[Human immunodeficiency virus and venous thromboembolism: Role of direct oral anticoagulants]. / Modalités du traitement de la maladie veineuse thromboembolique du patient VIH par les anticoagulants oraux directs.

Nowadays, thanks to highly active antiretroviral therapy (HAART), human immunodeficiency virus (HIV) infection is transforming into a chronic disease. The life expectancy of people living with HIV (PWH) has increased, as well as their risk of developing several co-morbidities, in particular cardiovascular diseases. In addition, the incidence of venous thromboembolism (VTE) is increased in PWH with a 2 to 10 times higher incidence when compared to the general population. Over the last decade, direct oral anticoagulants (DOACs) have been widely used in the treatment and prevention of VTE and non-valvular atrial fibrillation. DOACs are characterized by a rapid onset of activity, a predictable response and a relatively wide therapeutic window. Nevertheless, drug interactions exist between HAART and DOACs, exposing PWH to a theoretically increased bleeding or thrombotic risk. DOACs are substrates of the transport protein P-glycoprotein and/or of isoforms of cytochromes P450 pathway, which can be affected by some antiretroviral drugs. Limited guidelines are available to assist physicians with the complexity of those drug-drug interactions. The aim of this paper is to provide an updated review on the evidence of the high risk of VTE in PWH and the place of DOAC therapy in this population.

Subarachnoid-pleural fistula: To drain or not to drain.

Subarachnoid-pleural fistula (SPF) is a rare complication of spine surgery with a transthoracic approach. The outcome of such an injury is affected by not only the pulmonary status due to the pleural effusion but also the neurological one, secondary to the intracranial hypotension. After reviewing the few published cases of SPF, the journey to diagnosis seams heterogenous and the management plan non-uniform. We report the case of a 48-year old women who underwent a right transthoracic discectomy that was complicated by an SPF. The diagnosis, although suspected perioperatively, was established with the gathering of an abundant post-operative pleural effusion, a subdural hematoma on head Computerized Tomography after drainage and Cerebro-Spinal Fluid markers present in the pleural fluid. The defect was effectively corrected with a radiological procedure. We compare our clinical and paraclinical findings and management plans to those reported in the few other published cases of SPF.

Performance of the age-adjusted cut-off for D-dimer in patients with cancer and suspected pulmonary embolism.

BACKGROUND: Cancer patients frequently present with suspected pulmonary embolism (PE). The D-dimer (DD) test is less useful in excluding PE in cancer patients due to the lower specificity. In the general population, the age-adjusted cutoff for DD combined with a clinical decision rule (CDR) improved specificity in the diagnosis of PE. OBJECTIVES: To evaluate the safety and efficacy of the age-adjusted cutoff (defined as age∗10µg/L in patients >50years) combined with a CDR for the exclusion of PE in cancer patients. METHODS: We conducted a prospective study to evaluate the age-adjusted cutoff in patients with suspected PE. Here we report a post-hoc analysis on the performance of the age-adjusted cutoff in patients with and without cancer. The primary outcome was the rate of venous thromboembolic events (VTE) during three-month follow-up. RESULTS: Of 3324 patients with suspected PE, 429 (12.9%) patients had cancer. The prevalence of PE was 25.2% in cancer patients and 18% in patients without cancer (p<0.001). Among cancer patients with an unlikely CDR, 9.9% had a DD <500µg/L as compared with 19.7% using the age-adjusted cutoff. In patients without cancer, these rates were 30.1% and 41.9%. The proportion of cancer patients in whom PE could be excluded by CDR and DD doubled from 6.3% to 12.6%. No VTE occurred during three-month follow-up (failure rate 0.0% (95% CI 0.0-6.9%)). CONCLUSION: Compared with the conventional cutoff, the age-adjusted D-dimer cutoff doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and DD without imaging.

PO-29 - Age-adjusted D-dimer cutoff level increases the number of cancer patients in who pulmonary embolism can be safely excluded without CT-PA imaging: The ADJUST-PE cancer substudy.

INTRODUCTION: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an age-adjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. AIM: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age×10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. MATERIALS AND METHODS: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an age-adjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. RESULTS: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 µg/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month follow-up, thus the failure rate was 0.0% (95% CI 0.0-6.9%). CONCLUSIONS: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.

