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Biomedical subjects

E Berntorp

Publications and source records attributed to E Berntorp.

At least 109 records · Page 6Linked to original sources
PubMed1996

Increased fetal loss in women with heritable thrombophilia.

BACKGROUND: A successful outcome of pregnancy requires an efficient uteroplacental vascular system. Since this system may be compromised by disorders of haemostasis associated with a prothrombotic state, we postulated that maternal thrombophilia might be a risk factor for fetal loss. We studied the relation between heritable thrombophilic defects and fetal loss in a cohort of women with factor V Leiden or deficiency of antithrombin, protein C, or protein S. METHODS: We studied 1384 women enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). Of 843 women with thrombophilia 571 had 1524 pregnancies; of 541 control women 395 had 1019 pregnancies. The controls were partners of male members of the EPCOT cohort or acquaintances of cases. We analysed the frequencies of miscarriage (fetal loss at or before 28 weeks of gestation) and stillbirth (fetal loss after 28 weeks of gestation) jointly and separately. FINDINGS: The risk of fetal loss was increased in women with thrombophilia (168/571 vs 93/395; odds ratio 1.35 [95% Cl 1.01-1.82]). The odds ratio was higher for stillbirth than for miscarriage (3.6 [1.4-9.4] vs 1.27 [0.94-1.71]). The highest odds ratio for stillbirth was in women with combined defects (14.3 [2.4-86.0]) compared with 5.2 (1.5-18.1) in antithrombin deficiency, 2.3 (0.6-8.3) in protein-C deficiency, 3.3 (1.0-11.3) in protein-S deficiency, and 2.0 (0.5-7.7) with factor V Leiden. The corresponding odds ratios for miscarriage in these subgroups were 0.8 (0.2-3.6), 1.7 (1.0-2.8), 1.4 (0.9-2.2), 1.2 (0.7-1.9), and 0.9 (0.5-1.5). Significantly more pregnancy terminations had been done in women with thrombophilia than in controls (odds ratio 2.9 [1.8-4.8]); this discrepancy was apparent in nine of 11 participating centres and for all thrombophilia subgroups. INTERPRETATION: Women with familial thrombophilia, especially those with combined defects or antithrombin deficiency, have an increased risk of fetal loss, particularly stillbirth. Our findings have important implications for therapy and provide a rationale for clinical trials of thromboprophylaxis for affected women with recurrent fetal loss.

Abortion, Spontaneous↗
PubMed1996

The treatment of haemophilia, including prophylaxis, constant infusion and DDAVP.

Recent years have witnessed advances in the treatment of haemophilia such as the introduction of prophylaxis, continuous infusion and pharmacological treatment with desmopressin (DDAVP). Prophylactic treatment on a long-term basis appears to be effective in preventing the development of arthropathy in severe haemophilia. The largest body of experience is that from Sweden, where prophylaxis is started at the age of 1-2 years. The dosage used is 25-40 U factor VIII/IX per kilogram bodyweight given three times or twice weekly, respectively. In some cases an intravenous access device has to be used during the first years of treatment. The patients grow up like normal boys and can live virtually normal lives. The beneficial psychological impact of prophylaxis on the family cannot be overestimated. Side-effects are not more frequent with prophylaxis than with on-demand treatment. The feasibility of continuous infusion of factor VIII/IX concentrates during bleeding episodes, or as cover for surgery, has been documented. This mode of delivery increases convenience and the cost-benefit ratio of the treatment, with savings in postoperative replacement of factor concentrate of about 50-75%. Many modern concentrates are stable enough for the purpose, and several pump systems, including portable ones, are available. The haemostatic drug DDAVP can be effectively used in most cases of mild haemophilia A. Intravenous administration is to be preferred as cover for surgery or in the case of severe bleeds. There is an effective nasal spray which can also be used for home therapy in mild or moderate bleedings.

Adolescent↗
PubMed1996

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries.

OBJECTIVE: Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q506). To test the importance of the FV:Q506 mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years. DESIGN, SETTING AND SUBJECTS: In a retrospective case-control study, the FV:Q506 mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex- and age-matched controls. MAIN OUTCOME MEASURE: The prevalence of FV:Q506 mutation. RESULTS: The FV:Q506 mutation was found in 18% of patients versus 11% of controls (P = 0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P = 0.03), the calculated odds ratio being 2.6 (95% CI, 1.1-6.4). CONCLUSION: The high prevalence of the FV:Q506 mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC-resistant patients. The prevalence of the FV:Q506 mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.

