Health-related quality of life and physical activity in Nordic patients with moderate haemophilia A and B (the MoHem study).

INTRODUCTION: The impact of moderate haemophilia on health-related quality of life (HRQoL) and physical activity (PA) is not well known. In previous studies, persons with factor VIII/factor IX activity (FVIII/FIX:C) below 3 IU/dL were associated with a more severe bleeding phenotype than predicted. AIM: To explore HRQoL and PA in patients with moderate haemophilia A (MHA) and B (MHB). METHODS: A cross-sectional, multicentre study covering patients with MHA and MHB in Sweden, Finland, and Norway. HRQoL was assessed with the EuroQoL 5-Dimensions (EQ-5D) form and PA with the International Physical Activity Questionnaire among participants aged ≥15 years. RESULTS: We report on 104 patients aged 15-84 years from the MoHem study. Overall, EQ-5D utility was .85 (median) (Q1-Q3 0.73-1.0) with corresponding visual analogue scale (VAS) 80 (70-90), which were similar regardless of treatment modality, FVIII/FIX:C, and MHA or MHB. Pain and mobility were most frequently affected dimensions. Utility (r = -.54), VAS (r = -.42), and PA (r = -.32) correlated negatively with arthropathy (HJHS). Only patients aged 41-50 years displayed lower utility (p = .02) and VAS (p < .01) than the Norwegian population norm. Patients on prophylaxis aged 35-54 years reported higher PA than those treated on-demand (p = .01). CONCLUSION: Haemophilic arthropathy had negative impact on HRQoL and PA in Nordic patients with moderate haemophilia. Middle-aged patients captured lower utility and VAS than observed in the general population. Tailored prophylaxis and improved joint health may influence positively on HRQoL and PA also in moderate haemophilia.

Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B.

BACKGROUND: Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with hemophilia B (PwHB) introduces challenges for clinical management. AIM: To study the differences in FIX:C using OSA and CSA in moderate and mild hemophilia B (HB), their impact on classification of severity, and correlation with genotype. METHODS: Single-center study including 21 genotyped and clinically characterized PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories. RESULTS: FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with diluted normal plasma, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories. CONCLUSION: FIX:C was consistently higher by OSA compared with the CSA. Assessing FIX:C by CSA alone would have led to diagnosis of a more severe hemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.

Ultra-processed food intake and incident venous thromboembolism risk: Prospective cohort study.

BACKGROUND & AIMS: Ultra-processed food (UPF) intake has been associated with multiple health outcomes, but data on the association between UPF intake and venous thromboembolism (VTE) risk are lacking. We conducted this study to examine the association between UPF intake and the risk of incident VTE. METHODS: This prospective cohort study was based on 186,323 participants free of baseline VTE from the UK Biobank. UPF intake was assessed by 24-h recall questionnaires. Data on incident VTE came from the nationwide inpatient and primary care datasets and the death registry. Cox proportional hazards regression was used to estimate the association between UPF intake and incident VTE risk. Multiplicative interactions and stratified analyses by age, sex, and body mass index were performed. RESULTS: During a 10.5-year (median) follow-up, 4235 incident VTE cases were diagnosed. After adjusting for covariates, the hazard ratio of VTE among individuals with the highest quintile of UPF intake was 1.05 (95% confidence interval [CI] 0.94, 1.17) for UPF in servings, 1.12 (95% CI 1.01, 1.24) in grams, 1.10 (95% CI 1.00, 1.22) in grams %, 1.21 (95% CI 1.10, 1.33) in energy, and 1.15 (95% CI 1.05, 1.27) in energy % compared to those in the lowest quintile. Age, sex, and body mass index did not modify the associations (Pinteraction > 0.05). CONCLUSIONS: Higher UPF intake was associated with a moderately increased risk of VTE.

Association of ABO blood groups with venous thrombosis recurrence in middle-aged patients: insights from a weighted Cox analysis dedicated to ambispective design.

