[Translation into French and republication of: "Management of venous thromboembolic disease in patients with malignant brain tumours"]. / Traduction et republication de : « Prise en charge de la maladie thromboembolique veineuse chez les patients atteints de tumeurs cérébrales malignes ¼.

This article addresses the management of venous thromboembolism in patients with malignant brain tumours, including both primary and secondary (metastatic) tumours. The available data on patients on venous thromboembolism recurrence and bleeding risks in patients with brain tumours is limited, since these patients have been excluded from most randomised, interventional, head-to-head, clinical trials comparing low molecular weight heparins to vitamin K antagonists or to direct oral factor Xa inhibitors. More information is available from retrospective observational studies, which however were generally small, and carried a high risk of confounding. Their findings suggest that direct factor Xa inhibitor use is associated with lower rates of intracranial haemorrhage compared with low molecular weight heparins. Overall, the safety profile of direct oral factor Xa inhibitors when used to prevent venous thromboembolism recurrence in patients with either primary or secondary brain tumours appears to be favourable. The available data are in favour of using an anticoagulant at a full therapeutic dose in patients with primary and secondary brain tumours experiencing a venous thromboembolism, although they are not yet sufficiently robust to permit recommending a direct factor Xa inhibitor over low-molecular weight heparin.

Isolated distal deep vein thrombosis: What have we learnt from the OPTIMEV study?

The OPTIMEV (OPTimisation de l'Interrogatoire dans l'évaluation du risque throMbo-Embolique Veineux) study has provided some important and innovative information for the management of lower extremity isolated distal deep vein thrombosis (distal DVT). Indeed, if distal deep-vein thrombosis (DVT) therapeutic management is nowadays still debated, before the OPTIMEV study, the clinical relevance of these DVT itself was questioned. Via the publication of 6 articles, between 2009 and 2022, assessing risk factors, therapeutic management, and outcomes of 933 patients with distal DVT we were able to demonstrate that: - When distal deep veins are systematically screened for suspicion of DVT, distal DVT are the most frequent clinical presentation of the venous thromboembolic disease (VTE). This is also true in case of combined oral contraceptive related VTE. - Distal DVT share the same risk factors as proximal DVT and constitute two different clinical expressions of the same disease: the VTE disease. However, the weight of these risk factors differs: distal DVT are more often associated with transient risk factors whereas proximal DVT are more associated with permanent risk factors. - Deep calf vein and muscular DVT share the same risk factors, short and long-term prognoses. - In patients without history of cancer, risk of unknown cancer is similar in patients with a first distal or proximal DVT. - After 3years and once anticoagulation has been stopped, distal DVT recur twice less as proximal DVT and mainly as distal DVT; However, in cancer patients, prognosis of distal and proximal DVT appear similar in terms of death and VTE recurrence.

Evaluation of socio-economic insecurity in peripheral artery disease patients.

The social and economic environment has become a major determinant of cardiovascular health. The objective of our study was to assess socio-economic insecurity in patients with symptomatic PAD. The PRECAR study was a non-interventional prospective cohort study. Patients were recruited from the Vascular Medicine and Surgery Departments of Grenoble-Alpes University Hospital or during a consultation as part of the therapeutic education program "On the move! Better understanding and better living with arterial disease". The analysis of socio-economic and environmental data was based on the EPICES score (a reliable index used to measure individual deprivation) and INSEE parameters (level of education and socio-professional category). Cardiovascular risk factors were also recorded. 150 patients with symptomatic PAD were included between November 2017 and June 2018. 84% were men. In our population 54% (CI95% 45.7 - 62.1) were in a precarious situation compared to 40% (CI95% 39.8 - 40.2) in the general population, according to the EPICES score (P<0.001). Levels of education were low and patients with a baccalaureate or higher education degree were under-represented. Executives, intellectuals and intermediate professions were also under-represented in the PAD population. This data opens new perspectives on the social characterisation of patients that may contribute to improving the outcomes of patients with peripheral vascular disease.

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for the treatment of cancer-associated thrombosis (which agent for which patient).

