Bleeding Episodes In Haemophilia Patients Research Articles

Early use of recombinant factor VIIa improves mean arterial pressure and may potentially decrease mortality in experimental hemorrhagic shock: a pilot study.

Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and improve survival after experimental hepatic trauma. Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction of mean arterial pressure, animals were blindly randomized to receive intravenous rFVIIa (180 microg/kg) (n = 6) or placebo (n = 7). Mortality was 43% (three of seven) in controls versus 0% with rFVIIa (p = 0.08, chi2). Significantly shorter prothrombin time and higher mean arterial pressures were observed in the rFVIIa group. Intravenous administration of rFVIIa early after induction of hemorrhage shortens prothrombin time and improves mean arterial pressure. A trend toward improved survival was observed.

Early treatment with recombinant factor VIIa results in greater efficacy with less product.

Early treatment of bleeding episodes in haemophilia patients offers advantages over later treatment, including minimizing the damage caused by the haemorrhage and reducing the amount of product needed to control it. Self-administration at home also offers greater convenience and time and cost savings for both patient and physician. We compared the amount of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) used in the treatment of peripheral intramuscular haemorrhages in people with haemophilia A and B with inhibitors and in those with acquired haemophilia, in the compassionate use, dose-finding and US home treatment studies. We also compared the response rates in each of the 3 studies. In the compassionate use setting, in which the mean time from onset of bleeding to initiation of treatment with rFVIIa was 5 d, the mean number of doses given per bleeding episode was 13.6, with 63.1% of episodes without compartment syndrome and 73% with tense muscle/compartment syndrome having an excellent or effective response. In the dose-finding study, average time from onset of bleeding to treatment with rFVIIa was 9 h. The average number of doses given was 3.55, and 72% in the high-dose arm were judged to have an excellent or effective response. In the US home treatment study in which bleeding episodes were treated earlier (mean 1.2 h from onset of bleeding), the mean number of doses given was 2.3, and 92% had an effective response to treatment. These findings indicate that early treatment with rFVIIa has a greater success rate, with fewer doses being required. Home treatment results in cost savings, greater convenience, and less morbidity.

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.

Effects of Hemophilia on Articulations of Children and Adults

The majority of bleeding episodes in hemophilic patients occur within the joints. Of these hemarthroses, the knees, elbows, and ankles account for almost 80%. Should the bleeding persist, the synovium starts to hypertrophy and a vicious cycle of chronic synovitis develops, leading to joint destruction. In immature articulation, synovitis causes hypertrophy of the epiphyseal growth plates and significant structural deficiencies may rapidly develop. This stimulus to the growth plates results in bone hypertrophy, leg length discrepancy, and angular deformities. In mature articulation, hemophilia has a major detrimental effect on the joint cartilage. As it progressively exacerbates, joint function deteriorates. Loss of joint space is the most important radiographic finding related to range of motion. As the synovium becomes increasingly scarred, there is gradual conversion from friable hyperemic tissue to fibrotic scar tissue. This process is the natural course of hemophilic arthropathy. A phenomenon in adult hemophilic patients is that their joints, which radiographically appear severely destroyed, seem to function reasonably well for many years.