BACKGROUND: In studies of time-to-events, it is common to collect information about events that occurred before the inclusion in a prospective cohort. When the studied risk factors are independent of time, including both pre- and post-inclusion events in the analyses, generally referred to as relying on an ambispective design, increases the statistical power but may lead to a selection bias. In the field of venous thromboembolism (VT), ABO blood groups have been the subject of extensive research due to their substantial effect on VT risk. However, few studies have investigated their effect on the risk of VT recurrence. Motivated by the study of the association of genetically determined ABO blood groups with VT recurrence, we propose a methodology to include pre-inclusion events in the analysis of ambispective studies while avoiding the selection bias due to mortality. METHODS: This work relies on two independent cohorts of VT patients, the French MARTHA study built on an ambispective design and the Dutch MEGA study built on a standard prospective design. For the analysis of the MARTHA study, a weighted Cox model was developed where weights were defined by the inverse of the survival probability at the time of data collection about the events. Thanks to the collection of information on the vital status of patients, we could estimate the survival probabilities using a delayed-entry Cox model on the death risk. Finally, results obtained in both studies were then meta-analysed. RESULTS: In the combined sample totalling 2,752 patients including 993 recurrences, the A1 blood group has an increased risk (Hazard Ratio (HR) of 1.18, p = 4.2 × 10-3) compared with the O1 group, homogeneously in MARTHA and in MEGA. The same trend (HR = 1.19, p = 0.06) was observed for the less frequent A2 group. CONCLUSION: The proposed methodology increases the power of studies relying on an ambispective design which is frequent in epidemiologic studies about recurrent events. This approach allowed to clarify the association of ABO blood groups with the risk of VT recurrence. Besides, this methodology has an immediate field of application in the context of genome wide association studies.

Plasma protein and venous thromboembolism: prospective cohort and mendelian randomisation analyses.

We conducted cohort and Mendelian randomisation (MR) analyses to examine the associations of circulating proteins with risk of venous thromboembolism (VTE) to provide evidence basis for disease prevention and drug development. Cohort analysis was performed in 11 803 participants without baseline VTE. Cox regression was used to estimate the associations between 257 proteins and VTE risk. A machine-learning model was constructed to compare the importance of identified proteins and traditional risk factors. Genetic association data on VTE were obtained from a genome-wide meta-analysis (26 066 cases and 624 053 controls) and FinnGen (14 454 cases and 294 700 controls). The cohort analysis, including 353 incident VTE cases diagnosed during a 6.6-year follow-up, identified 21 proteins associated with VTE risk after false discovery rate correction. The machine-learning model indicated that body mass index and von Willebrand factor (vWF) made the same as well as most of the contributions to the overall model prediction. MR analysis found that genetically predicted levels of vWF, SERPINE1 (plasminogen activator inhibitor 1, known as PAI-1), EPHB4 (ephrin type-B receptor 4), TYRO3 (tyrosine-protein kinase receptor TYRO3), TNFRSF11A (tumour necrosis factor receptor superfamily member 11A), and BOC (brother of CDO) were causally associated with VTE risk.

No difference in quality of life between persons with severe haemophilia A and B.

INTRODUCTION: Good health-related quality of life (HRQoL) is an important goal in the treatment of persons with haemophilia B (PwHB). Studies focusing on this population are limited, however, and data are insufficient. AIM: To assess the HRQoL in PwHB and to compare this to data on persons with haemophilia A (PwHA), as well as to evaluate the impact of joint health on HRQoL and to identify areas of insufficient care. METHODS: The B-NORD study enrolled persons with severe haemophilia B and matched controls with haemophilia A. HRQoL was assessed using the EQ-5D-3L questionnaire and joint health using Haemophilia Joint Health Score 2.1 (HJHS). RESULTS: The EQ-5D-3L was completed by 63 PwHB and 63 PwHA. Mobility problems were reported by 46% of PwHB and 44% of PwHA, pain/discomfort by 62% and 56%, and anxiety/depression by 33% and 17%, respectively. No significant difference was observed between PwHA and PwHB in EQ-5D profiles, level sum score, EQ-5D index (PwHB mean .80, PwHA mean .83, p = .24), or EQ VAS score (PwHB: mean 70, PwHA: mean 77, p = .061). Linear regression adjusted for age demonstrated that an increase in HJHS score was associated with a significant decrease in both EQ-5D index (B -.003, R2 .22) and EQ VAS score (B -.37, R2 .17). CONCLUSION: Despite the majority of patients being treated with prophylaxis, impaired HRQoL was reported in both PwHB and PwHA. No differences in HRQoL were found between the two groups. Impaired joint health had a significant negative impact on HRQoL.