Venous thromboembolism (VTE) is a common complication among patients with cancer, associated with significant higher rate of mortality and morbidity. Low-molecular-weight heparin (LMWH) as a single therapeutic is considered as the standard of care for the treatment of acute cancer-associated thrombosis for many years, showing a significant 40% reduction of recurrent VTE (RR: 0.58; 95% CI, 0.43 - 0.77) without a significant increase of major bleeding complications compared to VKA (RR: 1.09; 95% CI 0.55 - 2.12). Based on results analysis studies only including patients with proximal DVT or PE the risk of recurrent VTE was similar in the DOAC and the LMWH (RR 0.68; 95% CI, 0.39 - 1.17) groups, without significantively increasing the risk of either major bleeding (RR = 1.32; 95% CI 0.7 - 2.47) or CRNMB (RR 1.6; 95% 0.99 - 2.6). Compared with LMWH, the risk of major bleeding and clinically relevant-non major bleeding was higher, although non-significantly, with DOACs than with LMWH, underlying that DOACs should be avoided in patients at high risk of bleeding. The higher risk of bleeding reported in DOACs-treated patients appears related to an excess of upper GI bleeding. In addition to GI cancer, other high-risk features associated with bleeding complications are an urothelial cancer, drug-drug interactions and use of anticancer drugs associated with GI toxicity. Overall, DOACs are an effective treatment option, and safe in most cancer patients with acute VTE. Nonetheless, DOACs should be used with caution in cancer patients at high risk for bleeding due to cancer site and stage per se or to cancer treatments.

[Venous thromboembolic disease: questions and controversies. Teaching seminary in vascular medicine (November22, 2007)]. / Maladie thromboembolique veineuse : questions et controverses. Séminaire pédagogique du DESC de médecine vasculaire (22novembre2007).

Rapid advances has been made in the diagnosis and treatment of venous thromboembolic disease, but many questions or controversies remain. In this review, we present a progress report on various concepts still open to discussion. New epidemiologic data from the French epidemiology study, Optimev, are presented. Widespread use of multidetector CT scan for the diagnostic work-up of pulmonary embolism has had considerable impact on clinical practices. We discuss indications and use of the various imaging methods. The review ends with a report on constitutional or acquired thrombophilia, particularly cancer-associated venous thromboembolic disease, which remains a daily preoccupation with various approaches still under debate. This review was the topic of the French vascular medicine teaching seminary in November2007.

[Prolongation of anti vitamin K treatment for 18 months versus placebo after 6 months treatment of a first episode of ideopathic pulmonary embolism: a mutlicentre, randomised double blind trail. The PADIS-EP Trial]. / Prolongation d'un traitement par antivitamine K pendant dix-huit mois versus placebo au décours d'un premier épisode d'embolie pulmonaire idiopathique traité six mois: un essai randomisé multicentrique en double aveugle. Essai "PADIS-EP".

BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

[College of the French Vascular Medicine Teachers (CEMV) statement: Arterial Doppler waveforms analysis (simplified Saint-Bonnet classification)]. / Recommandations du Collège des enseignants de médecine vasculaire (CEMV) : analyse des flux artériels Doppler (classification de Saint-Bonnet simplifiée).

Lower extremity peripheral artery disease is a frequent disease. Arterial Doppler waveforms analysis is a key element in vascular medicine, especially to diagnose lower peripheral artery disease. Although Doppler waveforms are often used, descriptions are highly heterogeneous. This review presents the simplified Saint-Bonnet classification that is tought to vascular medicine residents in order to homogenize arterial flow description.

Characterization of endothelial-like cells derived from human mesenchymal stem cells.

