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S Lethagen

Publications and source records attributed to S Lethagen.

72 records · Page 4Linked to original sources
PubMed1993

Self-treatment with desmopressin intranasal spray in patients with bleeding disorders: effect on bleeding symptoms and socioeconomic factors.

Desmopressin (1-desamino-8-D-arginine vasopressin), an established hemostatic agent for the treatment of bleeding in mild hemophilia A, von Willebrand's disease, or platelet disorders, has mostly been given parenterally as intravenous or subcutaneous injections. Intranasal administration by spray has been shown to yield significant and highly reproducible increases in the plasma concentrations of factor VIII and von Willebrand factor and platelet adhesiveness, and to be suitable for self-administration at home, as it is easy to handle and does not involve the use of needles. This paper presents data from a questionnaire answered by 78 patients with mild hemophilia A, von Willebrand's disease, or platelet disorders, who had used the spray at home to treat bleeding symptoms. The patients experienced decreased blood loss and shortened duration of epistaxis, menorrhagia, tissue bleeding, and bleeding in connection with minor surgery or tooth extraction. The use of factor VIII concentrates was diminished, as were the number of visits to outpatient care and absence from school or work.

Adult↗
PubMed1992

Pharmacokinetics and hemostatic effect of different factor VIII/von Willebrand factor concentrates in von Willebrand's disease type III.

Four different plasma-derived concentrates composed of coagulation factor VIII (FVIII) and von Willebrand factor (vWF) of varying quality (Hemate-P, Behring; Profilate, Alpha; and F VIII-VHP-vWF, C.R.T.S Lille), or almost purified vWF (Facteur Willebrand, C.R.T.S Lille) and one recombinant F VIII concentrate (Recombinate, Baxter) were given, in doses of 30-60 IU VIII: C/kg or 70-110 IU RCof/kg, to five patients with von Willebrand's disease type III, in order to evaluate the role of the vWF in factor F VIII concentrates. All plasma concentrates except Profilate had a multimeric vWF pattern almost similar to that of normal plasma. Bleeding time (b.t.), VIII: C, vWF:Ag, ristocetin cofactor activity, and multimeric pattern of the plasma-vWF were followed for 72 h. Both Duke b.t. and the multimeric pattern in plasma normalized after infusion of Hemate-P, F VIII-VHP-vWF, and Facteur Willebrand and, to a lesser extent, after Profilate. As expected, in response to Recombinate there was no effect on primary hemostasis, and the half-life of F VIII procoagulant activity (VIII: C) was very short. Normalization of the vWF is important not only for improving the primary hemostasis, but also for maintaining the plasma F VIII concentration on a high level, both by reducing the elimination rate of infused F VIII and via a secondary release of endogenous F VIII. If a prompt hemostatic effect is required, we recommend a concentrate containing both F VIII and all vWF multimers, but for prophylactic treatment, pure vWF may be used.

Adult↗
PubMed1992

DDAVP-induced enhancement of platelet retention: its dependence on platelet-von Willebrand factor and the platelet receptor GP IIb/IIIa.

Although DDAVP has been shown to be haemostatically efficacious in patients with various congenital or acquired platelet disorders, no reasonable explanation has been found for this effect. We have previously shown DDAVP to increase platelet adhesiveness as measured with a platelet retention test. The aim of the present study was to investigate the mechanism of action responsible for the increased platelet retention in response to DDAVP. Patients with vWD type III and type Ia, severe haemophilia and severe thrombasthenia, as well as healthy controls, were included in the study. The effect of different concentrations of vWF in plasma and platelets was explored, as was the effect on platelet function of apyrase and monoclonal antibodies against GP IIb/IIIa and GP Ib. We found the effect of DDAVP on platelet retention to be unaffected by changes in the plasma concentration of vWF. The enhanced platelet retention after DDAVP is apparently dependent on the presence of platelet-vWF and on a normal function of the GP IIb/IIIa. The effect is not mediated via ADP or thrombin. The platelet-stimulating effect of DDAVP may be one explanation for the positive haemostatic effect in patients with certain platelet disorders.

Adolescent↗
PubMed1992

Laparoscopic cholecystectomy in a patient with hemophilia B.

Surgical procedures in hemophiliacs is a demanding challenge for the surgeon and hematologist. This report deals with a successful laparoscopic cholecystectomy in a young patient with hemophilia B. Despite a prolonged operation time, because of a partially intrahepatic gallbladder, no bleeding complications were registered and the patient recovered well. Laparoscopic cholecystectomy seems to be the method of choice in hemophiliacs, as it minimizes tissue trauma. Nevertheless, the procedure should be performed only in specialized centers with a fully equipped coagulation laboratory and a team of surgeons and hematologists familiar with the special problems of surgery in hemophiliacs.

