Acquired Haemophilia A in four north European countries: survey of 181 patients.

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by acquired antibodies against coagulation factor VIII. In the Nordic countries, treatment and outcomes have not been studied in recent times. To collect retrospective data on patients diagnosed with AHA in the Nordic countries between 2006 and 2018 and compare demographic data and clinical outcomes with previously published reports, data were collected by six haemophilia centres: three Swedish, one Finnish, one Danish and one Estonian. The study included 181 patients. Median age at diagnosis was 76 (range 5-99) years, with even gender distribution. Type and severity of bleeding was comparable to that in the large European Acquired Haemophilia Registry study (EACH2). Bleedings were primarily treated with activated prothrombin complex concentrate (aPCC) with a high success rate (91%). For immunosuppressive therapy, corticosteroid monotherapy was used most frequently and this may be the cause of the overall lower clinical remission rate compared to the EACH2 study (57% vs. 72%). Survey data on 181 patients collected from four north European countries showed similar demographic and clinical features as in previous studies on AHA. aPCC was used more frequently than in the EACH2 study and the overall remission rate was lower.

Platelet function testing: Current practice among clinical centres in Northern Europe.

INTRODUCTION: Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing. AIMS: To identify current practice among centres performing platelet function tests in Northern Europe. METHODS: A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million. RESULTS: Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres. CONCLUSIONS: The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Von Willebrand Factor Multimeric Assay in Acquired von Willebrand Disease Diagnosis: A Report of Experience from North Estonia Medical Centre.

Objectives Acquired von Willebrand syndrome (AVWS) is a rare and frequently underdiagnosed bleeding disorder with an unknown prevalence. The diagnosis of AVWS is made based on laboratory investigations and the presence of clinical symptoms. Evaluation and management of affected patients are complex due to the need for multiple laboratory assays. Materials and Methods Here, we describe the clinical and laboratory data of seven patients with a diagnosis of AVWS. All patients met the criteria for AVWS based on laboratory findings, bleeding symptoms, and the absence of any previous history of a bleeding disorder. Results In all cases, the laboratory findings, lack of bleeding anamnesis, and family history suggested the presence of AVWS. Von Willebrand factor multimeric analysis showed decreased high-molecular weight (HMW) multimers in six cases. Patients with lower HMW multimers experienced more severe bleeding complications. Conclusions The diagnosis of AVWS is complex and requires extensive laboratory evaluation. Interdisciplinary collaboration and complex laboratory evaluations are of paramount importance for the early recognition of AVWS and optimal AVWS diagnosis as well as successful clinical management.

Methods for individualising factor VIII dosing in prophylaxis.

Haemophilia A is a sex-linked disorder characterised chiefly by recurrent, spontaneous joint and muscle bleedings resulting from deficiency of factor VIII (FVIII). Recurrent joint bleeds result in haemophilic arthropathy. Unless treated with factor replacement therapy, many patients with severe haemophilia become disabled. The first clinical evidence favouring prophylaxis originated from the studies in Sweden and the Netherlands in the 1960s. Later on, it was shown that prophylaxis could prevent arthropathy, if started early in life, or slow its progression in adults with established arthropathy. The optimal dosing of FVIII in long-term prophylaxis has still not been determined, and there is growing evidence that the dose and frequency of FVIII should be individualised. We conducted a systematic search of PubMed to identify all relevant articles on FVIII prophylaxis in severe haemophilia A. We focused on articles with detailed information about individualisation of prophylaxis. Long-term prophylaxis in haemophilia was introduced in Sweden in the late 1950s. However, standard prophylactic regimens may not be appropriate for all patients with severe haemophilia. Factors such as age, joint status, co-morbidities and differences in pharmacokinetics lead to interindividual variation in factor requirement. Dose tailoring of FVIII by clinical outcome was first described in 1994. Since then, several dose-finding studies questioned the necessity to maintain preinfusion levels of FVIII above 1%. Individualising prophylaxis by dose tailoring is now recommended. Each country should adopt policies for individualising prophylaxis in patients with severe haemophilia. This would lead to a better distribution of the available source of factor concentrates.