1.
Epidemiological Challenges in Rare Bleeding Disorders: FVIII Inhibitor Incidence in Haemophilia A Patients-A Known Issue of Unknown Origin
Keipert C, Drechsel-Bäuerle U, Oberle D, Müller-Olling M, Hilger A
International journal of environmental research and public health. 2020;18(1)
Abstract
There is a broad range of factor products approved in Germany for haemophilia A treatment. Since the introduction of recombinant coagulation factor VIII (FVIII) products in the 1990s, there has been substantial debate whether there is a difference in inhibitor incidence between single FVIII products or product classes. Neither haemophilia registries nor clinical studies, including a randomised controlled clinical trial, provided a consistent and definite answer. The reasons were mainly related to methodological challenges in conducting controlled studies in a rare disease. In this analysis, the most relevant epidemiological challenges and main problems were examined, including study bias, potential overlap of individual studies and advanced development of therapy and methods in the course of time. Meta-analyses on two levels showed that therapies using recombinant products resulted in different event rates when compared to plasma-derived products. These results are accompanied by substantial study heterogeneity evidenced by Cochran's Q tests. Only three studies have been identified that meet the standards of current clinical guidance. To finally resolve this ongoing and disputable safety issue of replacement therapy, collaboration among registry owners, academia and regulators must be fostered.
2.
Mortality, Morbidity and Related Outcomes Following Perioperative Blood Transfusion in Patients with Major Orthopaedic Surgery: A Systematic Review
Muller S, Oberle D, Drechsel-Bauerle U, Pavel J, Keller-Stanislawski B, Funk MB
Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 2018;45((5):):355-367.
Abstract
Background: Benefits and risks of liberal and restrictive transfusion regimens are under on-going controversial discussion. This systematic review aimed at assessing both regimens in terms of pre-defined outcomes with special focus on patients undergoing major orthopaedic surgery. Methods: We performed a literature search for mortality, morbidity and related outcomes following peri-operative blood transfusion in patients with major orthopaedic surgery in electronic databases. Combined outcome measure estimates were calculated within the scope of meta-analyses including randomised clinical trials comparing restrictive versus liberal blood transfusion regimens (e.g. MH risk ratio, Peto odds ratio). Results: A total of 880 publications were identified 15 of which were finally included (8 randomised clinical trials (RCTs) with 3,693 patients and 6 observational studies with 4,244,112 patients). Regarding RCTs, no significant differences were detected between the transfusion regimes for all primary outcomes (30-day mortality, thromboembolic events, stroke/transitory ischaemic attack, myocardial infarction, wound infection and pneumonia) and a secondary outcome (length of hospital stay), whereas there was a significantly reduced risk of receiving at least one red blood concentrate under a restrictive regimen. Conclusion: The results of this systematic review do not suggest an increased risk associated with either a restrictive or a liberal transfusion regimen in patients undergoing major orthopaedic surgery.