Plasma Phospholipid Fatty Acids and Risk of Venous Thromboembolism: Mendelian Randomization Investigation.

Circulating fatty acids may affect thrombosis but epidemiological data on the associations between fatty acids and risk of venous thromboembolism (VTE) are limited and conflicting. We conducted a Mendelian randomization study to examine the causal associations of 10 circulating fatty acids with VTE risk. Genetic variants strongly associated with ten fatty acids and without linkage disequilibrium were selected as instrumental variables from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Genetic associations for VTE and its subtypes were obtained from the International Network Against Venous Thrombosis Consortium (30,234 cases and 172,122 controls) and the FinnGen study (11,288 VTE cases and 254,771 controls). Estimates from the two data sources were combined. Per standard deviation increase in genetically predicted fatty acid levels, the combined odds ratio (OR) of VTE was 0.88 (95% confidence interval [CI] 0.84-0.92) for α-linolenic acid, 0.92 (95% CI 0.90-0.95) for linoleic acid, 0.85 (95% CI 0.78-0.92) for palmitoleic acid, 0.77 (95% CI 0.77-0.84) for oleic acid, 1.16 (95% CI 1.10-1.23) for eicosapentaenoic acid, 1.10 (95% CI 1.06-1.14) for docosapentaenoic acid, 1.06 (95% CI 1.04-1.08) for arachidonic acid, and 1.19 (95% CI 1.11-1.28) for stearic acid. Genetically predicted levels of docosahexaenoic acid or palmitoleic acid were not associated with VTE risk. Four and eight out of ten genetically predicted fatty acid levels were associated with risk of pulmonary embolism and deep vein thrombosis, respectively. This study suggests that strategies targeting at fatty acids may act as prevention approaches for VTE.

Markers of neutrophil activation and neutrophil extracellular traps in diagnosing patients with acute venous thromboembolism: A feasibility study based on two VTE cohorts.

BACKGROUND: Venous thromboembolism (VTE) diagnosis would greatly benefit from the identification of novel biomarkers to complement D-dimer, a marker limited by low specificity. Neutrophil extracellular traps (NETs) have been shown to promote thrombosis and could hypothetically be used for diagnosis of acute VTE. OBJECTIVES: To assess the levels of specific markers of neutrophil activation and NETs and compare their diagnostic accuracy to D-dimer. METHODS: We measured plasma levels of neutrophil activation marker neutrophil elastase (NE), the NET marker nucleosomal citrullinated histone H3 (H3Cit-DNA) and cell-free DNA in patients (n = 294) with suspected VTE (pulmonary embolism and deep vein thrombosis) as well as healthy controls (n = 30). A total of 112 VTE positive and 182 VTE negative patients from two prospective cohort studies were included. RESULTS: Higher levels of H3Cit-DNA and NE, but not cell-free DNA, were associated with VTE. Area under receiver operating curves (AUC) were 0.90 and 0.93 for D-dimer, 0.65 and 0.68 for NE and 0.60 and 0.67 for H3Cit-DNA in the respective cohorts. Adding NE and H3Cit-DNA to a D-dimer based risk model did not improve AUC. CONCLUSIONS: Our study demonstrates the presence of neutrophil activation and NET formation in VTE using specific markers. However, the addition of NE or H3Cit-DNA to D-dimer did not improve the discrimination compared to D-dimer alone. This study provides information on the feasibility of using markers of NETs as diagnostic tools in acute VTE. Based on our findings, we believe the potential of these markers are limited in this setting.

