 hemophilia B (HB) patients coming from 10 French Hemophilia Centers and treated since 1986-1987 with solvent/detergent (SD)-treated products is reported. The results indicated seropositivity to HAV of 29.9% in HA and 40.

Increased thrombin generation in a child with a combined factor IX and protein C deficiency.

We report a quantitative protein C deficiency combined with a factor IX deficiency in a one-year-old boy. The inheritance of the two deficiency states was independent, the factor IX defect coming from the mother and the protein C defect from the father. Both factor IX activity and antigen were below 1%, and protein C activity as well as antigen were close to 27% of normal values.

[Thrombosis of superior longitudinal sinus and pulmonary embolism in nephrotic syndrome].

The authors report on the case of a child with the nephrotic syndrome complicated by thrombosis of superior longitudinal sinus, bilateral massive pulmonary embolism resulting in a sudden death. A dramatic deficiency in factor XII was demonstrated; the pathophysiology and management of such an abnormality are discussed.