PubMed Health⌕ Search

Biomedical subjects

S Lethagen

Publications and source records attributed to S Lethagen.

At least 55 records · Page 3Linked to original sources
PubMed1998

The Malmö-Klaipeda WFH twinning programme: a comparative description of the haemophilia cohorts.

In 1994, the Malmö-Klaipeda twinning programme was approved by the World Federation of Hemophilia. One of the first steps in the collaboration has been to set up a registry of the haemophilia patients in the Klaipeda area. In order to collect important clinical data the patients have been examined jointly by experts on haemophilia from the two centres. Seventeen out of 25 patients with severe haemophilia known at the Klaipeda centre were examined and compared to a matched cohort of patients from the Malmö centre. The main differences between the cohorts were that home treatment was not available to the Klaipeda patients, they received less treatment in general, had higher joint scores and more frequent bleeds. The pattern of transmission of blood-borne virus was very similar, with a high prevalence of hepatitis C antibodies. We conclude that the twinning programme between Malmö and Klaipeda has resulted in several achievements, including training of staff and a necessary inventory of the patients. This should not only form a suitable platform for the future development of haemophilia care in Lithuania, but could also serve as an example for liaisons between other haemophilia centres.

Adolescent↗
PubMed1998

Low recurrence rate after deep calf-vein thrombosis with 6 weeks of oral anticoagulation.

OBJECTIVES: To evaluate the recurrence rate after deep calf-vein thrombosis treated with 6 weeks of oral anticoagulation. DESIGN AND SUBJECTS: A 2 year follow-up of 126 consecutive patients admitted to the Department of Internal Medicine with venographically verified deep calf-vein thrombosis. RESULTS: One hundred and twenty-six patients were treated with warfarin for 6 weeks, 18 of them having had a previous episode of venous thrombosis (DVT). Eleven patients (8.7%) suffered a recurrent thromboembolic episode within 2 years, four of which were within the first 3 months. Eight of those without a history of DVT had a recurrence (7.4%). Three of these were activated protein C (APC)-resistant, one was protein C-deficient and one had malignant melanoma. Eight patients (6.3%) reported minor haemorrhagic complications, but no major bleeding was seen. CONCLUSION: Our data support the use of a 6 week regimen of secondary oral prophylaxis after a first episode of deep calf-vein thrombosis in patients without a permanent risk factor. Whether individuals with inherited thrombophilia require prolonged treatment remains to be evaluated.

Administration, Oral↗
PubMed1998

Ins405AsnPro mutation in the von Willebrand factor propeptide in recessive type 2A (IIC) von Willebrand's disease.

The molecular defects of the von Willebrand factor (vWF) have been studied in the patient in whom the von Willebrand disease phenotype IIC was originally described. A six nucleotide insert, AATCCC, was found in exon 11 of the vWF gene, predicting the insertion of the amino acids asparagine and proline between phenylalanine 404 and threonine 405 of the vWF propeptide. The mutation was present in one allele. Analysis of amplification products derived from platelet vWF mRNA showed the other allele to be silent. The patient is thus a compound heterozygote for a null allele and the IIC allele, in accord with the recessive mode of inheritance of the IIC phenotype. Family studies indicated the IIC mutation to have occurred de novo, possibly as a result of a duplication event. In vitro mutagenesis and expression in COS-7 cells confirmed the detrimental effect of the mutation on vWF multimer assembly. Taken together with those of earlier studies the present findings suggest that the IIC phenotype may well be exclusively caused by mutations which result in changes of the amino acid sequence in certain regions of the vWF propeptide. Although in the recently revised classification of von Willebrand's disease variants, the IIC type is included in the 2A category, obviously it constitutes a very distinct subtype.

Animals↗
PubMed1998

Out-patient treatment of acute deep vein thrombosis.

BACKGROUND: To assess whether uncomplicated deep vein thrombosis could be treated in an out-patient setting without increasing the frequency of complications, and to determine the proportion of patients with deep vein thrombosis, traditionally treated as in-patients at the Departments of Medicine, who are eligible for such treatment. METHODS: In a multicentre study, carried out at six hospitals of varying sizes and serving a population of about 600,000, consecutive patients over 18 years of age, with verified deep vein thrombosis, primarily presented as acute cases at the respective Departments of Medicine, were considered for treatment on an out-patient basis during a 1-year period. INTERVENTIONS: Those eligible for out-patient treatment were put on low molecular weight heparin and oral anticoagulants, and scheduled for daily attendance at the out-patient clinic of the respective Dept. of Medicine. Details of any complication were recorded according to a standard check-list. The patients underwent a full checkup at three-month follow-up. MAIN OUTCOME MEASURES: Any bleeding event or pulmonary embolism. Progress of thrombosis. RESULTS: Of 523 patients considered for out-patient treatment, 126 (24%) were excluded according to the defined exclusion criteria, 197 (38%) were treated entirely on an out-patient basis, and another 43 (8%) were initially treated in hospital (median two days) before being transferred to the out-patient setting. Three patients had to be hospitalized for suspected complications, but none of these turned out to be serious. No serious bleeding event or thromboembolic complication was registered. CONCLUSIONS: Uncomplicated acute deep vein thrombosis could be safely treated on an out-patients basis. At least 50% of the patients with this diagnosis, former treated as in-patients at the Depts. of Medicine, are eligible for such treatment.