Adult↗
PubMed1991

Blood loss and safety with desmopressin or placebo during aorto-iliac graft surgery.

In a double blind, placebo controlled study in 50 patients undergoing aorto-iliac graft surgery, we studied the effects of desmopressin given prior to surgery on blood loss and blood transfusion requirements. Desmopressin reduced the number of patients with clinically significant bleeding. Blood loss volumes and transfusion requirements were lower in the desmopressin group, but this could not be verified statistically. Even if our study population has a high incidence of generalised arteriosclerotic disease, there were no clinical manifestations of venous thromboembolism, no increase of graft occlusions and no myocardial infarction during the operative or early postoperative period. Desmopressin may be used in patients with excessive peroperative bleeding or a prolonged preoperative bleeding time. In patients where desmopressin is considered to be haemostatically efficacious, it may be used with a maintained margin of safety.

Aorta, Abdominal↗
PubMed1990

Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand's disease type I.

Desmopressin acetate (1-desamino-8-D-arginine vasopressin, DDAVP) has mostly been given by the parenteral route for the treatment of mild hemophilia A and von Willebrand's disease type I. In the present study the hemostatic effects of desmopressin acetate administered intranasally by spray in a dose of 300 micrograms and intravenously 0.3-0.4 micrograms/kg were assessed and compared in 8 patients with hemophilia A and 22 patients with von Willebrand's disease type I. A bioequivalent response to intravenous and intranasal desmopressin acetate was found in Factor VIII coagulant activity (VIII:C) in the hemophilia patients. In the von Willebrand patients, an equivalent shortening of the bleeding time was seen after the two modes of administration, even though intravenous injection gave a higher increase in plasma levels of VIII:C and vWF:Ag. In five patients with von Willebrand's disease the duration of the spray effect on VIII:C and vWF:Ag was followed for 24 h. After 12 h the mean level of VIII:C was 1.4, and of vWF:Ag 1.5, times the basal level. The findings suggest that the spray can be recommended for home or prophylactic treatment of patients with mild hemophilia A and von Willebrand's disease.

Administration, Intranasal↗
PubMed1990

Effects of desmopressin acetate (DDAVP) and dextran on hemostatic and thromboprophylactic mechanisms.

The effects on hemostatic and thromboprophylactic mechanisms of intravenous desmopressin (DDAVP, 0.3 micrograms/kg) and dextran 40 and 70 given both separately and in various combinations were evaluated in five male volunteers. Dextran did not inhibit the DDAVP-induced hemostatic changes. The dextran-induced decrease in platelet adhesiveness and the prolonged bleeding time were totally reversed by DDAVP. Hematocrit decrease was seen after both drugs, lasting longer when they were combined. We conclude that DDAVP and dextran may be used concomitantly, each with maintained beneficial properties. DDAVP will still act hemostatically by increasing platelet adhesiveness, factor VIII and von Willebrand factor and by shortening the dextran-induced prolongation of bleeding time. Dextran and DDAVP may even have additive antithrombotic effects due to the DDAVP-induced stimulation of the fibrinolytic activity, which is not inhibited by dextran, and to rheologic changes such as hematocrit decrease induced by both drugs.

Adult↗
PubMed1989

Effect of viscosity on the pharmacokinetics and biological response to intranasal desmopressin.

The effect of viscosity on the nasal absorption and biological response to desmopressin was studied in humans. Nasal solutions of desmopressin with and without the addition of 0.25% (w/v) methylcellulose were administered by a precompression nasal spray pump to 10 volunteers. Plasma levels of desmopressin were assayed by radioimmunoassay and the biological response was measured by determination of the antihemophilia factors (Factor VIII and von Willebrand factor). The results showed that the addition of methylcellulose produced a more sustained and slower absorption, with a longer time to maximum plasma concentration (tmax). However, the areas under the plasma concentration-time curve were not different, indicating a similar total bioavailability. The biological response showed a similar effect. Peak Factor VIII activity was not different, but the presence of methylcellulose produced a slower onset of activity. These findings indicate that although the addition of a viscous agent to nasal formulations may produce a more sustained effect, it delays the onset of activity and no enhancement is achieved in the total bioavailability.

Administration, Intranasal↗
PubMed1988

Effects of concentration and volume on nasal bioavailability and biological response to desmopressin.