BACKGROUND: Blood-derived endothelial progenitor cells (EPC) have been used to treat ischemic disease. However, the number of EPC that can be obtained from adult blood is limited. OBJECTIVE: To characterize endothelial-like cells obtained from human bone marrow and determine their ability to stimulate new blood vessel formation in vivo. METHODS: Mononuclear cells (MNC) were isolated from human bone marrow or umbilical cord blood and cultured in endothelial growth medium (EGM-2). Mesenchymal stem cells (MSC) were isolated from bone marrow and induced to differentiate into endothelial-like cells (MSCE), or adipocytes or osteocytes by growth in EGM-2, adipogenic or osteogenic medium. RESULTS: Cells obtained by culturing bone marrow MNC in EGM-2 formed cord- or tube-like structures when grown on Matrigel(TM) and expressed several endothelial marker proteins. However, cell morphology and the profile of endothelial marker protein expression were different from those of cord blood-derived EPC (cbEPC). Cells with a similar phenotype were obtained by differentiation of MSC into MSCE, which was accompanied by an increase of endothelial marker proteins and a diminished capacity to differentiate into adipocytes. Subcutaneous implantation of MSCE in collagen plugs in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice resulted in formation of functional blood vessels that had incorporated the MSCE. CONCLUSIONS: Our results show that MSCE and cbEPC are different cell types. The formation of functional blood vessels by MSCE, combined with high yields and a reduced capacity to differentiate into other cell types compared with MSC, makes these cells potentially useful for autologous therapy of ischemic disease.

Non-conform diagnostic management of pulmonary embolism suspected patients is responsible for a higher risk of thrombotic event occurrence.

The aim of this 3-month follow-up prospective pragmatic study was to evaluate the implementation of a pulmonary embolism (PE) diagnostic strategy in clinical practice. One thousand and one hundred thirty-four consecutive in- and outpatients with clinically suspected PE were enrolled into a sequential diagnostic algorithm in which vascular medical unit plays a pivotal role in advising physicians and suggesting the most appropriate tests according to the diagnostic algorithm. In this observational study, patients that followed the proposed work-up were attributed to a so-called "conform group". Patients in whom diagnostic work-up was not according to protocol were attributed to a "non-conform group". Nine hundred and ninety-seven patients (87.9%) had a conform work-up, and 137 patients a non-conform work-up according to the proposed diagnostic algorithm. The non-conform work-up directly increased in relation to the age of the referred patients. PE was ruled out in 907 (80%) patients of whom 787 (86.8%) were in the conform group. Of the 797 patients who did not receive anticoagulant drugs, follow-up was obtained in 792 (99.4%). Among these patients, the incidence of acute thromboembolic events during the 3-month follow-up period was different in the group of patients that had a conform work-up (1%, [95% CI, 0.5-2.1%]) from the non-conform group patients (4.5%, [95% CI, 2-10.2%]. Therefore patients from the non-conform group have an independent increased risk to develop a thromboembolic event during the follow-up, adjusted odds ratio 3.3 [1.1-10, 95% CI]. Therefore we demonstrated that a non-conform diagnostic management strategy is associated with a higher risk of thrombotic event occurrence.

Early antithrombotic treatment with warfarin oral suspension in severe neonatal protein C deficiency.

Neonatal severe protein C deficiency is a serious disease. There is no uniform approach for long-term preventive treatment of thrombotic events. We report the case of neonatal severe protein C deficiency treated with warfarin oral suspension. An international normalized ratio (INR) from 2.5 to 3.5 was expected. The INR was measured by home monitoring using the Coaguchek XS® (Roche Diagnostics, Mannheim, Germany) monitor. During 2years of warfarin treatment, there were only two minor episodes of purpuric access and no bleeding was reported. This case suggests that the early introduction of warfarin oral suspension, home-care monitoring, and parental education programs may be a beneficial treatment option for children with protein C deficiency.

Prevention and treatment of cancer-associated thrombosis in France: A national survey among vascular disease and supportive care specialists.