Adult↗
PubMed1996

Coagulation and fibrinolytic factors in normotensive hypertension-prone men.

OBJECTIVE: To evaluate whether a family history of hypertension is associated with disturbances in the coagulation and fibrinolytic systems. SUBJECTS: Thirty-five normotensive men with a family history of hypertension (relatives) and 27 age- and body mass index-matched controls with a family history (controls). METHODS: Insulin sensitivity was determined with a euglycaemic hyperinsulinaemic clamp technique. Maximal oxygen uptake was estimated from a submaximal work test. Blood samples were analysed for several coagulation and fibrinolytic factors. RESULTS: Relatives had higher plasma levels of plasminogen activator inhibitor-1. Levels of plasma factor VII, prothrombin fragments 1 and 2, fibrinogen and von Willebrand factor antigen did not differ significantly between the groups. However, antithrombin III, protein C and protein S levels were higher in the relatives than in the controls. Coagulation and fibrinolytic factors correlated to waist circumference, insulin sensitivity, maximal oxygen uptake and serum triglycerides level. CONCLUSIONS: Normotensive men with a family history of hypertension have an inhibited fibrinolysis, but also higher levels of several anticoagulant factors. The clinical application of these findings for the future development of cardiovascular disease warrants additional studies.

Adult↗
PubMed1996

Why prescribe highly purified factor VIII and IX concentrates?

The aftermath of the HIV catastrophe and hepatitis virus transmission to hemophiliacs has been characterized by continuous efforts to improve the purity of factor VIII and factor IX concentrates, increasing sophistication of the virucidal methods used, and the introduction of recombinant factor VIII. The cost of hemophilia care is substantial and there is a large price difference between products depending on their purity; generally, the purer the concentrate, the higher the price. The use of expensive highly purified concentrates may be questioned if these products are not superior in terms of safety, efficacy or convenience. The properties of concentrates used in hemophilia care are discussed in this review, as are their safety and side effects. The available data do not clearly reveal any clinical difference between factor VIII concentrates, although the highly purified products may be of theoretical benefit. With regard to factor IX, purified products do not seem to carry any risk of the well-known thromboembolic complications which occur in certain situations after treatment with prothrombin complex concentrates.

Drug Contamination↗
PubMed1995

Primary antiphospholipid syndrome associated with postoperative primary adrenal failure.

A 51-year-old Caucasian male without previous history of thromboembolic disease developed Coomb's positive haemolytic anaemia, thrombocytopenia, transient paranoid psychosis and bilateral adrenal haemorrhage with primary adrenal failure after surgery for inguinal hernia. The activated partial thromboplastin time was spontaneously prolonged, and lupus anticoagulant and anticardiolipin antibodies were detected. In the absence of criteria for classification of systemic lupus erythematosus (SLE), the entity was classified as a primary antiphospholipid syndrome. Despite the persistence of the serological abnormalities, the patient remains well after substitution with cortisone. Primary adrenal failure due to adrenal haemorrhage can be associated with the primary antiphospholipid syndrome.

Adrenal Gland Diseases↗
PubMed1995

Properties of factor IX concentrates.

Five purified concentrates--Nanotiv (Kabi Pharmacia), Immunine (Immuno), Factor IX VHP (Biotransfusion), Alphanine (Alpha Therapeutic Corporation), and Mononine (Armour Pharmaceutical Company)--were characterized biochemically and their in vivo pharmacokinetic and thrombogenic properties evaluated. The results were compared with those for two prothrombin complex concentrates (PCCs): Preconativ (Kabi Pharmacia) and Prothromplex TIM4 (Immuno). The measured values for factor IX coagulant activity (FIX:C) generally agreed with the manufacturers' labeled values. The purified concentrates were virtually devoid of other vitamin K-dependent coagulation factors, the inhibitor proteins C and S, and either fibrinogen, fibronectin, or immunoglobulins. Indicators of thrombin generation (i.e., prothrombin fragments F1 + 2 and thrombin-antithrombin complex) were present in varying amounts in all preparations. The level of specific activity in the purified concentrates exceeded that in the PCCs by a factor of 50- to 100-fold. Pharmacokinetic variables were studied in severe hemophilia B patients: Nanotiv was compared with Preconativ; Immunine was compared with Prothromplex TIM4 in crossover studies; and Mononine was tested in a single-drug study. No differences were apparent between Nanotiv, Preconativ, and Mononine, but recovery rates were lower, clearance rates higher, and FIX:C half-life shorter for Immunine and Prothromplex TIM4, although the disparate results might have been attributable to methodologic differences. Purified factor IX concentrates were used successfully as cover for surgery and in immune tolerance induction without observable adverse effects.

