An East Danish population of acquired haemophilia A (factor VIII inhibitors) patients are described in a retrospective survey. Fifteen patients attended the centre during the period 1981-1994. The epidemiology, clinical presentation, time from début until diagnosis and response to treatment are presented. Acquired factor VIII inhibitors are rare and without treatment the disease has a high mortality and morbidity. Inhibitors mostly develop among the elderly, independent of sex and almost half have no known underlying disease. When the diagnosis is clear, bleedings may be controlled and the patient may be cured by treatment that eliminates the inhibitor. Time until diagnosis varies a lot, for some patients it takes years. It is therefore important to be aware of the disease, so that time with risk of fatal bleeding is shortened as much as possible.
Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C: results of a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment.
Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and treatment discontinuation were based upon changes in transaminase levels. Forty-seven patients enrolled received 3 MU of alpha interferon thrice weekly (TIW) for 3 months. Twenty-six nonresponders had their dose increased to 6 MU TIW for an additional 3 months, while 21 responding patients continued on 3 MU TIW. At 6 months, 25 patients with a complete or a partial biochemical response were randomly allocated to either a fixed dose regimen (13 patients) (3 or 6 MU thrice weekly) or an individualized dose regimen (12 patients) tapering interferon dose from 3 or 6 MU by one-third every 2 months if transaminases were persistently normal. The remaining 22 biochemical nonresponders were followed for an additional 6 months without further treatment. After 12 months of treatment, 18 patients (38%) had a virological response, irrespective of regimen, and seven patients (16%) had a sustained virological and biochemical response after 6 months of follow up. Overall, the individualized treatment regimen did not seem to offer any advantage over the fixed dose regimen. The response to alpha interferon treatment in Danish haemophiliac patients with chronic hepatitis C immediately after treatment is comparable to that obtained in previous studies among nonhaemophiliacs. However, a sustained virological and biochemical response was seen in only 16% of treatment patients.
Screening of 43 healthy Danish haemophiliacs revealed a significantly lower helper/suppressor (H/S) ratio than in controls. 8 of the haemophiliacs had an H/S ratio less than or equal to 1.0. A significant negative correlation occurred between the total lifetime factor VIII treatment and the H/S ratio. However, high-dose factor VIII treatment given to patients with antibodies against factor VIII was not associated with immunological abnormalities. Children had a significantly higher H/S ratio than the adult haemophiliacs. Patients exclusively treated with Danish cryoprecipitate during the last year had a significantly higher H/S ratio than patients receiving preparations from other sources. This difference might, however, be explained by lower age and lower total lifetime dose in the group receiving Danish preparations. Haemophiliacs treated with American preparations did not differ immunologically from those treated with preparations of other origin. Total serum IgG was increased in 23% of the patients. This parameter was negatively correlated with the H/S ratio. The possible relation of the observed immunological alterations among otherwise healthy haemophiliacs to the acquired immune deficiency syndrome warrants further attention.
Significant advances have been achieved in prevention of haemophilic disability through prophylactic administration of concentrates and early administration of coagulation factors to control new bleeding episodes, but there is only limited experience with home treatment in haemophilia patients with inhibitors. A home treatment programme using recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) in early intervention against minor bleeds in patients with high responding inhibitors was initiated in Denmark in June 1994. Following careful education and instruction, 2-3 doses each giving 90-100 micrograms/kg bodyweight of rFVIIa were stored in each patient's home. At the onset of a new bleeding episode patients were instructed to inject 1 dose of rFVIIa, and to call the Haemophilia Centre to discuss further management of the episode. If the drug was not completely effective after 1-2 h, a second dose was injected after 3 h. Patients were further instructed to contact us the following day for final efficacy reporting. In total, 7 patients have been enrolled into the study, and to date 114 bleeding episodes have been managed at home with a mean of 2.1 doses per bleed. On 4 occasions, recurrence of bleeding was noted within 24 h. Hospital admission was required in 9 cases, because of a serious injury, insufficient compliance or, in 2 cases, because bleeding required prolonged treatment. Management of these bleeding episodes required a mean of 18 doses. We propose and discuss key criteria for selection of patients for a home treatment programme. The results of this study demonstrate that early intervention in the home setting with rFVIIa is safe and effective in the management of minor bleeding episodes in haemophilia patients with inhibitors.
Prophylaxis is the treatment of choice for children with severe haemophilia. As prophylaxis is especially important during the period of growth, the need for continued prophylaxis in adulthood should be considered. The aim of this study was to describe the incidence and outcome of stopping prophylaxis in patients with severe haemophilia who were offered prophylaxis during childhood. All patients with severe haemophilia (factor VIII/IX
OBJECTIVE--To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN--Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS--86 Men in whom seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE--Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS--Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively). CONCLUSION--The course of primary infection may determine the subsequent course of the infection.
Hemophilia B is caused by a wide range of mutations. In order to characterize the mutations among patients in Denmark, we have systematically screened the entire coding region, the promoter region and exon flanking sequences of the gene encoding factor IX using single strand conformation and heteroduplex analyses. Patients from 32 different families were examined, and point mutations (23 different) were found in all of them. Ten of the mutations have not been reported by others; they include a splice site mutation, a single base pair deletion, and missense mutations. Notably, the study contains a female patient and a previously described Leyden mutation. In ten families with sporadic cases of hemophilia B, all 10 mothers were found to be carriers. The origin of two of these mutations was established.
The AIDS-committee of The Danish Society of Paediatrics has done a nation-wide study among infants and children under the age of 15 with AIDS or HIV-antibodies in preparation for planning prevention and treatment. Clinical data have been collected from the Departments of Paediatrics and Infectious Diseases, Haemophilia, Dermatology and Internal Medicine up to 1 March 1993. The study includes 44 infants with a risk of vertical transmission from the mother and 16 children with haemophilia. No cases were found to be infected by blood-transfusion. Twenty of the 44 infants with congenital HIV-antibodies were HIV-infected. Seven of them died from AIDS, 10 currently have AIDS and three are asymptomatic. Seventeen infants are well and HIV-antibody negative after the age of 18 months. Seven infants still have unclarified status, but all are well. Three of the patients with haemophilia are dead. The 13 others do not have AIDS. It is surprising that most of the infected infants' mothers were not known to be infected before the infants got sick. Thus infected infants exist in families who are not suspected to be HIV-infected. The AIDS-committee of The Danish Society of Paediatrics has proposed recommendations for HIV-testing of infants and children. HIV-infected families need comprehensive psychosocial care. The risk-factor from blood-transfusion is now eliminated, but vertical transmission will continue to be a risk-factor. The size of the problem in Denmark will not be known until an epidemiological study of pregnant women has been conducted.