Risk of recurrent venous thromboembolism and major hemorrhage in cancer-associated incidental pulmonary embolism among treated and untreated patients: a pooled analysis of 926 patients.

UNLABELLED: ESSENTIALS: We performed a pooled analysis of 926 patients with cancer-associated incidental pulmonary embolism (IPE). Vitamin K antagonists (VKA) are associated with a higher risk of major hemorrhage. Recurrence risk is comparable after subsegmental and more proximally localized IPE. Our results support low molecular weight heparins over VKA and similar management of subsegmental IPE. BACKGROUND: Incidental pulmonary embolism (IPE) is defined as pulmonary embolism (PE) diagnosed on computed tomography scanning not performed for suspected PE. IPE has been estimated to occur in 3.1% of all cancer patients and is a growing challenge for clinicians and patients. Nevertheless, knowledge about the treatment and prognosis of cancer-associated IPE is scarce. We aimed to provide the best available evidence on IPE management. METHODS: Incidence rates of symptomatic recurrent venous thromboembolism (VTE), major hemorrhage, and mortality during 6-month follow-up were pooled using individual patient data from studies identified by a systematic literature search. Subgroup analyses based on cancer stage, thrombus localization, and management were performed. RESULTS: In 926 cancer patients with IPE from 11 cohorts, weighted pooled 6-month risks of recurrent VTE, major hemorrhage and mortality were 5.8% (95% confidence interval [CI] 3.7-8.3%), 4.7% (95% CI 3.0-6.8%), and 37% (95% CI 28-47%). VTE recurrence risk was comparable under low molecular weight heparins (LMWH) and vitamin K antagonists (VKAs) (6.2% vs. 6.4%; hazard ratio [HR] 0.9; 95% CI 0.3-3.1), while 12% in untreated patients (HR 2.6; 95% CI 0.91-7.3). Risk of major hemorrhage was higher under VKAs than under LMWH (13% vs. 3.9%; HR 3.9; 95% CI 1.6-10). VTE recurrence risk was comparable in patients with an subsegmental IPE and those with a more proximally localized IPE (HR 1.1; 95% CI 0.50-2.4). CONCLUSION: These results support the current recommendation to anticoagulate cancer-associated IPE with LMWH and argue against different management of subsegmental IPE.

Risk factors and clinical outcome of unsuspected pulmonary embolism in cancer patients: a case-control study.

BACKGROUND: Little is known about the risk factors and outcome of unsuspected pulmonary embolism (UPE) in cancer patients. OBJECTIVES: To assess the risk factors and outcome of UPE in cancer patients. METHODS: The charts of 66 patients diagnosed with UPE were reviewed. Two control groups were selected: 132 cancer patients without pulmonary embolism (PE) and 65 cancer patients with clinically suspected PE. Variables associated with UPE were identified by multivariable analysis. Six-month survival and recurrent venous thromboembolism were compared by use of Cox proportional analysis. RESULTS: Twenty-seven (40.9%) patients with UPE had symptoms suggesting PE. Adenocarcinoma (odds ratio [OR] 4.45; 95% confidence interval [CI] 1.98-9.97), advanced age (OR 1.18; 95% CI 1.02-1.38), recent chemotherapy (OR 4.62; 95% CI 2.26-9.44), performance status > 2 (OR 7.31; 95% CI 1.90-28.15) and previous venous thromboembolism (OR 4.47; 95% CI 1.16-17.13) were associated with UPE. When adjusted for tumor stage and performance status, 6-month mortality did not differ between patients with UPE and patients without PE (hazard ratio 1.40; 95% CI 0.53-3.66; P = 0.50). Patients with UPE were more likely to have central venous catheters and chemotherapy and less likely to have proximal clots than patients with clinically suspected PE. Recurrent venous thromboembolism occurred in 6.1% and 7.7% of patients with UPE and symptomatic PE, respectively. CONCLUSION: UPE is not associated with an increased risk of death. Patients with clinically suspected PE and those with UPE have similar risks of recurrent venous thromboembolism.