Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials.

OBJECTIVE: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively). METHODS: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84. RESULTS: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25). CONCLUSIONS: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Increased blood viscosity and red blood cell aggregation in patients with COVID-19.

The aim of this study was to (1) analyze blood viscosity, red blood cell (RBC) deformability, and aggregation in hospitalized patients with Coronavirus disease 19 (COVID-19); (2) test the associations between impaired blood rheology and blood coagulation; and (3) test the associations between impaired blood rheology and several indicators of clinical severity. A total of 172 patients with COVID-19, hospitalized in COVID-unit of the Internal Medicine Department (Lyon, France) participated in this study between January and May 2021. Clinical parameters were collected for each patient. Routine hematological/biochemical parameters, blood viscosity, RBC deformability and aggregation, and RBC senescence markers were measured on the first day of hospitalization. A control group of 38 healthy individuals was constituted to compare the blood rheological and RBC profile. Rotational thromboelastography was performed in 76 patients to study clot formation dynamics. Our study demonstrated that patients with COVID-19 had increased blood viscosity despite lower hematocrit than healthy individuals, as well as increased RBC aggregation. In-vitro experiments demonstrated a strong contribution of plasma fibrinogen in this RBC hyper-aggregation. RBC aggregation correlated positively with clot firmness, negatively with clot formation time, and positively with the length of hospitalization. Patients with oxygen supplementation had higher RBC aggregation and blood viscosity than those without, and patients with pulmonary lesions had higher RBC aggregation and enhanced coagulation than those without. This study is the first to demonstrate blood hyper-viscosity and RBC hyper-aggregation in a large cohort of patients with COVID-19 and describe associations with enhanced coagulation and clinical outcomes.

The modification of the thrombin generation assay for the clinical assessment of hypercoagulability in patients receiving heparin therapy.

BACKGROUND: Heparin diminishes thrombin generation (TG) because it decreases the survival time of thrombin in plasma. Under heparin therapy, the TG curve therefore does not reflect the true hemostatic status of the patient. AIM: We investigated how far the in vitro addition of a heparin antagonist can restore the underlying TG capacity. MATERIALS & METHODS: Five different heparin antagonists were tested: polybrene, protamine sulfate, heparinase type 1, heparinase HEP-TEM, and (Z-GGR)2 -rhodamine (P2Rho). RESULTS AND CONCLUSION: Polybrene, P2Rho, and heparinase HEP-TEM effectively neutralized heparin at prophylactic and therapeutical doses of both low molecular weight and unfractionated heparin. The advantages and limits of each molecule and the most favorable combinations of TG-trigger and antagonist are discussed.

Highly sensitive serum cardiac troponin T and cardiovascular events in patients with systemic lupus erythematosus (TROPOPLUS study).

OBJECTIVE: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE. METHOD: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. RESULTS: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE. CONCLUSION: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.

Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence.

BACKGROUND: Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. METHODS: HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ < 200 ng/mL. RESULTS: The mean (± SD) HCQ levels were 469 ± 223 ng/mL in serum and 916 ± 449 ng/mL in whole blood. The mean ratio of serum/whole-blood HCQ levels was 0.53 ± 0.15. In the multivariate analysis, low whole-blood HCQ levels (P = 0.023), but not serum HCQ levels, were independently associated with active SLE. From the mean serum/whole-blood level ratio, a serum HCQ level of 106 ng/mL was extrapolated as the corresponding cut-off to identify non-adherent patients with a sensitivity of 0.87 (95% CI 0.76-0.94) and specificity of 0.89 (95% CI 0.72-0.98). All serum HCQ levels of patients with whole-blood HCQ below the detectable level (< 20 ng/mL) were also undetectable (< 20 ng/mL). CONCLUSIONS: These data suggest that whole blood is better than serum for assessing the pharmacokinetic/pharmacodynamic relation of HCQ. Our results support the use of serum HCQ levels to assess non-adherence when whole blood is unavailable.

Reversal of rivaroxaban anticoagulant effect by prothrombin complex concentrates: which dose is sufficient to restore normal thrombin generation?

Rivaroxaban has the most available data to support the use of prothrombin complex concentrates (PCC) as a reversal agent. However, PCC might increase the incidence of thrombotic events by shifting the haemostatic balance towards hypercoagulability. We assessed the in vitro efficacy and safety of three 4-factor PCCs for reversing rivaroxaban anticoagulant effect. Our in vitro finding indicates that 4-factor PCCs at the dose of 25 U.kg- 1 may be sufficient to reverse rivaroxaban anticoagulant effect.

Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis.

BACKGROUND: Thirty percent of Covid-19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis. Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies. Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies. OBJECTIVE: We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid-19 patients. PATIENTS AND METHODS: Forty-eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study. All patients received thromboprophylaxis. We measured fibrinolytic parameters (tissue plasminogen activator, PAI-1, thrombin activatable fibrinolysis inhibitor, alpha2 anti-plasmin, and tissue plasminogen activator-modified ROTEM device), thrombin generation, and other coagulation tests (D-dimer, fibrinogen, factor VIII, antithrombin). RESULTS AND CONCLUSIONS: We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI-1 levels. A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid-19 patients with thrombosis.

Anti-Domain I ß2-Glycoprotein I Antibodies and Activated Protein C Resistance Predict Thrombosis in Antiphospholipid Syndrome: TAC(I)T Study.

BACKGROUND: Antibodies binding to domain I of ß2-glycoprotein I (aDI) and activated protein C (APC) resistance are associated with an increased risk of thrombosis in cross-sectional studies. The objective of this study was to assess their predictive value for future thromboembolic events in patients with antiphospholipid antibodies (aPL) or antiphospholipid syndrome. METHODS: This prospective multicenter cohort study included consecutive patients with aPL or systemic lupus erythematosus. We followed 137 patients (43.5 ± 15.4 year old; 107 women) for a mean duration of 43.1 ± 20.7 months. RESULTS: We detected aDI IgG antibodies by ELISA in 21 patients. An APC sensitivity ratio (APCsr) was determined using a thrombin generation-based test. The APCsr was higher in patients with anti-domain I antibodies demonstrating APC resistance (0.75 ± 0.13 vs 0.48 ± 0.20, P < 0.0001). In univariate analysis, the hazard ratio (HR) for thrombosis over time was higher in patients with aDI IgG (3.31 [95% CI, 1.15-9.52]; P = 0.03) and patients with higher APC resistance (APCsr >95th percentile; HR, 6.07 [95% CI, 1.69-21.87]; P = 0.006). A sensitivity analysis showed an increased risk of higher aDI IgG levels up to HR 5.61 (95% CI, 1.93-16.31; P = 0.01). In multivariate analysis, aDI IgG (HR, 3.90 [95% CI, 1.33-11.46]; P = 0.01) and APC resistance (HR, 4.98 [95% CI, 1.36-18.28]; P = 0.02) remained significant predictors of thrombosis over time. CONCLUSIONS: Our study shows that novel tests for antibodies recognizing domain I of ß2-glycoprotein I and functional tests identifying APC resistance are significant predictors of thrombosis over time and may be useful for risk stratification.

Long-term efficacy of remission-maintenance regimens for ANCA-associated vasculitides.

OBJECTIVE: To compare long-term efficacy of remission-maintenance regimens in patients with newly diagnosed or relapsing antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. METHODS: The 28-month Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis trial compared rituximab with azathioprine to maintain remission in patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis or renal-limited ANCA-associated vasculitis. Thereafter, prospective patient follow-up lasted until month 60. The primary endpoint was the major-relapse rate at month 60. Relapse and serious adverse event-free survival were also assessed. RESULTS: Among the 115 enrolled patients, only one was lost to follow-up at month 60. For the azathioprine and rituximab groups, respectively, at month 60, the major relapse-free survival rates were 49.4% (95% CI 38.0% to 64.3%) and 71.9% (95% CI 61.2% to 84.6%) (p=0.003); minor and major relapse-free survival rates were 37.2% (95% CI 26.5% to 52.2%) and 57.9% (95% CI 46.4% to 72.2%) (p=0.012); overall survival rates were 93.0% (95% CI 86.7% to 99.9%) and 100% (p=0.045) and cumulative glucocorticoid use was comparable. Quality-adjusted time without symptoms and toxicity analysis showed that rituximab-treated patients had 12.6 months more without relapse or toxicity than those given azathioprine (p<0.001). Antiproteinase-3-ANCA positivity and azathioprine arm were independently associated with higher risk of relapse. HRs of positive ANCA to predict relapse increased over time. CONCLUSION: The rate of sustained remission for ANCA-associated vasculitis patients, following rituximab-based or azathioprine-based maintenance regimens, remained superior over 60 months with rituximab, with better overall survival. TRIAL REGISTRATION NUMBER: NCT00748644.

