Een ischemische beroerte als presentatie van een occulte maligniteit: typisch beeld op een MRI van de hersenen

Author(s):  
H. ENGELS ◽  
M. LEMMERLING ◽  
J. DE BLEECKER

Stroke as the first manifestation of an occult malignancy: typical pattern on a diffusion-weighted MRI An 89-year-old woman was admitted to the emergency department with temporary loss of coordination in her right arm. Diffusion-weighted imaging revealed the ‘three territory sign’ (TTS): multiple high-signal intensities in the territories of both the anterior and posterior circulations. Although a cardioembolic source is often suggested as the cause of multiple ischemic lesions, TTS is frequently seen in patients with a concomitant malignancy. When further investigated, the patient was diagnosed with a pancreatic carcinoma. The ischemic stroke was considered the first manifestation of the carcinoma, as conventional causes were excluded. Patients with a malignancy have an increased risk of an ischemic stroke. A potential explanation for this phenomenon is cancer-associated hypercoagulability. The treatment of cancer-associated hypercoagulability remains a challenge for clinicians. By analogy with the therapy for venous thromboembolic disorders in cancer patients, low-molecular-weight heparins (LMWH) could also be used safely and effectively for cancer-associated ischemic stroke. In different studies, variable results are observed with direct oral anticoagulants (DOACs) in the treatment of cancer-associated ischemic stroke. Despite the strong theoretical considerations, no clear benefit has been demonstrated for the use of anticoagulant versus antiplatelet therapy in this population. Further prospective research is needed.

Author(s):  
Karlo Huenerbein ◽  
Parvis Sadjadian ◽  
Tatjana Becker ◽  
Vera Kolatzki ◽  
Eva Deventer ◽  
...  

AbstractIn patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), arterial or venous thromboembolic events (ATE/VTE) are a major burden. In order to control these complications, vitamin K antagonists (VKA) are widely used. There is no robust evidence supporting the use of direct oral anticoagulants (DOAC) in MPN patients. We therefore compared the efficacy and safety of both anticoagulants in 71 cases from a cohort of 782 MPN patients. Seventy-one of 782 MPN patients (9.1%) had ATE/VTE with nine ATE (12.7%) and 62 VTE (87.3%). Forty-five of 71 ATE/VTE (63.4%) were treated with VKA and 26 (36.6%) with DOAC. The duration of anticoagulation therapy (p = 0.984), the number of patients receiving additional aspirin (p = 1.0), and the proportion of patients receiving cytoreductive therapy (p = 0.807) did not differ significantly between the VKA and DOAC groups. During anticoagulation therapy, significantly more relapses occurred under VKA (n = 16) compared to DOAC treatment (n = 0, p = 0.0003). However, during the entire observation period of median 3.2 years (0.1–20.4), ATE/VTE relapse-free survival (p = 0.2) did not differ significantly between the two anticoagulants. For all bleeding events (p = 0.516) or major bleeding (p = 1.0), no significant differences were observed between VKA and DOAC. In our experience, the use of DOAC was as effective and safe as VKA, possibly even potentially beneficial with a lower number of recurrences and no increased risk for bleedings. However, further and larger studies are required before DOAC can be routinely used in MPN patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji Yun Lee ◽  
Il-Young Oh ◽  
Ju-Hyeon Lee ◽  
Seok Kim ◽  
Jihoon Cho ◽  
...  

AbstractPolypharmacy is common in patients with atrial fibrillation (AF), making these patients vulnerable to the occurrence of potential drug-drug interactions (DDIs). We assessed the risk of ischemic stroke and major bleeding in the context of concomitant treatment with potential DDIs in patients with AF prescribed direct oral anticoagulants (DOACs). Using the common data model (CDM) based on an electronic health record (EHR) database, we included new users of DOACs from among patients treated for AF between January 2014 and December 2017 (n = 1938). The median age was 72 years, and 61.8% of the patients were males, with 28.2% of the patients having a CHA2DS2-VASc score in category 0–1, 49.4% in category 2–3, and 22.4% in category ≥ 4. The CHA2DS2-VASc score was significantly associated with ischemic stroke occurrence and hospitalization for major bleeding. Multiple logistic regression analysis showed that increased risk of ischemic stroke and hospitalization for major bleeding was associated with the number of DDIs regardless of comorbidities: ≥ 2 DDIs was associated with ischemic stroke (OR = 18.68; 95% CI, 6.22–55.27, P < 0.001) and hospitalization for major bleeding (OR = 5.01; 95% CI, 1.11–16.62, P < 0.001). DDIs can cause reduced antithrombotic efficacy or increased risk of bleeding in AF patients prescribed DOACs.


Author(s):  
Е.В. Ройтман ◽  
Т.В. Вавилова ◽  
С.М. Маркин ◽  
П.Ф. Кравцов ◽  
К.В. Мазайшвили