Factor IX antibodies and tolerance in hemophilia B in the Nordic countries - The impact of F9 variants and complications.

INTRODUCTION: The development of inhibitory antibodies (inhibitors) in persons with hemophilia B (PwHB) causes significant morbidity. Data on the impact of the F9 variant and immune tolerance induction (ITI) outcome are limited. The aim of this study was to investigate the presence of neutralizing and non-neutralizing antibodies (NNA) in severe hemophilia B (HB) and to evaluate ITI outcome and complications in relation to the pathogenic F9 variant. MATERIALS AND METHODS: Persons with severe HB in the Nordic countries were enrolled and information on F9 variants, inhibitors, ITI and complications were collected. Analyses of anti-FIX antibodies with a fluorescence-immunoassay (xFLI) and an ELISA method were conducted. RESULTS: Seventy-nine PwHB were enrolled. Null variants were seen in 33 (42 %) PwHB and 12 (15 %) had a current or former inhibitor. Eleven (92 %) of the inhibitor patients had experienced allergic manifestations and three (25 %) nephrotic syndrome. Of 10 PwHB with at least one ITI attempt, eight (80 %) were considered tolerant at enrolment. Immunosuppression was included in seven of eight successful or partially successful attempts. Five PwHB had at least one ITI failure before a successful or partially successful ITI. No NNA could be identified. CONCLUSION: A high proportion of severe F9 gene defects among persons with severe HB in the Nordic countries may explain the observed relatively high prevalence of inhibitors. ITI success was independent of the F9 variant and attained despite allergic manifestations and previous ITI failures. Inclusion of immunosuppression tentatively enhances the chances of ITI success. No NNA were observed.

Anti-inflammatory diet and incident peripheral artery disease: Two prospective cohort studies.

BACKGROUND & AIMS: Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the anti-inflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation. METHODS: The study was based on two cohorts of 82 295 Swedish adults aged 45-83 years (38 823 women from Swedish Mammography Cohort and 45 472 men from Cohort of Swedish Men). An anti-inflammatory diet index (AIDI; 0-17 scores) was used to estimate the anti-inflammatory potential of diet. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Over a median 22-year (interquartile range 7.5 years) follow-up period, 3413 PAD cases were ascertained. Compared with individuals in the lowest quartile of the AIDI (score ≤4), the HR of PAD for those in the highest quartile (score ≥8) was 0.84 (95% CI, 0.74-0.94). The inverse association was observed in current and past smokers but not in never smokers. The HR of PAD comparing extreme quartiles of the AIDI was 0.67 (95% CI, 0.53-0.86) in current smoker, 0.78 (95% CI, 0.63-0.97) in past smoker, and 1.00 (95% CI, 0.82-1.23) in never smokers. Among foods included in AIDI, high consumption of breakfast cereals, chocolate, red wine, and olive/canola oil, and low consumption of processed red meat and organ meats were associated with low PAD risk. CONCLUSIONS: The study suggests that adherence to a diet with high anti-inflammatory potential may lower PAD risk, especially in smokers.

Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation.

Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10-8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

In-hospital cardiac arrest due to pulmonary embolism - Treatment and outcomes in a Swedish cohort study.

OBJECTIVES: Pulmonary embolism (PE) constitutes one of the reversible causes of cardiac arrest. The prognosis for PE-related cardiac arrest is poor. Some previous studies have suggested a higher survival rate in patients with PE-related cardiac arrest who receive thrombolysis. No such study has focused on in-hospital cardiac arrests (IHCA). AIM: To describe the prevalence of PE-related IHCA and the characteristics of those patients, as well as to describe favourable and adverse outcomes after thrombolysis. MATERIAL AND METHODS: All patients ≥ 18 years who experienced an IHCA at Karolinska University Hospital between 2007 and 2020 with PE as the primary cause of IHCA were included. Patients were identified from the Swedish Registry for Cardiopulmonary Resuscitation (SRCR). Data was collected from the SRCR and medical records. The primary outcome was survival to discharge. Secondary outcomes were alive at the end of CPR, major bleeding, and minor bleeding. RESULTS: Out of 2,128 IHCA patients, 64 (3%) had a PE-related IHCA of whom 16 (25%) had thrombolysis. A significant association was seen between thrombolysis and survival to discharge (44 % vs 8 %, p-value < 0.01). Major bleeding was not seen in any patient. CONCLUSION: Pulmonary embolism is an uncommon cause of IHCA, and thrombolysis is often not administered in such patients. Thrombolysis may increase survival to hospital discharge, and among the selected patients treated with thrombolysis in our study, there was no apparent major bleeding.