Acute Disease↗
PubMed1997

The effect of tranexamic acid on local and plasma fibrinolysis during total knee arthroplasty.

The aim of the present study was to investigate aspects of coagulation and fibrinolysis during knee arthroplasties in order to find out. 1. whether an increased fibrinolysis is correlated to an increased blood loss 2. whether there is a difference in markers for coagulation and fibrinolysis in peripheral venous blood compared to those in blood from the wounds 3. whether the administration of tranexamic acid modifies the fibrinolytic response. Twenty-four patients were included. Twelve patients were given tranexamic acid intravenously at the end of the operation. The dose was repeated three hours later. The other 12 patients were given an equivalent amount of placebo. The administration was randomised and double-blind. Levels of prothrombin fragments 1 + 2, D-dimers, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1) in venous blood were investigated just before the operation, at the end of the operation and three hours later. At the end of the operation blood for analysis was also drawn from the wound. Coagulation and fibrinolysis was activated during and after surgery. The activation was significantly higher in blood from the wounds than in peripheral venous blood. We found no direct correlation between the degree of fibrinolysis and blood loss. The administration of tranexamic acid reduced fibrinolysis in the wounds but not in peripheral venous blood. The postoperative blood loss was reduced by half.

Aged↗
PubMed1997

The UK guidelines for the use of desmopressin in patients with von Willebrand's disease. Von Willebrand Working Party of the United Kingdom Haemophilia Centre Director's Organization.

A document entitled Guidelines for the Diagnosis and Management of von Willebrand's Disease was produced by the von Willebrand Working Party of the United Kingdom Haemophilia Centre Directors' Organization. Under the chairmanship of Dr Beverley Hunt, an independent board of haematologists and anaesthesiologists reviewed the use of a synthetic vasopressin analogue, desmopressin (DDAVP), in the management of patients with von Willebrand's disease. The Advisory Board considered that production of the guidelines was to be applauded, but that the contraindications for DDAVP were imprecisely defined and may thus be misleading. This paper summarizes the Advisory Board's discussion of the suggestions.

Deamino Arginine Vasopressin↗
PubMed1997

Desmopressin--a haemostatic drug: state-of-the-art review.

Desmopressin is a well tolerated and convenient haemostatic drug that can be used in a number of clinical conditions with bleeding diathesis. It has several effects on the haemostatic system, causing endogenous release of coagulation factor VIII, von Willebrand factor, tissue plasminogen activator and also increasing platelet adhesiveness and shortening bleeding time. The effect is virtually immediate and lasts for several hours. Side-effects are few and mostly mild. Desmopressin is suitable for home use in selected patients with bleeding diathesis. The optimal dosage is 0.3 microgram kg-1 intravenously, but the drug may also be administered subcutaneously or intranasally. In addition to the established indications, haemophilia A, von Willebrand's disease and platelet dysfunction, the drug may also be used safely in other patients with unexpected bleeding during or after surgery. The effectiveness of general prophylactic use of desmopressin, in order to diminish surgical blood loss and transfusion requirements, has not been proven, except in patients with known bleeding diathesis caused by congenital or acquired haemostatic disorders, e.g. in those taking aspirin.

Deamino Arginine Vasopressin↗
PubMed1997

von Willebrand factor mediates increased platelet retention in recurrent thrombotic thrombocytopenic purpura.

The plasma cryoprecipitate of two brothers with recurrent thrombotic thrombocytopenic purpura (TTP) was previously found to mediate increased platelet retention and contain ultra-large von Willebrand factor (vWF) multimers during remissions. We conducted this study to examine if vWF is involved in the increased platelet retention in TTP. Platelet retention decreased when the patients' plasma was incubated with a monoclonal antibody directed to the vWF epitope which interacts with the platelet receptor glycoprotein Ib or when incubated with a Fab-fragment directed to the platelet receptor glycoprotein IIb/IIIa. Replacement of patient vWF with an equivalent concentration of a factor VIII/vWF concentrate containing no ultra-large vWF multimers was accompanied by a normalization of platelet retention. These results indicate that vWF is involved in the increased platelet retention. Analysis of polymorphic markers in the vWF gene demonstrated that a recessive mutation in this gene is unlikely.

Adolescent↗
PubMed1996

Increased platelet retention in familial recurrent thrombotic thrombocytopenic purpura.