BACKGROUND/AIM: Long-term use of low-molecular-weight heparins (LMWH) for the treatment of cancer-associated thrombosis (CAT) has been well-established. Conversely, the use of thromboprophylaxis in patients with cancer remains controversial in the absence of homogeneous guidelines. Our aim was to assess the awareness of treatment guidelines and the management of patients with CAT in daily clinical practice. METHODS: A national survey based on an open questionnaire developed by a panel of health professionals including specialists in vascular medicine, oncology, supportive care and pharmacy, was proposed on line to 2104 specialists experts in the management of CAT with the objective to collect at least 400 answers. Clinical practice assessment included the treatment of lung adenocarcinoma-associated thrombosis, the use of thromboprophylaxis and factors influencing the management of patients with CAT. RESULTS: A total of 401 questionnaires were completed by specialists of vascular medicine (68%), oncology (12%) and other (20%). LMWH was the preferred option for over 90% of the participants for the treatment of recent overt proximal pulmonary embolism or deep-vein thrombosis. Up to 70% of the participants considered treatment duration for 6 months and more than 12 months in case of active malignancy. Patient management in the setting of incidental VTE and thromboprophylaxis were heterogeneous in the absence of clear guidance while VTE risk scores would be used by only 14% of participants. CONCLUSION: Patients with CAT are properly managed based on clear and consistent guidelines. Patient care is heterogeneous regarding treatment duration beyond 6 months and thromboprophylaxis while VTE risk scores are misused. Identification of referent health care professionals for CAT management and more clear guidelines are required.

Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study.

Essentials Clinical significance of cancer-related isolated distal deep vein thrombosis (iDDVT) is unknown. We studied patients with iDDVT, with and without cancer, and proximal DVT with cancer. Cancer-related iDDVT patients have a much poorer prognosis than iDDVT patients without cancer. Cancer-related iDDVT patients have a similar prognosis to cancer-related proximal DVT patients. SUMMARY: Background Isolated distal deep vein thrombosis (iDDVT) (infra-popliteal DVT without pulmonary embolism [PE]) is a frequent event and, in the absence of cancer, is usually considered to be a minor form of venous thromboembolism (VTE). However, the clinical significance of cancer-related iDDVT is unknown. Methods Using data from the observational, prospective multicenter OPTIMEV cohort, we compared, at 3 years, the incidences of death, VTE recurrence and major bleeding in patients with cancer-related iDDVT with those in cancer patients with isolated proximal DVT (matched 1:1 on age and sex) and patients with iDDVT without cancer (matched 1:2 on age and sex). Results As compared with patients with cancer-related isolated proximal DVT (n = 92), those with cancer-related iDDVT (n = 92) had a similar risk of death (40.8% per patient-year (PY) vs. 38.3% per PY; aHR = 1.0, 95% CI[0.7-1.4]) and of major bleeding (3.8% per PY vs. 3.6% per PY, aCHR = 0.9 [0.3-3.2]) and a higher risk of VTE recurrence (5.4% per PY vs. 11.5% per PY; aCHR = 1.8 [0.7-4.5]). As compared with patients with iDDVT without cancer (n = 184), those with cancer-related iDDVT had a nine times higher risk of death (3.5% per PY vs. 38.3% per PY; aHR = 9.3 [5.5-15.9]), a higher risk of major bleeding (1.8% per PY vs. 3.6% per PY; aCHR = 2.0 [0.6-6.1]) and a higher risk of VTE recurrence (5.0% per PY vs. 11.5% per PY; aCHR = 2.0 [1.0-3.7]). The results remained similar in the subgroup of patients without history of VTE. Conclusion Patients with cancer-related iDDVT seem to have a prognosis that is similar to that of patients with cancer-related isolated proximal DVT and a dramatically poorer prognosis than patients with iDDVT without cancer. This underlines the high clinical significance of cancer-related iDDVT and the need for additional studies.

Long-term risk of venous thromboembolism recurrence after isolated superficial vein thrombosis.

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.

[Clinical use of bedside cerebral microdialysis: a review]. / Utilisation clinique du monitorage biochimique cérébral par microdialyse: revue de la littérature.

