Blood coagulation is a highly specialized process that is required to prevent blood loss following vascular damage. Central to the formation of a blood clot are the blood coagulation proteins... Show moreBlood coagulation is a highly specialized process that is required to prevent blood loss following vascular damage. Central to the formation of a blood clot are the blood coagulation proteins factor V and factor X. Aside from preventing blood loss, the coagulation system can also be exploited to gain selective advantages. The procoagulant venom of the Australian Elapid snakes comprises a powerful prothrombin-activating enzyme complex consisting of FV- and FX-like proteins that are specifically expressed in the venom gland. These coagulation proteins have evolved into potent toxins due to some remarkable gain-of-function adaptations that enable this prothrombinase-like complex to initiate coagulation in an uncontrolled manner. In this thesis, we focus on the unique evolutionary adaptations of the P. textilis venom derived proteins v-ptFV and v-ptFX. By using biochemical approaches, we assess the structure-function relationships of several uniquely modified structural elements Show less
Background and objective: Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and... Show moreBackground and objective: Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and region. We analyzed gender-specific antithrombotic treatment patterns in Spain and rest of Western Europe (rWE) in patients with NVAF. Methods: GLORIA-AF (Phase III) is a global, prospective, observational study which enrolled newly diagnosed NVAF patients with CHA(2)DS(2)-VAScs >= 1 (2014-2016). Analyses were performed comparing antithrombotic treatments by gender in Spain and rWE. Results: This analysis included 1163 and 7972 patients from Spain and rWE, respectively. Stroke risk was higher in women than men in both Spain and rWE. While in rWE, bleeding risk and antithrombotic treatment pattern were similar between genders, in Spain bleeding risk in women was lower and more females compared to men received OACs (95.0% versus 92.4%, d= -0.1078, respectively). Fewer Spanish patients received direct oral anticoagulants (DOACs) (women 32.1%, men 25.3%) than vitaminK-antagonists (VKAs) (women 63.0%, men 67.1%) vs. rWE patients. In Spain women received more DOACs compared to men (56.0% versus 44.0%). Conclusions: OAC rates were higher in Spain as compared to rWE. More women received OACs in Spain, while in rWE no difference by gender was observed. DOACs in rWE are the most prescribed OAC while in Spain, due to prescription barriers, its use remains low for both genders and VKAs are preferred. Spanish women received more DOACs compared to men. (C) 2021 The Authors. Published by Elsevier Espana, S.L.U. Show less
Nederpelt, C.; Naar, L.; Meier, K.; Wijck, S. van; Krijnen, P.; Velmahos, G.; ... ; Schipper, I. 2022
Introduction Emergency physicians and trauma surgeons are increasingly confronted with pre-injury direct oral anticoagulants (DOACs). The objective of this study was to assess if pre-injury DOACs,... Show moreIntroduction Emergency physicians and trauma surgeons are increasingly confronted with pre-injury direct oral anticoagulants (DOACs). The objective of this study was to assess if pre-injury DOACs, compared to vitamin K antagonists (VKA), or no oral anticoagulants is independently associated with differences in treatment, mortality and inpatient rehabilitation requirement. Methods We performed a review of the prospectively maintained institutional trauma registry at an urban academic level 1 trauma center. We included all geriatric patients (aged >= 65 years) with tICH after a fall, admitted between January 2011 and December 2018. Multivariable logistic regression analysis controlling for demographics, comorbidities, vital signs, and tICH types were performed to identify the association between pre-injury anticoagulants and reversal agent use, neurosurgical interventions, inhospital mortality, 3-day mortality, and discharge to inpatient rehabilitation. Results A total of 1453 tICH patients were included (52 DOAC, 376 VKA, 1025 control). DOAC use was independently associated with lower odds of receiving specific reversal agents [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.15-0.54] than VKA patients. DOAC use was independently associated with requiring neurosurgical intervention (OR 3.14, 95% CI 1.36-7.28). VKA use, but not DOAC use, was independently associated with inhospital mortality, or discharge to hospice care (OR 1.62, 95% CI 1.15-2.27) compared to controls. VKA use was independently associated with higher odds of discharge to inpatient rehabilitation (OR 1.41, 95% CI 1.06-1.87) compared to controls. Conclusion Despite the higher neurosurgical intervention rates, patients with pre-injury DOAC use were associated with comparable rates of mortality and discharge to inpatient rehabilitation as patients without anticoagulation exposure. Future research should focus on risk assessment and stratification of DOAC-exposed trauma patients. Show less
Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We... Show moreAims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients.Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA(2)DS(2)-VASc score of >= 2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA(2)DS(2)-VASc score >= 2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs.Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence. Show less
Aims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We... Show moreAims Persistence with direct oral anticoagulants (DOACs) has become a concern in non-valvular atrial fibrillation (NVAF) patients, but whether this affects prognosis is rarely studied. We investigated the persistence with oral anticoagulants (OACs) and its association with prognosis among a nationwide cohort of NVAF patients.Methods and results DOAC-naive NVAF patients who started to use DOACs for ischaemic stroke prevention between 2013 and 2018 were included using Dutch national statistics. Persistence with OACs was determined based on the presence of a 100-day gap between the last prescription and the end of study period. In 93 048 patients, 75.7% had a baseline CHA(2)DS(2)-VASc score of >= 2. The cumulative incidence of persistence with OACs was 88.1% [95% confidence interval (CI) 87.9-88.3%], 82.6% (95% CI 82.3-82.9%), 77.7% (95% CI 77.3-78.1%), and 72.0% (95% CI 71.5-72.5%) at 1, 2, 3, and 4 years after receiving DOACs, respectively. Baseline characteristics associated with better persistence with OACs included female sex, age range 65-74 years, permanent atrial fibrillation, previous exposure to vitamin K antagonists, stroke history (including transient ischaemic attack), and a CHA(2)DS(2)-VASc score >= 2. Non-persistence with OACs was associated with an increased risk of the composite outcome of ischaemic stroke and ischaemic stroke-related death [adjusted hazard ratio (aHR) 1.79, 95% CI 1.49-2.15] and ischaemic stroke (aHR 1.58, 95% CI 1.29-1.93) compared with being persistent with OACs.Conclusion At least a quarter of NVAF patients were non-persistent with OACs within 4 years, which was associated with poor efficacy of ischaemic stroke prevention. The identified baseline characteristics may help identify patients at risk of non-persistence. Show less
Background: In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty.Aim: We explored the results of an international... Show moreBackground: In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty.Aim: We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians.Methods and results: A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to similar to 60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively.Conclusion: This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF. Show less
The studies described in this thesis aim to improve both the diagnostic strategy in patients with suspected pulmonary embolism as well as the therapeutic management in patients with proven acute... Show moreThe studies described in this thesis aim to improve both the diagnostic strategy in patients with suspected pulmonary embolism as well as the therapeutic management in patients with proven acute pulmonary embolism. Show less