Antithrombin III↗
PubMed1995

Modern treatment of haemophilia.

Many rapid advances have been made in the diagnosis and therapy of haemophilia. Nevertheless, the condition still poses problems and challenges (e.g., joint disease, transfusion-transmitted diseases, inhibitors, provision of care in developing countries, and education and cost issues). WHO and the World Federation of Hemophilia held a joint meeting in Geneva, on 21-23 March 1994, to discuss and review current and future approaches to the management of haemophilia and its complications, including prospects for genetic technology and gene therapy in developed and developing countries. The present review article summarizes the discussions and recommendations made by the participants.

Consumer Product Safety↗
PubMed1994

Pharmacokinetics of factor IX in patients with haemophilia B. Methodological aspects and physiological interpretation.

The aims of this study were to investigate the influence of total blood sampling time on the estimated pharmacokinetic parameters of Factor IX procoagulant activity (FIX:C) and to relate the pharmacokinetics of FIX:C to the putative physiological disposition of Factor IX (FIX). Six patients with severe haemophilia B each received 2 infusions of FIX and on both occasions blood samples were collected for 104 h. Each FIX:C decay curve was processed with successive deletion of the last (remaining) datapoint. The fitted terminal half-life (t1/2 beta) and the calculated model-independent mean residence time (MRTMI), elimination clearance (CLMI) and volume of distribution at steady state (Vss) stabilised close to their final values when FIX:C data corresponding to at least 56 h of sampling were used. The final mean values were t1/2 beta = 34 h, MRTMI = 37 h, CLMI = 4.0 ml.h-1.kg-1 and Vss = 0.15 l.kg-1. The disposition of FIX could be characterised by a two-compartment pharmacokinetic model. On average, FIX molecules spent 44% of their total MRT in the second (or "extravascular") compartment. The distribution clearance was comparable to estimated total lymph flow. The volume of the central compartment was twice the estimated plasma volume, which may reflect the rapid and reversible binding of FIX to vascular endothelium. This explains the common clinical finding that the peak activity of FIX:C is less than the injected dose divided by the estimated plasma volume of the patient.

Blood Specimen Collection↗
PubMed1994

A NlaIII polymorphism within the human factor VII gene.

The polymorphism is located within exon 5 of the human coagulation factor VII gene and is silent at the amino acid level. The distribution pattern is similar in Caucasians and African Americans. This polymorphism may be useful for restriction fragment length polymorphism (RFLP) diagnosis of factor X deficiency as well as factor VII deficiency, since the factor X gene is closely linked to the factor VII locus.

Base Sequence↗
PubMed1994

Coping style in relation to the consumption of factor concentrate in HIV-infected hemophiliacs during the years after their infection became known.

A psychosocial investigation offered to all HIV-infected men with moderately severe or severe hemophilia in Sweden was made in 1986. Most of these men had been infected in the years 1980-1984 and told about their own infection in 1985. A noninfected group of hemophiliacs was used as a reference group in the psychosocial investigation. A psychosocial prognosis was made on the basis of the coping style observed by means of the Coping Wheel. Among subjects who showed evidence of a passive-pessimistic copying style, there was a significant decrease in the number of factor concentrate units received in 1987 and 1988. Among subjects in the group with a more active-optimistic coping style, there was a tendency of increasing the use of factor concentrate during the years after the HIV-infection became known. This result indicates that awareness of HIV-infection may influence specific hemophilia behavior among subjects with passive-depressed copying style.

Adaptation, Psychological↗