C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Cerebral Venous Thrombosis: Clinical, Radiological, Biological, and Etiological Characteristics of a French Prospective Cohort (FPCCVT)-Comparison With ISCVT Cohort.

Introduction: Cerebral venous thrombosis (CVT) is a rare disease with highly variable clinical presentation and outcome. Etiological assessment may be negative. The clinical and radiological presentation and evolution can be highly variable. The mechanisms involved in this variability remain unknown. Objective: The aim of this multicenter French study registered on ClinicalTrials.gov (NCT02013635) was therefore to prospectively recruit a cohort of patients with cerebral venous thrombosis (FPCCVT) in order to study thrombin generation and clot degradation, and to evaluate their influence on clinical radiological characteristics. The first part of the study was to compare our cohort with a reference cohort. Methods: This prospective, multicenter, French study was conducted from July 2011 to September 2016. Consecutive patients (aged >15 years) referred to the stroke units of 21 French centers and who had a diagnosis of symptomatic CVT were included. All patients gave their written informed consent. The diagnosis of CVT had to be confirmed by imaging. Clinical, radiological, biological, and etiological characteristics were recorded at baseline, at acute phase, at 3 months and at last follow-up visit. Thrombophilia screening and the choice of treatment were performed by the attending physician. All data were compared with data from the International Study on CVT published by Ferro et al. Results: Two hundred thirty-one patients were included: 117 (50.6%) had isolated intracranial hypertension, 96 (41.5%) had focal syndrome. During hospitalization, 229 (99.1%) patients received anticoagulant treatment. Median length of hospital stay was 10 days. Five patients died during hospitalization (2.2%). At 3 months, 216 patients (97.0%) had follow-up with neurological data based on an outpatient visit. The mean duration of antithrombotic treatment was 9 months, and the mean time to last follow-up was 10.5 months. At the end of follow-up, eight patients had died, and 26 patients were lost to follow-up. At least one risk factor was identified in 200 patients. Conclusions: We demonstrated that the FPCCVT cohort had radiological, biological, and etiological characteristics similar to the historical ISCVT cohort. Nevertheless, the initial clinical presentation was less severe in our study probably due to an improvement in diagnostic methods between the two studies.

Risk Factors for Bleeding in Hospitalized at Risk Patients With an INR of 5 or More Treated With Vitamin K Antagonists.

Various predictive scores for vitamin K antagonist (VKA)-related bleeding have been developed and validated in outpatients and in patients treated for specific indications (when VKAs are used under optimal therapeutic conditions). However, there are few published data on the evaluation of bleeding risk factors in hospitalized, at-risk patients (with a high international normalized ratio [INR]) treated with VKAs. The objective of the present study was to identify the most relevant bleeding risk factors in 906 VKA-treated patients with an INR of 5 or more hospitalized in a French university medical center.Over a 2-year period, we screened all consecutive VKA-treated adults with a risk of major bleeding (defined as an INR ≥ 5 on admission). Demographic and clinical characteristics, medications, and bleeding characteristics were recorded prospectively.The overall incidence of bleeding was 26.6% (serious bleeding: 21.4%; fatal bleeding: 5.4%). An INR ≥ 8.5, a history of recent digestive tract lesions, trauma in the preceding 2 weeks, and known noncompliance were independent risk factors for bleeding and serious bleeding.Our present findings emphasize that VKAs should not be prescribed to patients with a high risk of bleeding (noncompliant patients and those with recent trauma or recent gastrointestinal lesions). It is essential to monitor the INR on a frequent basis and adjust oral anticoagulant treatment appropriately.

Aspirin non-responder status and early neurological deterioration: a prospective study.

OBJECTIVES: In acute ischemic stroke, early neurological deterioration (END) has a severe impact on patient outcome. We tested the hypothesis that initial biological aspirin non-responder status (ANRS) helps predict END. METHODS: A total of 85 patients with acute ischemic stroke on 160mg aspirin daily were prospectively included. END was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) ≥4 points in the first 72h after admission. Platelet responsiveness to aspirin was assessed using the PFA-100 system, and ANRS was defined as a collagen/epinephrine closure time <165ms. RESULTS: END was observed in 10 patients (11.8%). The presumed reasons for END were progressive stroke (40%), recurrent cerebral ischemia (30%), malignant middle cerebral artery infarction (20%) and secondary acute hydrocephalus (10%). Patients with END had a non-significant worse neurological status on the NIHSS at hospital admission (8.4 vs. 4.2; p=0.15). Initial impaired consciousness (30% vs. 3%), visual disturbance (60% vs. 23%) and ANRS (60% vs. 20%) were observed more frequently in patients with END. In multivariate analysis, impaired consciousness (OR: 17.3; 95% CI: 2.0-149.5; p=0.01) and ANRS (OR: 6.4; 95% CI: 1.4-29.6; p=0.017) were found to be independently associated with END. CONCLUSION: ANRS is common in acute ischemic stroke patients and is predictive of END. The clinical significance of these findings requires further evaluation in larger longitudinal studies.

Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study.

BACKGROUND: High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study. METHODS: The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty-four healthy subjects matched for age and sex formed the group control. RESULTS: Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p<0.001). Using previously reported cut off values (>150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009). CONCLUSION: Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.

Quality evaluation of the management of oral anticoagulation therapy (OAT): the awareness of treating physicians and the education of patients needs to be improved.

The adverse effects of oral anticoagulant therapy (OAT) are the main cause of hospitalization for drug accidents, and most of them could be avoided by more rigorous management. We conducted a prospective study based on the analysis of individuals under OAT recruited among the patients admitted to our hospital. The aim was to evaluate the legitimacy of OAT and the quality of its management by referring to general recommendations. Eighty-six patients were included. In 10, the disease justifying OAT was not included in the French recommendations. Contraindications to OAT were observed in 5 patients. Six drug associations were dangerous. The day of admission, the INR value was beyond the therapeutic range in 27 patients and under in 27 patients. Nine patients had been admitted to the hospital for an adverse effect of OAT (hemorrhage or thrombotic event). The risk of adverse effects was higher when the indications of OAT were outside the recommendations, when a contraindication to OAT existed, or when OAT had been prescribed beyond the necessary duration. A low number of patients knew their INR target, the risks of over- and under-anticoagulation, and the dangers of consuming certain drugs and foods. The overall risk linked to OAT would be diminished if the treatment was prescribed within the legitimate indications and the necessary duration, and taking greater account of the contraindications. The awareness of physicians prescribing OAT needs improvement. The lack of knowledge of the treatment by the patient him- or herself, which may be due to a lack of information or to a misunderstanding, should be counterbalanced by a reinforced education, even if it is time-consuming for the physician.

[Assessment of the quality of oral anticoagulation management in patients admitted to Amiens University Hospital]. / Evaluation à l'occasion de leur hospitalisation de la qualité de l'anticoagulation orale chez des patients traités par antivitamines K.

BACKGROUND: Excessive or insufficient anticoagulation therapy and its associated risks are of major concern in patients receiving oral anticoagulants. Such complications can be avoided by more rigorous management. OBJECTIVE: The aim of our study was to evaluate those patients receiving oral anticoagulant therapy on the day of hospitalisation among all patients admitted to the Amiens University Hospital during 14 days. METHODS: We evaluated the quality of management of the treatment in these patients, taking into account the international normalised ratio (INR), as well as important parameters such as the summary of the product characteristics (SPCs), drug interactions, and the level of knowledge of anticoagulant treatment by the patients themselves (questionnaire). RESULTS: Of the 2498 adult patients hospitalised, 86 patients (30 female and 56 male aged between 26 and 95 years [mean 70 years]) treated with oral anticoagulants were evaluated. At admission, seven cases of haemorrhage and two of thrombosis were registered. One drug-related death occurred and one patient had sequelae. In 17.5% of the cases, the prescription was not fully in agreement with the SPCs. This percentage increased to 67% for patients with adverse effects. In 41% of the patients, the INR was outside the therapeutic zone. The dosage regimen was too complex in 11% of cases. Six drug combinations were labelled as not recommended in the SPCs: four with aspirin <3 g/day and two with nonsteroidal anti-inflammatory drugs. The analysis of questionnaires showed that patients had insufficient knowledge of their treatment: only 16 of 66 knew the risks resulting from overdose or an insufficient dose of the anticoagulant drug, 25 of 66 knew that anticoagulation induced by the treatment can be influenced by food, 10 of 66 knew the therapeutic range of the INR appropriate for them, and 8 of 66 knew that intramuscular injections were prohibited. CONCLUSIONS: These data confirm that anticoagulant treatment needs to be more strictly controlled in order to avoid adverse effects. Risks are probably underestimated by physicians. Information given to patients seems insufficient or unsuitable (too complex).

[History of the therapeutic uses of the tinder polypore, Fomes fomentarius (L. : Fr]. / Histoire des utilisations thérapeutiques de l'amadouvier, Fomes fomentarius (L. :Fr.) Fr.

This paper presents the major therapeutic uses of Fomes fomentarius (L. : Fr.) Fr., tinder polypore. The context of this fungus is a wooly and soft material so called amadou (tinder). During the XVIII and XIXth centuries, the fungal material was used as haemostatic dressing and bandage to keep the temperature and compress parts of the body. It was also used as cautery for moxibustion and was reported in several traditional pharmacopoeias (Hungarian, Chinese, Indian).