The effects of concentration and dose volume on the nasal bioavailability and biological response to desmopressin [DDAVP; 1-(3-mercaptoproprionic acid)-8-D-arginine vasopressin] were investigated in humans. A nasal formulation of 300 micrograms of desmopressin was administered using a premetered spray device in doses of either 1 x 50-, 2 x 50-, or 1 x 100- microL actuations to both nostrils. Intravenous administration of 0.2 micrograms/kg was also given as a reference for bioavailability calculations. Plasma levels of desmopressin were measured by radioimmunoassay. The biological response was determined by measuring circulating levels of Factor VIII (F VIII), the antihemophilia factor. Peak plasma levels of desmopressin were greatest after the 2 x 50-microL dose, followed by the 1 x 50- and 1 x 100-microL doses. The bioavailability of desmopressin from the 2 x 50-microL dose was 20%, which was significantly greater than the 11% after the 1 x 50-microL (p less than 0.01) and 9% after the 1 x 100-microL (p less than 0.001) doses. The biological response was clearly enhanced after the 2 x 50-microL dose compared with the 1 x 50- and 1 x 100-microL doses. The interindividual response in F VIII levels to nasal desmopressin ranged from 20 (CV) to 30%, which compared favorably with the 36% variation after intravenous administration. This study confirms the premetered spray device as the preferred intranasal drug delivery system, and shows that by optimizing concentration, volume, and technique of administration, a significant enhancement can be obtained in bioavailability and clinical efficacy.

Administration, Intranasal↗
PubMed1988

Effect of viscosity on particle size, deposition, and clearance of nasal delivery systems containing desmopressin.

The effect of methylcellulose on the particle size distribution and dosing accuracy of pre-metered spray pump devices containing the peptide desmopressin (DDAVP) was investigated. Using gamma scintigraphy, the influence of methylcellulose on the in vivo deposition and clearance of nasal solutions administered as drops or spray was studied. Nasal formulations containing 0, 0.25, and 0.50% methylcellulose produced a dose-related increase in average particle size from 51 micron for 0% to 81 and 200 micron for 0.25 and 0.50% methylcellulose, respectively. However, no effect was observed on the dosing accuracy of the spray pumps. The addition of methylcellulose gave a more localized in vivo deposition in the anterior region of the nasal vestibule. However, the net effect on clearance followed a biphasic pattern which showed an increase in retention time for the 0.25% solution, followed by a decrease in retention time and faster clearance time for the 0.50% solution. The spray delivers well-controlled doses to the nasal cavity. These findings show that viscosity, particle size, and nasal clearance are important parameters in the design of nasal delivery systems.

Administration, Intranasal↗
PubMed1987

Intranasal and intravenous administration of desmopressin: effect on F VIII/vWF, pharmacokinetics and reproducibility.

A comparison was made of intranasal administration of 300 micrograms desmopressin (DDAVP) by spray, with intravenous administration of 0.2, 0.3 and 0.4 microgram DDAVP/kg in 10 healthy volunteers. The effect of DDAVP was measured on F VIII/vWF complex and on plasminogen activator release. In addition, plasma levels of DDAVP were determined using a specific and sensitive radioimmunoassay. Moreover, the reproducibility of the spray effect in 10 healthy volunteers was tested after administration of 300 micrograms DDAVP intranasally by spray on 5 different occasions. Plasma levels of DDAVP showed a clear dose-response with the maximum levels at 0.4 microgram/kg i.v. The effect of the spray approximated the 0.2 microgram/kg response. However, the maximum response in both F VIII/vWF complex and plasminogen activator release was obtained after 0.3 microgram/kg i.v. The response to 0.4 microgram/kg i.v. was not significantly different from the response to 0.3 microgram/kg indicating that maximum stimulation was reached with 0.3 micrograms/kg. There was no correlation between plasma levels of F VIII/vWF and DDAVP indicating that the biological response to DDAVP is subjected to saturation kinetics. The reproducibility of the effect of the spray dose on VIII:C was 21% (c.v.) and 27% for the intra-individual and inter-individual variation, respectively, and compared favorably with intravenous administration. Intranasal DDAVP (300 micrograms) is as effective as 0.2 micrograms/kg intravenously and provides an accurate, reproducible and convenient alternative to parenteral administration.

Administration, Intranasal↗
PubMed1986

Clinical application of the chromogenic assay of factor VIII in haemophilia A, and different variants of von Willebrand's disease.

A chromogenic substrate kit for determination of factor VIII activity (COATEST Factor VIII) was compared to a one-stage clotting assay and the correlation was evaluated in different genetic variants of mild and moderate haemophilia A, in severe haemophilia A and in all known variants of von Willebrand's disease. In all these cases a high correlation between the two methods was obtained. A good correlation was also obtained after intranasal administration of DDAVP (1-desamino-8-D-arginine vasopressin) to patients with von Willebrand's disease. The chromogenic substrate method was performed using a microtray technique.

Chromogenic Compounds↗
PubMedDate not supplied

Von Willebrand's disease.

Explore the source record for details and available documents.

Deamino Arginine Vasopressin↗