Aim The use of musculoskeletal ultrasound (MSK‐US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD‐US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK‐US and the HEAD‐US score. Methods Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross‐sectional study, regardless of their clinical condition, HB severity and treatment received. Two blinded observers were involved in image acquisition and scoring in each centre. Results Eighty‐two patients from 12 centres were enrolled: 27% mild HB, 23% moderate, 50% severe HB. Mean age was 38.9 ± 16.4 years, 60% were treated on demand (OD) and 40% were on prophylaxis. HEAD‐US was zero in all joints in 28.6% OD patients and 36.4% on prophylaxis. Mean scores significantly worsened with HB severity, except for the left knee. Patients on primary and secondary prophylaxis had significantly better joint health vs OD patients in all joints, except the right ankle. Among OD patients, those with severe disease presented significantly worse scores in all HEAD‐US items related to permanent damage. Conclusion Joint status of HB patients in Spain is influenced by severity and treatment modality, related to the development of arthropathy, which appears prevalent in OD patients with severe HB. Routine assessment with an imaging tool such as ultrasound and HEAD‐US system may help to improve joint health by personalizing and adjusting treatment in this population.

SummaryWe studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p <0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p <0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p <0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis.

Vitamin K antagonists (VKAs) remain as the most prescribed drug for treatment and prevention of thrombotic disorders in many countries, despite the recent approval of the new oral anticoagulants (NOACs). Although effectiveness and safety of VKAs are tightly associated to maintaining the patient within the international normalised ratio (INR) therapeutic range (TWR), they have been likened to NOACs when patients are in good INR control (≥66% of TWR). Therefore, assessing the safety of patients should be a priority in the selection of the anticoagulation therapy. The aim of this study was to evaluate the association between CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2*3, ABCB1 C3435T, APOE, CYP2C19*2 and CYP2C19*17 gene polymorphisms and treatment safety in 128 patients diagnosed with atrial fibrillation or venous thromboembolism during the initial first seven months of acenocoumarol therapy. After the first month, VKORC1-T-allele and APOE-E3/E3 genotype were independently associated to higher time above therapeutic range (TAR) and lower time below the therapeutic range (TBR). After seven months, VKORC1 T-allele predicted higher TAR, and was also associated to increased INR>4, particularly the TT-genotype (odds ratio [OR]: 32; 95% confidence interval [CI95%]: 6-175; p=810⁻⁵). C-alleles for CYP2C9*3 (OR: 5.5; CI95%: 1.8-17; p=0.003) and ABCB1 (OR: 8.9;CI95%: 1.1-70; p=0.039) independently influenced on INR>6 . Patients VKORC1-TT/ABCB1-C remained 26.8% [19.7-38.9] TAR, with associated relative risk (RR) for INR>4 1.8 higher (CI95%: 1.2-2.5; p=0.015). Patients VKORC1-TT also presented the highest risk of bleeding events (RR: 3.5;CI95%: 1.4-8.4; p=0,010). In conclusion, VKORC1, CYP2C9*3, APOE and ABCB1 genotypes should be considered in prevention of overanticoagulation and bleeding events in the initiation of acenocoumarol therapy.

The variability in the stable ACN dose was better explained by a pharmacogenetic algorithm including clinical and genetic factors (CYP2C9, VKORC1, and APOE) than by a clinical algorithm, providing a more accurate dosage prediction.