Введение. Поступление вируса SARS-CoV-2 в организм человека сопровождается развитием COVID-19-ассоциированной коагулопатии, часто реализующейся в различных тромботических осложнениях. Актуальные клинические рекомендации описывают основные подходы к лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО), однако реализация их не всегда представляется возможной. В реальной практике встречается значительное количество отклонений и нарушений, в том числе носящих системный характер, связанных как с ограниченностью представлений клиницистов о патогенетических аспектах развития инфекционного процесса, так и с избыточным желанием предотвратить отдельные из них. Цель исследования: изучение состояния реальной клинической практики в области лечения и профилактики развития тромботических осложнений у пациентов c новой коронавирусной инфекцией COVID-19 (НКИ COVID-19). Материалы и методы. В основе работы лежит анонимный опрос 223 врачей-специалистов, занимающихся лечением пациентов с хроническими и острыми заболеваниями сосудов. В опросник включено 18 вопросов, описывающих отношение врачей к проблеме в целом, а также касающихся выбора тактики лечения, применения антикоагулянтных препаратов и методов контроля системы гемостаза. Результаты. Подавляющее большинство участников опроса информированы и озадачены увеличением риска тромботических осложнений при НКИ COVID-19. При этом приоритетной целью антикоагулянтной терапии (АКТ) в острой фазе заболевания участники назвали лечение COVID-19-ассоциированной коагулопатии, а в стадии реконвалесценции — профилактику ВТЭО. Максимальную степень доверия при назначении АКТ имеют низкомолекулярные гепарины. Прямые оральные антикоагулянты, несмотря на отсутствие качественных рандомизированных исследований, подтверждающих их эффективность, большая часть врачей использует на амбулаторном этапе. Вызывает озабоченность значительный разброс вариантов и невысокий процент корректных ответов в вопросах, посвященных лабораторному контролю за системой гемостаза при АКТ. Заключение. Выполненный нами анализ свидетельствует о существенном расхождении реального применения антикоагулянтных препаратов у пациентов с НКИ COVID-19 с действующими клиническими рекомендациями. Кроме того, полученные результаты свидетельствуют о необходимости повышения уровня образованности практикующих специалистов в вопросах свертывания крови. Background. The SARS-CoV-2 virus invasion lead to COVID-19-associated coagulopathy accompanied with increased incidence of thrombotic complications. Current clinical guidelines give the main approaches to the treatment and prevention of them; however their implementation is not always possible in practice. In fact, there are a lot of violations including with a systemic genesis and associated either with the low understanding of infectious process pathogenesis aspects by clinicians or with their excessive desire to prevent coagulation disturbances. the revealing of real clinical practice conditions in the treatment and prevention of thrombotic complications in patients with coronavirus infection COVID-19. Materials/Methods. We provided an anonymous poll for 223 experts treating patients with chronic and acute vascular diseases. The questionnaire included 18 questions to identify as the experts attitude to this challenge as a whole as well as to their choice of treatment tactics, and anticoagulant drugs, and methods of laboratory monitoring of blood coagulation. Results. Most participants know the increased risk of thrombotic complications in COVID-19 and they are puzzled by it The treatment of COVID-19-associated coagulopathy is considered as the priority goal of anticoagulant therapy in the acute phase of COVID-19 whereas the prevention of venous thromboembolic complications is noted as main goal in convalescences. Low molecular weight heparins have gotten the highest confidence in the administration among anticoagulants. In turn, the most of experts use direct oral anticoagulants in outpatients even despite no confirmation is for DOAC’s effectiveness from randomized trials in this time. Besides it was revealed wide spread of opinions and low count of correct responses about laboratory control of the hemostatic system and anticoagulants. Conclusion. The analysis showed a serious inconsistency between the real anticoagulants administration in patients with COVID-19 and the recommendations of clinical guidelines. This circumstance obviates the need to raise educational level of physicians and surgeons in the field of blood coagulation.


2021 ◽  
Vol 30 (1) ◽  
pp. 16-23
Author(s):  
S. Moiseev

Over the last decade, the number of people aged 80 years or over in Russia increased by 41% up to 5.7 mln. At least 10% of these individuals develop atrial fibrillation (AF). Treatment of rhythm disorders in the very elderly patients is challenging due to the high occurrence of comorbidities, including cognitive dysfunction, changes in the pharmacokinetics of drugs as a result of reduced kidney function, increased risk of interaction of drugs. The very elderly patients with AF have a higher risk of ischemic stroke and other cardiovasculat outcomes, including myocardial infarction, and should be treated with oral anticoagulants. The results of randomized controlled trials and prospective and retrospective observational studies suggest that in patients aged 80 years or older with non-valvular AF direct oral anticoagulants (DOAC) are at least as effective as vitamin K antagonists for prevention of ischemic stroke and are associated with a lower risk of intracerebral haemorrhage. The use of DOAC (once daily rivaroxaban in particular) impoves compliance to anticoagulation in the very elderly patients with non-valvular AF.


2021 ◽  
Vol 80 (5) ◽  
pp. 598-604
Author(s):  
Cindy G Boer ◽  
Ingrid Szilagyi ◽  
N Long Nguyen ◽  
Tuhina Neogi ◽  
Ingrid Meulenbelt ◽  
...  

ObjectivesVitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP.MethodsWe investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association.ResultsAcenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94–3.20), both for knee (OR=2.34, 95% CI=1.67–3.22) and hip OA (OR=2.74, 95% CI=1.82–4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69–6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78–1.33).ConclusionsThese findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.


TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e417-e426
Author(s):  
Carline J. van den Dries ◽  
Sander van Doorn ◽  
Patrick Souverein ◽  
Romin Pajouheshnia ◽  
Karel G.M. Moons ◽  
...  

Abstract Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use (p-value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed (p-value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.


Gut ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 1805-1812 ◽  
Author(s):  
Naoyoshi Nagata ◽  
Hideo Yasunaga ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
Kazuhiro Watanabe ◽  
...  

ObjectiveTo compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures.DesignUsing the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups.ResultsIn the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk.ConclusionThe risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.


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