Cardiometabolic, Lifestyle, and Nutritional Factors in Relation to Varicose Veins: A Mendelian Randomization Study.

Background We conducted a 2-sample Mendelian randomization study to assess the associations of cardiometabolic, lifestyle, and nutritional factors with varicose veins. Methods and Results Independent single-nucleotide polymorphisms associated with height (positive control), body mass index, type 2 diabetes, diastolic and systolic blood pressure, smoking, alcohol and coffee consumption, 7 circulating vitamins (A, B6, B9, B12, C, 25-hydroxyvitamin D, and E), and 5 circulating minerals (calcium, iron, magnesium, selenium, and zinc) at the genome-wide significance level were used as instrumental variables. Summary-level data for the genetic associations with varicose veins were obtained from the UK Biobank (8763 cases and 352 431 noncases) and the FinnGen consortium (13 928 cases and 153 951 noncases). Genetically predicted higher height, body mass index, smoking, and circulating iron levels were associated with an increased risk of varicose veins. The odds ratios (ORs) per 1-SD increase in the exposure were 1.34 (95% CI, 1.25-1.43) for height, 1.39 (95% CI, 1.27-1.52) for body mass index, 1.12 (95% CI, 1.04-1.22) for the prevalence of smoking initiation, and 1.24 (95% CI, 1.16-1.33) for iron. Higher genetically predicted systolic blood pressure and circulating calcium and zinc levels were associated with a reduced risk of varicose veins, whereas the association for systolic blood pressure did not persist after adjustment for genetically predicted height. The OR was 0.75 (95% CI, 0.62-0.92) per 1-SD increase in calcium levels and 0.97 (95% CI, 0.95-0.98) for zinc. Conclusions This study identified several modifiable risk factors for varicose veins.

Anti-inflammatory diet and venous thromboembolism: Two prospective cohort studies.

BACKGROUND AND AIMS: Inflammation has been revealed to facilitate thrombogenesis and to increase the risk of venous thromboembolism (VTE). However, limited data are available on the association between the anti-inflammatory diet and incident VTE. We conducted a cohort analysis to examine this association and to further examine whether this association is modified by smoking status, a trigger of systemic inflammation. METHODS AND RESULTS: We used data from two cohorts including 81,507 middle-aged and older Swedish adults without previous VTE at baseline. An empirically validated anti-inflammatory diet index (AIDI), based on 12 foods with anti-inflammatory potential and 5 foods with pro-inflammatory potential, was employed to estimate the anti-inflammatory potential of diet. Hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), of VTE were estimated by Cox proportional hazards regression models. During a mean follow-up of 17.8-years, 5241 VTE cases were diagnosed. Compared with individuals in the lowest quartile of the AIDI (score ≤4), those in the highest quartile (score ≥8) had a 9% (95% CI, 0-17%) lower risk of VTE. The inverse association was observed in current and past smokers (HR between the two extreme quartiles, 0.80, 95% CI, 0.70-0.91) but not in never smokers (HR, 1.03, 95% CI, 0.91-1.17). French fries (HR per serving, 1.33, 95% CI, 1.06, 1.67) but no other foods included in AIDI was associated with VTE. CONCLUSION: The study suggests that a consumption of foods with high anti-inflammatory potential may play a role in the prevention of VTE in smokers.

Platelet Count Rose While D-Dimer Levels Dropped as Deaths and Thrombosis Declined-An Observational Study on Anticoagulation Shift in COVID-19.

