Assay discrepancy in mild haemophilia A: entire population study in a National Haemophilia Centre.

Assay discrepancy in mild haemophilia, here defined by a significantly higher factor VIII (FVIII):C response by the one-stage procoagulant assay as compared with a two-stage enzymatic method, has repeatedly been reported in literature. The purpose of this study was to determine the overall prevalence of this phenomenon amongst mild haemophilia families from a population of 2.95 million inhabitants in the Western Danish region. Information was collected retrospectively through a thorough search of archives of the National Haemophilia Centre in Aarhus. We identified 109 patients with mild haemophilia A amongst whom 92 were eligible to enter the study. These represent a total of 53 unrelated families. Our data illustrate that this assay discrepancy pattern is found quite frequently amongst our mild haemophilia A families. While the ratio of FVIII:C chromogenic/FVIII:C clot values was quite consistent amongst patients belonging to same family pattern, ratios in the entire cohort of families ranged from 0.18 to 1.00. Selecting a cut-off level for the FVIII:C chromogenic/FVIII:C clot ratios at 0.7, 0.6 and 0.5, respectively, we found that 38 (72%), 27 (51%) and 19 (36%) of families, respectively, displayed this assay discrepancy. In 10 patients, the FVIII:C chromogenic level was inside the category of moderate haemophilia at >0.01-<0.05 IU mL(-1), pointing to a class-shift in the biochemical phenotype. In conclusion, our data illustrate a substantial prevalence of the assay discrepancy phenomenon amongst mild haemophilia A patients in our geographical area.

Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia.

It is well known that teenagers with chronic diseases have problems complying with their treatment. The aim of this study was to evaluate the patient's knowledge of haemophilia and his compliance to prophylactic treatment, and the age at which the patient took over the responsibility for his disease and to create educational material for teenagers and adolescents. This was a prospective multicentre study performed in Hemophilia Treatment Centres in Scandinavia. A total of 108 of 134 patients, between 13 and 25 years completed the questionnaire, a response rate of 80%. Eighty-three patients had a severe form of haemophilia, 24 patients in moderate form and one patient did not know the severity of his disease. Seventy-eight patients were on prophylactic treatment. The median age for starting prophylactic treatment was 3.0 years and the median age for the patient performing venepuncture was 11.6 years. Sixty-seven of 78 patients knew that the best time to give prophylactic treatment was in the morning. Even though the patients were on prophylactic treatment, 47 of 78 patients took additional treatment before sports activities. At a mean age of 14.1 years the patient himself had the responsibility for his disease and treatment. In the cohort of 108 patients, 73 were aware of their haemophilia heredity. This study shows a rather high degree of knowledge of haemophilia and compliance with treatment among the patients but it is of great importance for the nurse to continuously improve the patient's compliance and keep him aware of the benefit of regular treatment for his future well being.

Home treatment with recombinant activated factor VII: results from one centre.

Haemophilia patients developing an inhibitor against factor VIII (FVIII) or FIX require alternative treatment for the management of their bleeding, rather than standard procedures. In patients with low titre inhibitors, increased doses of FVIII or FIX may improve haemostasis. If a higher titre is present, a porcine FVIII concentrate may be efficacious in selected cases. 'Bypassing' agents, such as low purity FIX concentrates, or activated or unactivated concentrates of prothrombin complex may also be useful in inhibitor patients. An activated factor VII molecule (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), has been produced by recombinant DNA cell technology. In June 1994, we established a home treatment programme with rFVIIa for five inhibitor patients to study its efficacy in the early intervention of bleeding episodes; our results from the first 3 years are presented. Self-treatment in the home took place in 50 instances of acute minor bleeding. A mean of 2.02 doses of rFVIIa (each dose of about 90 microg/kg bodyweight) was required to arrest bleeding (range 1-4 doses). Four bleeding episodes required in-hospital management either because the acute condition was caused by severe trauma, or because treatment had not been instituted in the early phase of bleeding. Here, the range of rFVIIa doses was 4-37. For comparison, we also report 36 minor bleeding episodes managed in-hospital in three of these five patients who participated in the Compassionate Use Study where home treatment was not permitted. These bleeding episodes required considerably more administrations of rFVIIa with a mean consumption of 8 doses in joint bleeds and 9.5 doses in muscle and soft tissue bleeds. In conclusion, we feel that our home treatment results strongly suggest that early intervention by home treatment with rFVIIa in acute minor bleeding is efficacious and cost effective.

Approaches towards successful home treatment in patients with inhibitors.

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.