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Biomedical subjects

E Berntorp

Publications and source records attributed to E Berntorp.

At least 127 records · Page 7Linked to original sources
PubMed1994

Psychosocial self-prognosis in relation to mortality and morbidity in hemophiliacs with HIV infection.

HIV-infected hemophiliacs participated in a psychosocial prognosis study. The Coping Wheel was filled out 1-2 years after the subjects had been told that they were HIV-infected and between 1 and 7 years after they had become infected. The number of significant signs of disease as well as mortality were recorded during the years following the psychosocial measurements. These measures were related to three measures of anticipated future activities derived from the Coping Wheel, namely 'number of activities for oneself', 'number of activities with others' and a combined measure 'number of activities for oneself in relation to number of activities with others'. The results indicated that the subject's own psychosocial prognosis added to the prediction of mortality. The most important psychosocial factor was the combined measure: those with few anticipated activities for oneself in relation to activities with others had a greater likelihood of dying soon during follow-up. The latter prediction was true even after adjustment for age and condition of the immune system (CD4 count) at the start of follow-up. The conclusion is that the Coping Wheel, applied as in the present examination, may be of help in prognosis and in identifying psychosocial needs in patients with HIV infection.

Adaptation, Psychological↗
PubMed1994

Low-dose aspirin to pregnant women: single dose pharmacokinetics and influence of short term treatment on bleeding time.

Single dose pharmacokinetics of 75 mg aspirin was investigated in two groups of ten women with clinically normal pregnancies. Eleven non-pregnant subjects in the same age were controls. In group A, gestational age was 27-30 completed weeks, and in group B, 36-39 weeks. Venous blood samples were taken before and up to 240 minutes after the intake of the aspirin. Liquid chromatographic assays for acetylsalicylic acid (ASA) and its metabolite, salicylic acid (SA), was performed. The pharmacokinetics of ASA and SA were similar in group A and B but pregnant subjects had a slower uptake and a lower peak level than controls. The late elimination phase for their compound did not differ between the groups. Nine pregnant women with normal pregnancies had their bleeding time measured by a modified Ivy technique using a Simplate II device before, at the end of, and two weeks after daily administration of 75 mg ASA for two weeks. All had a normal bleeding time before and two weeks after the end of the medication. Eight of the nine subjects had an increased bleeding time by Ivy tests, (p < 0.01) whereas the bleeding time assessed by Duke's method was within normal limits. These studies suggest that during pregnancy changes of the uptake rate and distribution volume modulate the pharmacokinetics of ASA and that this drug given in low dosage to gravidae marginally alters their platelet function.

Aspirin↗
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

Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate.

The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC-ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ.

Adolescent↗
PubMed1993

Low-dose warfarin decreases coagulability without affecting prothrombin complex activity.

OBJECTIVES: To assess the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII:C) and to investigate the effects on the plasma coagulation cascade. DESIGN: An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day-1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day-1. Prothrombin fragment 1 + 2 (F(1 + 2)), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1 + 2) was used as a marker of thrombin formation. SUBJECTS: Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. RESULTS: Warfarin 1.25 mg day-1 lowered FVII:C from 113 U dl-1 to 107 U dl-1 (P = 0.025) and F(1 + 2) from 1.60 nmol l-1 to 1.27 nmol l-1 (P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day-1 induced further lowering of FVII:C (91 U dl-1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. CONCLUSION: Warfarin 1.25 mg day-1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.

Adult↗
PubMed1993

Pharmacokinetic dosing in prophylactic treatment of hemophilia A.

The aim of this study was to investigate individual pharmacokinetics as a tool for dosing of factor VIII (FVIII) in severe hemophilia A. It is assumed that effective prophylaxis against bleedings is maintained if the plasma FVIII:C activity is kept above 1 U/dl, and the present study is based on this assumption. A current standard dosage regimen for FVIII is 25-40 U/kg up to three times weekly. However, there is considerable individual variation in the pharmacokinetics of FVIII:C. Individual pharmacokinetic data were used to computer-simulate plasma activity curves after repeated doses in 8 patients. Going from prophylaxis regimens of normally 2-3 infusions per week to dosing every 2 days would theoretically reduce their average FVIII consumption by 43% with maintained or increased trough levels of FVIII:C. Daily dosing would reduce their mean FVIII usage by 82%. Modified dosage regimens, infusions every 2 days, were implemented in the patients, and plasma samples were drawn to verify the pharmacokinetic models. The feasibility of the method to generally raise trough levels with a decreased consumption of FVIII was confirmed. Dosing of coagulation factors according to kinetic principles can result in more cost-effective utilization of these very expensive preparations.

