Research projects
Moderate haemophilia
Current treatment of haemophilia is predominantly guided by the severity classification. While patients with severe haemophilia are closely monitored and receive early prophylaxis, moderate and mild patients are monitored less frequently and mostly receive treatment on-demand. The group of moderate haemophilia, however, is heterogeneous with a wide variation in clinical phenotype, with some of the patients having a considerable need for factor substitution. Bleeding phenotype is not strictly correlated to the coagulation factor level, but also influenced by physical activity, presence of target joints and synovial hypertrophy, degree of arthropathy and adherence to a prophylactic regime. According to more recent thinking, haemophilia care and treatment therefore should be tailored individually. The aim of the ongoing PhD project (Ragnhild J Måseide) is to study and evaluate the treatment and outcome of patients with moderate haemophilia A and B (factor level 1-<5 IU/dL) in the Nordic region (Iceland, Sweden, Denmark, Finland and Norway) and our group is the coordinating centre.
Age related comobidities in haemophilia
Rates of hypertension and renal disease, as with other cardiovascular risk factors and comorbidities, are known to rise with age. In haemophilia, it appears from some reports that
there is an even stronger association with hematuria and hypertension. Our group is the coordinating centre for an epidemiologic European multicentre study on behalf of the ADVANCE (Agerelated-DeVelopments-ANd-Comorbidities-in-hemophilia Working Group)
The group is interested in determining, among consecutively screened people with haemophilia ( 800 pts.), aged ≥40 years with a follow up period of 10 years, whether rates of hypertension and renal disease vary according to a previous history of hematuria and whether rates of hypertension/renal disease/ and other cardiovascular and malignant comorbidities vary with specific influencing factors in haemophilia. Two papers form the cross sectional study have already been published and now further followed up in the longitudinal prospective study. Christian Qvigstad is working as a PhD student on this project.
Optimizing bypassing agents.
During the last years we have studied and published papers on how to optimize and tailor treatment in persons with haemophilia with or without inhibitors to FVIII and in persons with FVII deficiency.
One of main objectives has been tailoring of treatment with bypassing agents (BPA) for haemophilia patients with inhibitors. Development of inhibitors is the most serious complications of haemophilia treatment today, High titre inhibitors to factor VIII and less often to factor FIX, represent a major challenge in the treatment of haemophilia A and B. The treatment of bleeds in haemophilia patients with inhibitors relies on the use of the bypassing agents, factor eight bypassing activity (FEIBA) or recombinant factor VIIa. While both therapies are effective in the majority of bleeding episodes and postoperative prophylaxis, there is a significant amount of inter individual variability when it comes to the response to therapy.
In haemophilia patients without inhibitors, there is a close relationship between the level of FVIII or FIX measured ex vivo and the haemostatic outcome of the patients.
However, in inhibitor patients there is no such relationship using bypassing treatment as there is no established laboratory assay to monitor efficacy and optimal dosing.
We are studying the effect of bypassing agents using thromboelastography (TEG/ROTEM) and thrombin generation test (TGA) to individualize coagulation factor concentrate usage and dosing in the home treatment program, individualize coagulation factor concentrate usage and dosing prior to and in the postoperative period, address the issue of minimum effective dose during surgery and apply these assays in the evaluation of the critically ill patient with concomitant haemostatic insufficiency. In addition we have published that adjunct use of tranexamic acid (TXA) to BPA significantly increased the clot stability without increasing the thrombin generation and may be superior to standard treatment with BPA alone.
Reversal of factor Xa inhibitors
Today there are no evaluated effective treatments to reverse the effect of FXa-inhibitors (direct oral anticoagulants (DOAC)). As a PhD project (Nina Haagenrud Schultz) we are performing studies where the objectives are to detect the most effective haemostatic agent and appropriate dose for reversal of bleeds caused by FXa inhibitors extensively used in the clinic for atrial fibrillation and treatment of venous thromboembolism. The effect is assessed mainly by the two global coagulation methods thromboelastography (TEG) and thrombin generation assay (TGA) since conventional coagulation assays such as aPTT and INR are not capable to measure the effect of DOAC accurately. Studies are also performed to investigate the effect of FXa inhibitors on platelet function and endothelium.
Immune thrombocytopenia
Parts of the group is also involved in studies on immune thrombocytopenia ITP and in the RITP trail we aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids. (Lancet 2015; 385: 1653–61). The follow up study PROLONG has now been ongoing for 3 years where we want evaluate the long-term effect of rituximab and immunological changes also including a PhD project on the immunological.
The group also participates in several other international and Nordic investigator initiated research projects on bleeding disorders.