Search PubMed⌕ Search

Biomedical subjects

E Berntorp

Publications and source records attributed to E Berntorp.

At least 91 records · Page 5Linked to original sources
PubMed1998

Continuous infusion of factor IX concentrate to induce immune tolerance in two patients with haemophilia B.

Two patients with haemophilia B and high-responding inhibitor to factor IX were subjected to immune tolerance induction according to the Malmö protocol, including high dosage of factor IX, cyclophosphamide and intravenous gammaglobulin. In one of the patients the treatment was preceded by extracorporeal protein A adsorption. Both patients had previously been subjected to immune tolerance induction without success and as an attempt to improve the tolerance induction regimen and lower cost, factor IX was given as continuous infusion, with a dose of around 300 units per kg body weight daily for 3 weeks. The inhibitor level declined in one of the patients but tolerance was not achieved. In the second patient the inhibitor level remained high. Despite the failure of the treatment in these two cases, we propose that the constant antigen load provided by the continuous infusion of modern, safe, purified factor IX concentrate may theoretically be of greater benefit in immune tolerance induction than the varying load resulting from intermittent infusions. Larger study materials are needed to show if this is so.

Adolescent↗
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

Multidose pharmacokinetics of factor IX: implications for dosing in prophylaxis.

The aim of this study was to investigate the use of single-dose pharmacokinetic data for factor IX (FIX) to predict multidose pharmacokinetics and explore their use for pharmacokinetic dosing in prophylactic treatment of haemophilia B. Eight patients with severe haemophilia B were enrolled. Using single-dose pharmacokinetic data for each patient, plasma factor IX procoagulant activity (FIX:C) curves during prophylactic dosing were computer-simulated. The simulations were verified by repeated blood sampling and measurements of FIX:C. Theoretical dosing regimens to maintain a plasma trough level of 1.0 U dL-1 of FIX:C were calculated. A 2 x 2 week cross-over study on standard dosing according to bodyweight vs. dosing every three days based on individual pharmacokinetics was carried out. FIX:C was measured during each treatment period. FIX:C data from the plasma sampling generally confirmed the single-dose pharmacokinetic data used. Pharmacokinetically tailored dosing of FIX could result in considerable savings of factor concentrate as compared to current standard dosing. The study demonstrates the applicability of individual pharmacokinetics as a tool for cost-effective utilization of FIX concentrates in the prophylactic treatment of haemophilia B.

Adult↗
PubMed1998

Resource utilisation in haemophiliacs treated in Europe: results from the European Study on Socioeconomic Aspects of Haemophilia Care. The European Socioeconomic Study Group.

The objectives of our study was to answer the following questions: (1) What are the socioeconomic costs and benefits of different haemophilia treatment strategies? (2) Which savings can be achieved through a comprehensive care program? (3) How are haemophiliacs integrated into their social life? (4) What are the annual costs of treating haemophilia from a third party payer perspective? In this cross-sectional study, 840 consecutive haemophiliacs attending 16 haemophiliac treatment centres in 10 European countries at were entered in the study. The following six parameters were analysed: sociodemographic patient data, the type of substitution (on demand or prophylaxis), transfusion-transmitted diseases, the functional joint status, quality of life as well as the total costs of therapy. Three kinds of substitution modalities were distinguished: on demand therapy, pure and modified prophylaxis. The average number of medical visits, the average length of hospital stay, regular drug therapy and the average number of days off work per bleeding joint were recorded from the medical charts as a basis for the subsequent assessment of the costs of therapy. The total study sample comprised of 566 patients. Interestingly, statistically more significant (P = 0.0005) patients were unemployed in the on-demand group (14%) than in the prophylaxis group (3.4%). There was a higher ratio of white collar workers in the on-demand group as compared to the prophylaxis group and vice versa for blue collar workers. The distribution of blue collar workers, clerk, self-employed persons, students and housemen were quite comparable between the patients of the on-demand and prophylactic therapeutic regimen. The labor force participation rate was 55.2% in the patients in the on demand and 59.3% in the patients in the modified prophylactic group. The labor force participation rate across all patients was 56%. Patients on demand therapy used on average 38.3 (median: 12.5) units/kg/week as compared to 68.6 (median: 6) units/kg/week in the prophylaxis group. The mean usage across all patients was 46.1 (median 19.7) units/kg/week. There were an average of 7.4 (median: 3) joint bleeds per patient across all patients during the 6-month observation period. In the on-demand group 8.8 (median: 5) joint bleeds were recorded versus 3.1 joint bleeds (median: 0) in the prophylactic group. This difference was statistically different (95% CI of difference: 4.33-7.07). Our data suggest that patients receiving prophylactic clotting factor therapy require less additional health care resources, mainly due to the reduction in the number of joint bleeds.