BACKGROUND: High levels of D-dimer and low platelet counts are associated with poor outcome in coronavirus disease 2019 (COVID-19). As anticoagulation appeared to improve survival, hospital-wide recommendations regarding higher doses of anticoagulation were implemented on April 9, 2020. OBJECTIVES: To investigate if trends in D-dimer levels and platelet counts were associated with death, thrombosis, and the shift in anticoagulation. METHODS: Retrospective cohort study of 429 patients with COVID-19 at Karolinska University Hospital. Information on D-dimer levels and platelet counts was obtained from laboratory databases and clinical data from medical records. RESULTS: Thirty-day mortality and thrombosis rates were 19% and 18%, respectively. Pulmonary embolism was common, 65/83 (78%). Increased D-dimer levels in the first week in hospital were significantly associated with death and thrombosis (odds ratio [OR]: 6.06; 95% confidence interval [CL]: 2.10-17.5 and 3.11; 95% CI: 1.20-8.10, respectively). If platelet count increased more than 35 × 109/L per day, the mortality and thrombotic risk decreased (OR: 0.16; 95% CI: 0.06-0.41, and OR: 0.36; 95% CI: 0.17-0.80). After implementation of updated hospital-wide recommendations, the daily mean significantly decreased regarding D-dimer levels while platelet counts rose; -1.93; 95% CI: -1.00-2.87 mg/L FEU (fibrinogen-equivalent unit) and 65; 95% CI: 54-76 ×109/L, and significant risk reductions for death and thrombosis were observed; OR: 0.48; 95% CI: 0.25-0.92 and 0.35; 95% CI: 0.17-0.72. CONCLUSION: In contrast to D-dimer levels, increase of platelet count over the first week in hospital was associated with improved survival and reduced thrombotic risk. The daily mean levels of D-dimer dropped while the platelet counts rose, coinciding with increased anticoagulation and a decline in thrombotic burden and mortality.

Lifestyle factors and venous thromboembolism in two cohort studies.

INTRODUCTION: Evidence on the associations of lifestyle factors with venous thromboembolism (VTE) is inconsistent. We aimed to investigate the associations of modifiable lifestyle factors with VTE in women and men. METHODS: We used data from two cohorts comprising 30,137 women and 36,193 men aged over 45 years and free of cancer and VTE. Information on lifestyle factors was collected in 1997 via a self-administrated questionnaire. VTE cases were ascertained by linkage with the National Patient Register until the end of 2019. RESULTS: During a mean of 16.9-years follow-up, 1784 women and 2043 men were diagnosed with VTE. Compared with individuals with <10 min/day of physical activity, the multivariable hazard ratios (HRs) of VTE were 0.67 (95% confidence interval (CI), 0.58, 0.79) and 0.78 (95% CI, 0.67, 0.92) in women and men with >60 min/day, respectively. Compared with individuals with the lowest adherence to a modified Dietary Approaches to Stop Hypertension diet, the multivariable HRs of VTE were 0.87 (95% CI, 0.75, 0.99) and 0.88 (95% CI, 0.80, 1.00) for women and men with the highest adherence. In women, the multivariable HRs of VTE were 1.16 (95% CI, 1.03, 1.29) for past smoker and 1.28 (95% CI, 1.14, 1.45) for current smoker compared with never smoker. Alcohol and coffee consumption were not associated with VTE. CONCLUSIONS: This study suggests that being physically active and adhering to a healthy diet may lower the risk of VTE in women and men. Cigarette smoking was positively associated with VTE in women.

Impaired Fibrinolysis in the Antiphospholipid Syndrome.