We studied two brothers with recurrent thrombotic thrombocytopenic purpura (TTP). Platelet retention, measured with a modified Adeplat S glass-bead test, was found to be increased during acute episodes of TTP and during remissions. Values of platelet retention ranged between 57 to 95% (normal range 16 to 34%). The continually elevated values enabled us to investigate which fraction of the patients' blood was responsible for the increased platelet retention and to evaluate the effect of different treatments on this parameter. We found that the patients' plasma increased the retention of normal platelets and of platelets taken from a patient with von Willebrand's disease type III. This activity was located in the cryoprecipitate fraction of plasma. Unusually large von Willebrand factor (vWF) multimers were demonstrated in both children during remission and decreased during relapse. Both fresh frozen plasma (FFP) and a commercial factor VIII/vWF concentrate reduced platelet retention when tested during remission. Treatment of both siblings with FFP or factor VIII/vWF concentrate was beneficial during recurrences. We conclude that the elevated platelet retention is due to a factor in the cryoprecipitate of the childrens' plasma, and that both FFP and factor VIII/vWF concentrate are effective in decreasing platelet retention.

Adult↗
PubMed1994

Desmopressin (DDAVP) and hemostasis.

Desmopressin is a widely used hemostatic drug. It is a synthetic analogue of the natural hormone vasopressin, but, in contrast to vasopressin, it has no pressor activity. The effect is immediate, with two- to sixfold increases in the plasma concentrations of coagulation factor VIII, on Willebrand factor, and tissue plasminogen activator, and increases in platelet adhesiveness of comparable magnitude. Desmopressin is used in patients with mild hemophilia A, von Willebrand's disease, congenital platelet dysfunction, or acquired platelet dysfunction due to uremia or intake of such drugs as aspirin. It may also be used to reduce surgical blood loss in patients without known bleeding diathesis. Optimal hemostatic effect is achieved with a dosage of 0.3 micrograms/kg given intravenously. Other routes of administration are subcutaneous injection or intranasal spray. The latter proved to be efficient for home treatment of patients with bleeding disorders.

Administration, Intranasal↗
PubMed1993

Biochemical and in vivo properties of high purity factor IX concentrates.

The purified factor IX concentrates Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor IX VHP (Bio-transfusion), Alphanine (Alpha) and Mononine (Armour) have been studied in vitro and compared with the prothrombin complex concentrates (PCCs) Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor IX coagulant activity (IX:C) were in good agreement with the manufacturer's label values. In contrast to the PCCs, most of the purified concentrates were virtually devoid of other vitamin K-dependent coagulation factors, the inhibitors protein C and S as well as fibrinogen, fibronectin and immunoglobulins. Indicators of thrombin generation, namely prothrombin fragments 1 and 2 (F 1 + 2) and thrombin-antithrombin complex (TAT), were present in varying amounts in all preparations. The specific activity in the purified concentrates exceeded that in the PCCs by a factor of 50-100. Some differences in purity were found between the purified concentrates. In vivo, Nanotiv was compared with Preconativ and Immunine with Prothromplex TIM4 in crossover studies in patients with severe hemophilia B, and Mononine was tested in a single drug study. Most of the preparations yielded postinfusion increases in TAT, but not in F 1 + 2. Pharmacokinetic variables were analyzed with non-linear curve-fitting combined with model-independent methods. In retrospective comparisons, there were no apparent differences between Nanotiv, Preconativ and Mononine, whereas in vivo recovery seemed lower and the apparent clearance higher for Immunine and Prothromplex. Purified factor IX concentrates were successfully used as cover for surgery or in immune tolerance induction.

Adult↗
PubMed1993

New bleeding time devices with retractable blades evaluated in children, healthy volunteers and patients with prolonged bleeding time.

The Simplate II-R and the Simplate Paediatric, are two new Simplate bleeding time devices with retractable blades. In this study we compared the Simplate II-R with the Simplate II bleeding time and found a good correlation when performed by the same technician both in 30 healthy volunteers and in 7 patients with prolonged bleeding time. The same normal ranges may be applied for the Simplate II-R as for the Simplate II bleeding time. The Simplate II-R bleeding time was highly reproducible in healthy volunteers when performed by the same technician. We found no correlation between age and bleeding time, and no significant difference in bleeding time between males and females. We performed the Simplate Paediatric bleeding time test and calculated the normal ranges in 84 healthy children in 4 age groups: 3 days, 3 months, 1 year and 3-6 years of age. The Simplate Paediatric bleeding times were shorter in the children than the Simplate II-R bleeding times in the adults. We found no significant correlation between bleeding time and the inverse platelet count, and no significant difference in bleeding time between boys and girls. The retractable blades in the Simplate II-R and the Simplate Paediatric reduce the risk of accidental cuts. Both devices yield reproducible bleeding time measurements and can be used instead of older Simplate variants.

Adult↗