Breastfeeding does not influence the development of inhibitors in haemophilia.

Our aim was to test the hypothesis that breastfeeding may reduce development of inhibitors in male infants with haemophilia by inducing an oral immune tolerance to factor VIII. To achieve that goal, we performed a structured epidemiological survey comprising all males born with severe haemophilia A (in all 100 patients, 19 with inhibitors) or haemophilia B (in all 16 patients, six with inhibitors) in Sweden in 1980-99. Our results show no protective effect of breastfeeding

Costs of on-demand and prophylactic treatment for severe haemophilia in Norway and Sweden.

The expected annual cost (in the year 2000 prices) for a 30-year-old patient with average individual and treatment characteristics for on-demand EUR 51 832 (95% CI: 44 324-59 341) and for prophylaxis EUR 146 118 (95% CI: 129 965-162 271), was obtained from panel-data analysis of an 11-year retrospective panel of 156 patients with severe haemophilia in Norway and Sweden. Costs included haemophilia-related treatment costs within the health-care sector (factor concentrate, doctors' visits, diagnostic procedures, hospitalisation, invasive procedures, etc.) and cost for haemophilia-related resource use in other sectors (lost production, use of special equipment, adaptation of workplace and domicile, etc). Although costs of lost production, reconstructive surgery and hospitalisation were higher for on-demand, they did not balance out the higher costs of factor-concentrate consumption in prophylaxis. The cut-off risk of premature death, where on-demand and prophylaxis would have been equally costly, was 3.7 percentage units higher for on-demand than for prophylaxis. Such a great risk difference has not been reported elsewhere to our knowledge. Estimated cost-elasticities indicated that annual costs of prophylaxis would increase by approximately the same proportion as a potential increase in the price of factor concentrate and decrease less than proportionately with a reduction in prescribed dose kg-1. For on-demand, the annual costs would increase by approximately the same proportion as an increase in the prescribed dose kg-1

On-demand vs. prophylactic treatment for severe haemophilia in Norway and Sweden: differences in treatment characteristics and outcome.

Using an 11-year panel of 156 Norwegian and Swedish patients with severe haemophilia, and including retrospective case-book data from birth, we compared the differences in the haemophilia-related resource use between on-demand and prophylactic treatment. Patients treated on-demand had more surgery (arthrodeses, prostheses implantations and synovectomies) and more days lost from work. Median annual factor-concentrate consumption among adults (18+) was 211 000 IU [interquartile range (IQR) 154 000-268 000] or 3 024 IU kg-1 year-1 for patients on prophylactic treatment and 55 000 IU (IQR 28 000-91 000) for on-demand patients (780 IU kg-1 year-1). This was partly explained by the fact that the median dose per kg body weight was twice as great 28, (IQR 24-32) for prophylaxis compared with 14 (IQR 12-16) for on-demand. Prescribed dose per kg body weight was found to be an important factor explaining the variation in total annual factor-concentrate consumption per patient for both types of treatment. Other variables included in the panel-data regression analysis were the number of weeks on secondary prophylaxis for on-demand patients and age, body weight and type of haemophilia for children (0-17 years) on prophylaxis. Differences were consistently substantial and will affect both costs and benefits of the two treatment strategies

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 Malmo 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

Tranexamic acid - an old drug still going strong and making a revival.

Experience with tranexamic acid, an indirect fibrinolytic inhibitor, started as soon as it was released from Shosuke Okamoto's lab in the early 1960s. It was first prescribed to females with heavy menstrual blood loss and to patients with hereditary bleeding disorders. Soon the indications were widened to elective surgery because of its blood saving effects. Contraindications are few, most important is ongoing venous or arterial thrombosis and allergy to tranexamic acid, and the doses has to be reduced in renal insufficiency. In randomized controlled trials, however, patients with other risk factors are excluded as well (patients with history of cardiovascular disease, thromboembolism, bleeding diathesis, renal failure with creatinine >250μmol/L, pregnancy, and patients on treatment with anticoagulants). Recent meta-analyses of several randomized controlled trials in orthopedic arthroplasty have shown that tranexamic acid reduces peri- and postoperative blood loss, blood transfusion requirements and reoperations caused by bleedings. In general, the preoperative dose was 10-15mg/kg i.v. (or 1g), followed or not, by one or two doses, some as continuous infusion i.v. To validate relationship between dose and effect more data are needed. No evidence was found of increased thromboembolic accidents or other adverse events in the patients on tranexamic acid compared to the control groups. In major cardiac surgery tranexamic acid has been used in a large number of controlled trials with various dosing schemes in which the highest dosages seem to be associated with neurotoxicity; therefore a maximum total dose of 100mg/kg especially in patients over 50years of age is recommended by ISMICS (International Society for Minimally Invasive Cardiothoracic Surgery). Other indications for tranexamic acid are reviewed here as well. In recent years the extensive trial in severe trauma with massive bleedings using tranexamic acid was presented, CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) comprising more than 20,000 patients. It showed that the survival was increased when tranexamic acid was given early after the accident compared to placebo; further studies are taking place is this field to get more information. Of utmost importance is the ongoing WOMAN (World Maternal Antifibrinolytic) a randomized, double-blind, placebo controlled trial among 15,000 with clinical diagnosis of postpartum haemorrhage bearing in mind that each year a large number of women in low and middle income countries, die from causes related to childbirth. In summary, we consider tranexamic acid is a drug of great value to reduce almost any kind of bleeding, it is cheap and convenient to use and has principally few contraindications. It may be added, that tranexamic acid is included in the WHOs list of essential medicines

Lack of very strong association between pre-treatment fibrinogen and PAI-1 with long-term mortality after coronary bypass surgery

Aim: To explore the association between the coagulation protein fibrinogen and the fibrinolytic biomarker plasminogen activator inhibitor-1 ( PAI- 1) and the long- term mortality after coronary artery bypass grafting ( CABG). Patients and Methods: In 729 patients undergoing CABG at Sahlgrenska University Hospital, a blood sample for fibrinogen and PAI-1 was collected prior to the procedure. Patients were followed for 10 years. Results: Among patients with high levels of fibrinogen (> 3.6 g/ l; median), the 10-year mortality was 32.3 vs. 20.7% among patients with fibrinogen levels below the median ( p = 0.0005). However, patients with higher levels of fibrinogen were older and had an adverse risk factor pattern. When adjusting for these differences, pre- operative fibrinogen levels did not clearly appear as an independent predictor of long- term mortality. The 10- year mortality was similar in patients with high ( 25.3%) and low ( 26.5%) levels of PAI-1. Conclusion: Our results do not suggest that fibrinogen and PAI- 1, when evaluated prior to the operative procedure, arestrongly associated with increased mortality in the longterm after CABG, when other co-morbidity factors are simultaneously considered