Adolescent↗
PubMed1998

Liposuction in Dercum's disease: impact on haemostatic factors associated with cardiovascular disease and insulin sensitivity.

OBJECTIVE: To study the impact of adipose tissue removal by liposuction on factors associated with increased risk of cardiovascular atherosclerotic disease within the coagulation and fibrinolytic system and glucose metabolism. DESIGN, SETTING AND SUBJECTS: Liposuction was performed in 53 patients with Dercum's disease. The levels of fibrinogen, von Willebrand factor antigen (VWF:Ag) and plasminogen activator inhibitor type 1 activity (PAI-1) were measured preoperatively, and 2 weeks, 4 weeks and 3 months postoperatively. In a subsample of 10 patients, insulin sensitivity was determined before and 2-4 weeks after surgery using the 2-h euglycaemic hyperinsulinaemic clamp technique. The study was performed as a single-centre study. MAIN OUTCOME MEASURE: Fibrinogen, PAI-1 and VWF:Ag levels, and glucose uptake before and after removal of adipose tissue. RESULTS: Weight reduction was sustained throughout the follow-up period with a mean decrease from 90.7 to 86.6 kg (P < 0.0001). There was a slight increase in levels of coagulation factors 2 and 4 weeks postoperatively, probably in reaction to the surgical trauma. After 3 months the values had returned to preoperative levels except for PAI-1, which still showed a slight increase (P < 0.05). In the subsample of 10 patients, glucose uptake was improved (P < 0.05) from a short-term perspective after surgery. CONCLUSION: Surgical removal of adipose tissue, without change in lifestyle, does not seem to improve the levels of coagulation and fibrinolytic factors associated with cardiovascular atherosclerotic disease, whereas glucose takeup may be facilitated and insulin sensitivity increases from a short-term perspective.

Adiposis Dolorosa↗
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

Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation.

Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths. The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage. Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

Adolescent↗
PubMed1998

Failure of thrombolytic therapy in patients with myocardial infarction is associated with high plasma levels of factor VII antigen.

Thrombolytic therapy in acute myocardial infarction fails to re-establish coronary blood flow in a significant number of patients. One reason for this may be haemostatic imbalance. We investigated whether coagulation factor VII antigen (FVIIag), fibrinogen and protein C were related to reperfusion. Plasma from 45 patients was drawn before treatment and reperfusion assessed by means of continuous, on-line, vector-ECG analysis. Among the 17 patients with no reperfusion, FVIIag levels were significantly higher than among the 28 with signs of reperfusion (560 vs. 410 microg/l median, p = 0.006). Protein C levels where higher in the group with successful reperfusion (1.10 vs. 1.01 U/ml median, p = 0.03), whereas no difference was seen in fibrinogen levels. The findings were not influenced by plasma-triglycerides, body-mass index, age or time between onset of chest pain and thrombolytic therapy. The results suggest that FVII is of importance for the formation as well as resolution of coronary clots.

Adult↗
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

No effect of a new second-generation B-domain-deleted recombinant product on lymphocyte transformation in vitro: a study of plasma-derived and recombinant products.

Immunomodulatory effects of various factor VIII and factor IX clotting factor concentrates (CFCs) and of albumin were evaluated by a sensitive assay measuring the incorporation of 3H-thymidine in phytohaemagglutinin-stimulated lymphocytes in the presence of monodansylthiacadaverine. In contrast to previous findings by others, we found lymphocyte transformation to be inhibited by all plasma-derived factor VIII concentrates at concentrations of 0.02, 0.2 and 2.0 IU/ml, including those purified by monoclonal antibodies (P < 0.05). Kryobulin TIM3 had the most pronounced effect. In addition, three plasma-derived human albumin preparations exerted a similar inhibitory effect as the factor VIII concentrates, whereas the corresponding plasma-derived factor IX concentrates only manifested minor immunomodulatory effects. Of the recombinant preparations, only Recombinate exerted an inhibitory effect at 0.02 and 0.2 IU/ml, whereas both Kogenate and Recombinate decreased 3H-thymidine incorporation at 2.0 IU/ml (P = 0.01). No immunomodulatory effect at all was observed with r-VIII SQ, a new B-domain-deleted recombinant factor VIII preparation free from added albumin. The significance of this finding regarding immunological side-effects including inhibitor development remains to be evaluated, but this second-generation recombinant product opens up new and interesting perspectives yet to be explored.