The pathogenesis of the antiphospholipid syndrome (APS) is complex and involves the persistent presence of antiphospholipid antibodies (aPL) in the bloodstream causing a prothrombotic condition. aPL induce excessive activation of the endothelium, monocytes, and platelets in consort with aberrations in hemostasis/clotting, fibrinolytic system, and complement activation. Impaired fibrinolysis has been found in APS patients with thrombotic as well as obstetric manifestations. Increased levels of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, together with the presence of aPL against annexin-2, tissue-type plasminogen activator, and plasminogen contribute to the compromised fibrinolytic activity in these patients. Furthermore, unfavorably altered fibrin morphology, less amenable to fibrinolysis, has been proposed as a novel prothrombotic mechanism in APS. This review aims to summarize the present knowledge of the mechanisms involved in impaired fibrinolysis in APS patients. We also present a case from clinical practice as an illustration of fibrinolysis impairment in APS patients from a real-life setting.

Treatment outcomes in persons with severe haemophilia B in the Nordic region: The B-NORD study.

INTRODUCTION: Data on outcome in persons with haemophilia B (PwHB) are limited and mainly extrapolated from studies of haemophilia A (HA). AIM: To characterize treatment outcomes in persons with severe HB in the Nordic region, with a focus on joint health, compared with matched controls with HA. METHODS: PwHB attending haemophilia centres in Denmark, Finland, Norway and Sweden were enrolled and matched with controls with HA. Joint assessment using Haemophilia Joint Health Score (HJHS) and ultrasound according to Haemophilia Early Arthropathy Detection protocol (HEAD-US) was conducted. Adherence was evaluated using the Validated Haemophilia Regimen Treatment Adherence Scale (VERITAS). RESULTS: Seventy-nine males with HB, with median age of 30 years (range 1-75), were enrolled. Eleven patients (14%) had a history of or current inhibitor. Twenty-nine PwHB (37%) reported joint bleeds during the prior year, and 35% had previously undergone joint surgery. Ninety-five per cent were on prophylaxis, and 70% used recombinant concentrates, with a median factor consumption of 3,900 IU/kg/year for standard half-life products. Only two patients had a VERITAS score corresponding to 'non-adherence'. Joint health, assessed with HJHS, showed a significant lower score among PwHB compared with HA controls, explained by a difference in the 18-49 age group, without observed differences in older or younger subgroups. The HEAD-US scores were overall low. CONCLUSION: The Nordic cohort of PwHB is well treated by prophylaxis, but the goal of zero bleeds for all is not reached. Our findings suggest that patients with severe HB suffer from a milder arthropathy than patients with severe HA.

Haemophilia early arthropathy detection with ultrasound and haemophilia joint health score in the moderate haemophilia (MoHem) study.

INTRODUCTION: Detection of early arthropathy is crucial for the management of haemophilia, but data on moderate haemophilia are limited. Therefore, we evaluated joint health and treatment modalities in Nordic patients with moderate haemophilia A (MHA) and B (MHB). AIM: To explore and compare the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) and Haemophilia Joint Health Score (HJHS) to detect early arthropathy in moderate haemophilia. METHODS: A cross-sectional, multicentre study covering Nordic patients with MHA and MHB. Arthropathy was evaluated by HEAD-US and HJHS 2.1. RESULTS: We assessed 693 joints in 118 patients. HEAD-US scores (medians [interquartile ranges]) were as follows: elbows 0 points (0-0), knees 0 (0-0) and ankles 0 (0-1). Respectively, by HJHS: elbows 0 (0-1), knees 0 (0-1) and ankles 0 (0-1). Cartilage (14%) and bone (13%) were most commonly affected by HEAD-US. Frequent HJHS findings were crepitus on motion in knees (39%), and loss of flexion (23%) and extension (13%) in ankles. HEAD-US correlated strongly with HJHS (elbows r = .70, knees r = .60 and ankles r = .65), but 24% had discordant scores. Joints with HJHS zero points, 5% captured HEAD-US ≥1 point. Moreover, 26% had HJHS findings without HEAD-US pathology. Notably, 31% of knees had crepitus on motion and normal HEAD-US. CONCLUSION: Overall, the joints attained low scores implying good joint health. HEAD-US correlated strongly with HJHS. In 5%, HEAD-US detected subclinical pathology. Crepitus on motion was frequently reported despite normal HEAD-US, thus not necessarily reflecting arthropathy. HEAD-US therefore improves the joint assessment in moderate haemophilia.