Adult↗
PubMed1993

Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor.

Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu.

Adolescent↗
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

Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B.

In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.

Adolescent↗
PubMed1992

Implantable central venous catheter facilitates prophylactic treatment in children with haemophilia.

Twelve children with a severe form of haemophilia A received a totally implantable venous access system (Port-A-Cath) to facilitate regular prophylactic treatment with factor VIII. The indication for implantation was difficulty in obtaining regular access to a peripheral vein. Postoperative bleeding around the portal site occurred in two of 12 cases. After a median duration of follow-up of 26 months (range 5-79 months), none of the systems had needed replacement due to bleeding, septicaemia or thrombosis. One child, with an inhibitor against factor VIII, had an infection at the portal site and this system was removed. None of the other children had any serious side effects. Nine of the 12 children's parents learned how to use the Port-A-Cath system, thus enabling optimal prophylactic home treatment with factor VIII to be begun early in life.

Catheterization, Central Venous↗
PubMed1992

Pharmacokinetics of factor VIII in humans. Obtaining clinically relevant data from comparative studies.

The pharmacokinetics of Factor VIII procoagulant activity (FVIII:C) were investigated in 10 patients receiving 2 different high purity concentrates of FVIII. The in vivo recovery of FVIII:C depended on the method of blood volume estimation and on the in vitro assay used to define the potency of the concentrate; more generally, it also depends on the study design. The use of in vivo recovery to compare FVIII preparations should therefore be discouraged and the achieved area under the FVIII activity-time curve (AUC) should be used instead. The volume of distribution at steady-state (Vss) of FVIII:C was significantly greater than the estimated plasma volume of the patients. The mean terminal half-life of FVIII:C was slightly assay-dependent, being 14h by a 1-stage clotting assay and 12h by a chromogenic assay. The calculated apparent clearance (CL) of FVIII:C, as well as the Vss and the in vivo recovery, depended on the measured in vitro potency of the FVIII concentrate. These methodological aspects of pharmacokinetic studies are of direct interest to the clinician, since the routine administration of FVIII is based on the pharmacokinetic properties of the specific preparation.

Chromatography, Affinity↗
PubMed1992

Autologous blood transfusion in revision hip arthroplasty. A prospective, controlled study of 30 patients.

In a prospective, randomized study of the efficacy and effects of autologous blood transfusion in revision hip arthroplasty, 30 patients were randomly allocated into two groups. The Control Group received homologous blood transfusion. The Study Group deposited 2-3 units of blood preoperatively, intraoperative blood salvage was used, and no homologous blood was transfused intraoperatively. There was a smaller postoperative blood loss in the Study Group. The preoperative hemoglobin values were lower in the Study Group, but one week postoperatively they were higher than in the Control Group. The decrease in the values of AT III and protein C was lower in the Study Group. The combination of preoperative blood donation and intraoperative blood salvage reduced blood loss and homologous blood transfusion in revision hip arthroplasty.

Aged↗
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

Kinetic aspects of the removal of IgG and inhibitors in hemophiliacs using protein A immunoadsorption.

Seven patients with hemophilia A and B and 3 patients with acquired hemophilia were treated on 13 and 4 occasions, respectively, with protein A immunoadsorption to reduce anti-factor VIII or IX antibodies. Usually the patients were treated on 2 consecutive days. On each treatment day an average of 3 (range: 1.02-5.83) plasma volumes were processed in the congenital patients and 1.5 (range: 1.02-2.90) in those with acquired hemophilia. Plasma levels of IgG decreased from 18.9 +/- 1.9 to 3.1 +/- 1.2 g/l in the congenital group, and from 11.5 +/- 2.3 to 2.3 +/- 0.6 g/l in the acquired group. In the congenital hemophiliacs a corresponding reduction in inhibitor level of 70-95% was regularly seen; in 1 exceptional patient the inhibitor was reduced from 4,350 to 12 Bethesda Units/ml (BU/ml) during 5 days of treatment. In the congenital hemophiliacs immunoadsorption was followed by factor infusion to peak levels between 8 and 215 IU/dl. In the patients with acquired hemophilia a satisfactory reduction in inhibitor levels was obtained in 2 of the 4 treatments, which were followed by DDAVP or factor infusion. Some recommendations for the use of protein A immunoadsorption in the treatment of hemophilic patients will be given.

Adult↗