Cadaverine↗
PubMed1997

Haemophilia prophylaxis in young patients--a long-term follow-up.

OBJECTIVES: To review long-term prophylactic factor treatment in young patients with severe haemophilia A and B, focusing on the orthopaedic and radiological outcome. DESIGN: We received 34 patients with severe haemophilia A (n = 29) and B (n = 5), aged 7-22 years. Age at start of treatment was 1-4.5 years. Dosages of factor concentrate (F VIII and F IX, respectively) were 25-40 IU/kg body weight, three times a week for haemophilia A and twice a week for haemophilia B. The patients had been checked annually over a 5-year period (1990-95). Orthopaedic and radiological joint scores were evaluated according to recommendations by the World Federation of Haemophilia. SETTING: All results were obtained at the Department for Coagulation Disorders, University of Lund, Malmö University Hospital, Malmö, Sweden. RESULTS: Orthopaedic and radiological joint scores were found to have remained unchanged during follow-up in almost all patients and to be still zero (i.e. no unaffected joints) in 79% (n = 27) of the patients. CONCLUSION: There is a growing international consensus haemophilic arthropathy can be prevented by administering early high-dose prophylaxis. The results of the present investigation strongly support this opinion.

Adolescent↗
PubMed1997

Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.

This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.

Adult↗
PubMed1997

Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis.

Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution or arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found fewer than 10-15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20-60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1-15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.

DNA Mutational Analysis↗
PubMed1997

Haemostatic variables in Pacific Islanders apparently free from stroke and ischaemic heart disease--the Kitava Study.

We cross-sectionally measured plasminogen activator inhibitor-1 (PAI-1) activity, fibrinogen, factor VII (FVII:C) and VIII (FVIII:C) coagulant activity, and von Willebrand factor antigen (VWF:Ag) in 162 traditional horticulturalists older than 40 years from the tropical island of Kitava, Papua New Guinea, where the intake of western food is negligible and where stroke and ischaemic heart disease appear to be absent. Identical analyses were made in Swedish subjects of comparable ages. Kitavams had markedly lower PAI-1 activity, with 85% of males and 100% of females having PAI-1 activity < or = 5 U/ml, as compared with 22 and 14% in Swedish males and females (p < 0.0001). Surprisingly, Kitavans also had higher FVII:C. FVIII:C and VWF:Ag. Fibrinogen was 10% lower in Kitavan males while 25% higher in Kitavan females. The very low PAI-1 activity in Kitavans may explain some of their apparent freedom from cardiovascular disease and probably relates to their extreme leanness.

Adult↗
PubMed1997

Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients.

The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.

Adolescent↗
PubMed1997

Second generation, B-domain deleted recombinant factor VIII.

A second generation recombinant factor VIII product has been developed and has been undergoing clinical trials since 1993. It is named r-VIII SQ and differs from other recombinant and plasma-derived products in that the B-domain of the molecule, to which no function has yet been ascribed has been deleted. It also has a formulation which does not include albumin. The specific activity is extremely high, 15,000 IU VIII:C/mg protein, and the stability of the reconstituted product is highly satisfactory. The pharmacokinetic properties are similar to those of a monoclonal purified, plasma-derived factor VIII. In clinical trials experience has been acquired from more than 87 previously treated patients on long-term treatment, 20 patients subjected to surgery and 72 previously untreated patients. The record with regard to efficacy and safety is excellent but more experience is needed, especially regarding the risk of inhibitor development. The B-domain-deleted recombinant factor VIII has the potential to improve convenience and cost-benefit in haemophilia care. The safety margin regarding human viruses and other protein contaminants should be better with r-VIII SQ than with earlier products, which all contain far more human protein in their formulations.

Animals↗