Routine prophylactic treatment in patients with von Willebrand disease (VWD) seems to reduce the risk of spontaneous bleeds, epistaxis, and hospitalisations, but there is a need for more randomised controlled trials to determine the magnitude of these benefits as evidence is generally of low quality, researchers have concluded.
An international team undertook a systematic review of literature evidence on clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleeding, using MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL).
Their review, published in the journal Haemophilia, included 12 studies. Of these, one placebo-controlled randomised clinical trial (RCT) showed with low certainty evidence that VWD prophylaxis (regular administration of coagulation factor) reduced the rate of bleeding episodes (rate ratio [RR] of 0.24) versus placebo, while four other studies, which looked at data from before and after prophylactic treatment, also indicated that VWD prophylaxis reduced the rate of bleeding (RR 0.34; very low certainty evidence).
The RCT also showed that epistaxis (RR 0.38; moderate certainty) and rates of hemarthrosis (RR 0.50; low certainty) were reduced with prophylactic treatment compared to placebo, but that such treatment might increase the risk of serious adverse events (RR 0.34, low certainty).
In addition, the researchers noted that the time to first bleeding was also shown to be delayed in the RCT participants taking prophylactic treatment: 31.4 days longer when compared with no prophylaxis (moderate certainty evidence), while one observational study with comparative data showed, with very low certainty evidence, that the median rate of heavy menstrual bleeding per patient per year decreased by nine episodes.
With regard to the effect on hospitalisation, the review found that one observational study with comparative data reported on this as rate of event per patient, and showed (with very low certainty evidence) that prophylactic treatment might lower the rate of hospitalisations (RR 0.64).
The researchers concluded that based on largely low-certainty evidence, “VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalisations,” but that “more RCTs should be conducted to increase the certainty in these benefits with focus on the relative efficacy for the more common bleeding of hemarthroses and epistaxis”, and thus help inform better decision-making.
“While there were several [observational studies] reporting on prophylaxis in patients with VWD, the patient burden of receiving prophylaxis weighted with the benefits of prophylaxis is poorly reported in literature making implications for clinical practise restricted,” they wrote.
They also noted that their findings are limited by the articles and study design of those included in the review, and by the fact that they were not able to include any assessing quality of life and cost-effectiveness.