OBJECTIVE: To review the current data on clinical bedside use of cerebral microdialysis. DATA SOURCE: Search through Medline database of articles in French and English (keywords: microdialysis, cerebral ischaemia, head trauma, subarachnoid haemorrhage, clinical study). STUDY SELECTION: All clinical articles published between 1995 and 2005, including original papers and some case reports. DATA SYNTHESIS: Microdialysis after occlusive stroke has shown elevated levels of glutamate and lactate. When space-occupying oedema develops, biochemistry abnormalities occur first, before ICP increases. Bedside microdialysis appears to be a sensitive and earlier indicator of space occupying oedema. Most Accurate markers to monitor ischaemia induced by vasospasm are glutamate and lactate/pyruvate ratio. These markers are earlier than clinical abnormalities or pressure measurements (sensibility 82%, specificity 89%). In the field of head trauma, the same compounds were utilised. The level of these compounds correlates with outcome in a different manner whether the area studied is close to a concussion or not. Most of biochemical events are linked to global cerebral ischaemia. We can observe some abnormalities limited to the pericontusional area, which are not detected by the global monitoring. Microdialysis appears a useful tool to investigate disease mechanisms but cannot be recommended for a widespread use after head trauma. CONCLUSION: Bedside cerebral microdialysis allows clinical decisions in the setting of subarachnoid haemorrhage and ischaemic stroke. It represents a valuable tool to investigate head trauma pathophysiology.

[Management of deep-vein thrombosis: A 2015 update]. / Prise en charge de la thrombose veineuse profonde en 2015.

Deep vein thrombosis (DVT) is a frequent and multifactor disease, with two major complications, post thrombotic syndrome and pulmonary embolism. Both transient (surgery, plaster immobilization, bed rest/hospitalization) and chronic/persistent (age, cancer, clinical or biological thrombophilia…) risk factors modulate treatment duration. Diagnostic management relies on clinical evaluations, probability followed by laboratory tests or imaging. So far, compression ultrasound is the diagnostic test of choice to make a positive diagnosis of DVT. Anticoagulants at therapeutic dose for at least 3 months constitute the cornerstones of proximal (i.e. involving popliteal or more proximal veins) DVT therapeutic management. The arrival of new oral anticoagulants should optimize ambulatory management of DVT.

[Management of pulmonary embolism: A 2015 update]. / Prise en charge de l'embolie pulmonaire en 2015.

Pulmonary embolism (PE) is a frequent, serious and multifactorial disease, the incidence of which increases with advanced age. In the absence of pathognomonic clinical signs or symptoms, diagnostic management lies in the evaluation of clinical pre-test probability followed by a laboratory or an imaging test. So far, multidetector computed tomography angiography is the diagnostic test of choice to make a positive diagnosis of PE. Anticoagulants at therapeutic dose for at least 3 months constitute the cornerstones of PE therapeutic management. Duration of anticoagulant treatment is modulated according to the presence of transient (surgery, plaster immobilization, bed rest/hospitalization) and chronic/persistent (age, cancer, clinical or biological thrombophilia…) risk factors of PE. Thrombolysis is usually prescribed only for cases of severe PE with arterial hypotension. Arrival of new oral anticoagulants, which have recently been shown to be as effective and as safe as vitamin K antagonist, should simplify and ease ambulatory management of PE and favor more prolonged treatments with anticoagulant for cases of unprovoked PE or PE provoked by a chronic/persistent risk factor.

Low incidence of cancer after venous thromboembolism: An update from the French OPTIMEV Cohort.

BACKGROUND: Recent studies have shown lower rates of cancer following venous thromboembolism (VTE) than previously described. OBJECTIVES: To reassess the risk of cancer in patients with clinical symptoms of VTE with or without confirmed VTE. PATIENTS: We used data from OPTIMEV, a French prospective multicenter observational study of patients presenting to hospital and community vascular medicine specialists with suspected VTE. Patients with confirmed VTE (1565) and matched controls without VTE (1847) were followed for 3 years (2006-2009). The main outcome was occurrence of cancer at 3 years, and death was a censoring event. RESULTS: A total of 5.0% [4.0-6.3] of patients with VTE and 3.8% [3.0-4.9] without VTE developed cancer during follow-up. The adjusted hazard ratio (HR) was 1.2 [0.9-1.8] for patients with confirmed VTE (P=0.22). The overall standardized incidence ratio (SIR) was 1.4 [1.1-1.6] for our population, VTE+ and VTE-, compared with the general population, statistically significant (P<0.05). CONCLUSIONS: We found a lower occurrence of cancer after VTE than previously described, with no significant difference between patients whether VTE was confirmed or not. Our results (low incidence and no difference between patients VTE+ or VTE-) provide no argument in favor of an extensive screening for cancer in case of VTE.