Efficacy of sildenafil on ischaemic digital ulcer healing in systemic sclerosis: the placebo-controlled SEDUCE study.

OBJECTIVE: To assess the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on digital ulcer (DU) healing in systemic sclerosis (SSc). METHODS: Randomised, placebo-controlled study in patients with SSc to assess the effect of sildenafil 20 mg or placebo, three times daily for 12 weeks, on ischaemic DU healing. The primary end point was the time to healing for each DU. Time to healing was compared between groups using Cox models for clustered data (two-sided tests, p=0.05). RESULTS: Intention-to-treat analysis involved 83 patients with a total of 192 DUs (89 in the sildenafil group and 103 in the placebo group). The HR for DU healing was 1.33 (0.88 to 2.00) (p=0.18) and 1.27 (0.85 to 1.89) (p=0.25) when adjusted for the number of DUs at entry, in favour of sildenafil. In the per protocol population, the HRs were 1.49 (0.98 to 2.28) (p=0.06) and 1.43 (0.93 to 2.19) p=0.10. The mean number of DUs per patient was lower in the sildenafil group compared with the placebo group at week (W) 8 (1.23±1.61 vs 1.79±2.40 p=0.04) and W12 (0.86±1.62 vs 1.51±2.68, p=0.01) resulting from a greater healing rate (p=0.01 at W8 and p=0.03 at W12). CONCLUSIONS: The primary end point was not reached in intention-to-treat, partly because of an unexpectedly high healing rate in the placebo group. We found a significant decrease in the number of DUs in favour of sildenafil compared with placebo at W8 and W12, confirming a sildenafil benefit. TRIAL REGISTRATION NUMBER: NCT01295736.

Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up.

OBJECTIVES: Growing evidence suggests that vitamin D plays a key role in the pathogenesis and progression of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent studies have found an association between lower serum 25-hydroxyvitamin D (25(OH)D) levels and higher SLE activity. We studied the relationship between 25(OH)D levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and we assessed for the first time the role of vitamin D in predicting SLE flare-ups. METHODS: Serum 25(OH)D levels were measured in 170 patients with SLE who were prospectively followed up for 6 months (Plaquenil LUpus Systemic study, ClinicalTrials.gov number NCT00413361). RESULTS: The mean SLEDAI score was 2.03±2.43 and 12.3% patients had active disease (SLEDAI ≥6). The mean 25(OH)D level was 20.6±9.8 ng/mL. Deficiency (25(OH)D <10 ng/mL) was observed in 27 (15.9%), insufficiency (10≤25(OH)D<30) in 112 (65.9%) and optimal vitamin D status (25(OH)D≥30) in 31 (18.2%) patients. In multivariate analysis, female gender (p=0.018), absence of defined antiphospholipid syndrome (p=0.002) and higher creatinine clearance (p=0.004) were predictive of lower 25(OH)D levels. In multivariate analysis, lower 25(OH)D levels were associated with high SLE activity (p=0.02). Relapse-free survival rate was not statistically different according to the vitamin D status during the 6-month follow-up (p=0.22). CONCLUSIONS: We found a low vitamin D status in the majority of patients with SLE, and a modest association between lower 25(OH)D levels and high disease activity. There was no association between baseline 25(OH)D levels and relapse-free survival rate.

Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study).

INTRODUCTION: Hydroxychloroquine (HCQ) is an important medication for treating systemic lupus erythematosus (SLE). Its blood concentration ([HCQ]) varies widely between patients and is a marker and predictor of SLE flares. This prospective randomised, double-blind, placebo-controlled, multicentre study sought to compare standard and adjusted HCQ dosing schedules that target [HCQ] ≥1000 ng/ml to reduce SLE flares. PATIENTS AND METHODS: [HCQ] was measured in 573 patients with SLE (stable disease and SELENA-SLEDAI≤12) treated with HCQ for at least 6 months. Patients with [HCQ] from 100 to 750 ng/ml were randomised to one of two treatment groups: no daily dose change (group 1) or increased HCQ dose to achieve the target [HCQ] (group 2). The primary end point was the number of patients with flares during 7 months of follow-up. RESULTS: Overall, mean [HCQ] was 918±451 ng/ml. Active SLE was less prevalent in patients with higher [HCQ]. A total of 171 patients were randomised and followed for 7 months. SLE flare rates were similar in the two groups (25% in group 1 vs 27.6% in group 2; p=0.7), but a significant spontaneous increase in [HCQ] in both groups between inclusion and randomisation strongly suggested improved treatment adherence. Patients at the therapeutic target throughout follow-up tended to have fewer flares than those with low [HCQ] (20.5% vs 35.1%, p=0.12). CONCLUSIONS: Although low [HCQ] is associated with higher SLE activity, adapting the HCQ dose did not reduce SLE flares over a 7-month follow-up.

Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features and long-term outcome: a case-control study of 8 patients.

Reactive hemophagocytic syndrome (RHS) is a rare, life-threatening, and little-known complication of rheumatic diseases. This disorder is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms. RHS may develop in patents who have lymphoma, organ transplantation, serious infection, and rheumatic diseases, most notably systemic lupus erythematosus and adult-onset Still disease (AOSD). Observations of specific cases of RHS in AOSD remain rare, and the significance of this syndrome during the course of AOSD remains unknown. We retrospectively studied 16 episodes of AOSD-associated RHS in 8 patients. To determine whether RHS is associated with a particular phenotype of AOSD, we conducted a case-control study from the cohort of AOSD patients seen during the same period. The estimated frequency of RHS in AOSD patients from our cohort was 15.3% (8/52). The median age at RHS diagnosis was 44.5 years. We collected clinical and laboratory data. RHS was the first manifestation of AOSD in 7 cases. The main symptoms were fever (n = 8), salmon rash (n = 6), arthralgia (n = 7), lymphadenopathy (n = 6), and shock (n = 4). Serum ferritin concentration was consistently elevated (>1000 microg/L in 8 cases), and the level of glycosylated ferritin was low in all cases (<5% in 7 cases, 15% in 1 case). Six patients presented with coagulopathy; hypertriglyceridemia was found in 6 cases. Admission to the intensive care unit was required in 4 cases. Treatment included corticosteroids (n = 8) and intravenous immunoglobulin (n = 6), cyclophosphamide in 2 cases, infliximab in the same 2 cases, and cyclosporine in 1 case. With a follow-up ranging from 2 to 15 years, the patients were in remission with prednisone plus methotrexate (n = 4), prednisone plus infliximab (n = 2), and low-dose prednisone alone (n = 2). We compared the 8 patients included in this study with 44 control patients with AOSD without RHS. Low haptoglobin levels, very high ferritin levels (>10,000 microg/L), and a normal or low neutrophil count seem to be predictive factors of the occurrence of RHS in AOSD.

2008 French national guidelines for the treatment of venous thromboembolism in patients with cancer: report from the working group.

Venous thromboembolism (VTE) is a major therapeutic issue in cancer patients. Advances in this field and heterogeneities in clinical practices prompted us to establish guidelines in the management of VTE in cancer patients according to the SOR (Standards, Options and Recommendations) methodology. A literature review of the studies published on this topic between 1999 and 2007 was performed. The guidelines were developed from the analysis of 38 out of 418 publications selected. They were peer-reviewed by 65 independent experts. The treatment of VTE in patients with cancer, including those with intracranial malignancies, should be based on low-molecular-weight heparins administered at therapeutic doses for at least 3 months. In the event of recurrent VTE, pulmonary embolism with hemodynamic failure or contra-indication to anticoagulant treatment, the indications and usages of vena cava filters and thrombolytic drugs should be the same as in non-cancer patients.

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study.

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63.98%) and 191 patients (66.8%) had a thrombophilia marker. Eighty nine (46.6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61.8% of patients with high risk of VTE. Among them, 37.7% were treated in the third trimester only and 24.1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0.35%) and two postpartum-related VTE (0.7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0.35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

[Recommendations for venous thromboembolic events treatment and central venous catheter thrombosis management in cancer patients]. / Traitement curatif de la maladie thromboembolique veineuse et prise en charge des thromboses veineuses sur cathéter chez les patients atteints de cancer Méthode SOR.

The "Standards, Options: Recommendations" (SOR) project has been undertaken by the French National Federation of Cancer Centers (FNCLCC) and is now part of the French National Cancer Institute. The project involves the development and updating of evidence-based Clinical Practice Guidelines (CPG) in oncology. In order to answer questions related to venous thromboembolic events (VTE) treatment and to central venous catheter thrombosis (CVCT) management in cancer patients, the SOR elaborated national guidelines, here presented in a short report. It results of a collaborative work with members from three learned societies (<< Société nationale française de médecine interne >> : SNFMI, << Société française de médecine vasculaire >> : SFMV and << Société française d'anesthésie-réanimation >> : SFAR).