Laura Franco

Major bleeding with vitamin K antagonists or direct oral anticoagulants in real-life

BACKGROUND Limited data are available on major bleeding (MB) occurring during treatment with vitamin K (VKAs) or direct oral anticoagulants (DOACs) outside clinical trials. METHODS Patients hospitalized for MB while on treatment with VKAs or DOACs were included in a multicenter study to compare clinical presentation, management and outcome of bleeding. The primary study outcome was death at 30days. RESULTS Between September 2013 and September 2015, 806 patients were included in the study, 76% on VKAs and 24% on DOACs. MB was an intracranial hemorrhage in 51% and 21% patients on VKAs or DOACs, respectively (Odds Ratio [OR] 3.79; 95% confidence interval [CI] 2.59-5.54) a gastrointestinal bleeding in 46% and 25% patients on DOACs and VKAs, respectively (OR 2.62; 95% CI 1.87-3.68). Death at 30days occurred in 130 patients (16%), 18% and 9% of VKA and DOAC patients (HR 1.95; 95% CI 1.19-3.22, p=0.008). The rate of death at 30days was similar in VKA and DOAC patients with intracranial hemorrhage (26% and 24%; HR 1.05, 95% CI 0.54-2.02) and gastrointestinal bleeding (11% and 7%; HR 1.46, 95% CI 0.57-3.74) and higher in VKA than DOAC patients with other MBs (10% and 3%; HR 3.42, 95% CI 0.78-15.03). CONCLUSIONS Admission for ICH is less frequent for DOAC patients compared with VKA patients. Admission for gastrointestinal MB is more frequent for DOAC as compared to VKA patients. Mortality seems lower in patients with MBs while on DOACs than VKAs but this finding varies across different types of MBs.

New oral anticoagulants for the treatment of venous thromboembolism

New oral anticoagulants, acting either as direct factor-Xa or thrombin inhibitors, have been evaluated for the acute and long-term treatment of venous thromboembolism (VTE). Dabigatran and rivaroxaban are as effective as conventional therapy (heparin/vitamin K antagonists) without safety concerns. Rivaroxaban allows a single-drug regimen even in patients with pulmonary embolism, while dabigatran requires 5-7 days of initial heparin treatment. The results of clinical trials with apixaban and edoxaban will become available in the coming months. Rivaroxaban, apixaban and dabigatran are more effective than placebo for the extended treatment of VTE. Apixaban is effective in both therapeutic and prophylactic doses. Considering both efficacy and bleeding complications, all these agents have a favorable net clinical benefit. Dabigatran is as effective and safe as warfarin for the extended treatment of VTE. It is conceivable that the new oral anticoagulants will become the standard therapy for VTE in the next years.

Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis

Essentials The optimal management of isolated distal deep vein thrombosis (IDDVT) is undefined. This meta‐analysis aimed to assess the clinical benefit of anticoagulation for IDDVT. Anticoagulation reduced the rate of pulmonary embolism without increasing major bleeding risk. Recurrent thromboembolism was less common with more than 6 weeks vs. 6 weeks of anticoagulation.

Purse-string closure versus conventional primary closure of wound following stoma reversal: Meta-analysis of randomized controlled trials

PURPOSE Surgical site infection (SSI) is one of the most frequent complications after stoma closure and the optimal skin closure technique is still not clear. The goal of this review was to compare outcomes with purse-string closure technique (PSC) versus conventional closure technique (CCT) for skin closure after stoma reversal. METHODS We performed a systematic review and meta-analysis of available randomized controlled trials (RCTs) to compare SSI rate within 30 days, operative time, hospital stay, incisional hernia and intestinal obstruction rates between PSC and CCT. RESULTS The pooled analysis of 5 studies showed a statically significant lower rate of SSI in favor of PSC compared to CCT (OR -0.24; 95% CI -0.32, - 0.15; p < 0.00001). No statistically significant differences were observed in the operative time (OR -0.05; 95% CI -3.95, 3.84; p = 0.98) and in the length of hospital stay (OR -0.20; 95% CI -0.76, 0.36; p = 0.48), between the two techniques. Additionally, two out of the five studies provided data on incisional hernia and intestinal obstruction and the pooled analysis revealed no statistically significant differences between PSC and CCT techniques: incisional hernia (OR 0.81, 95% CI 0.27-2.47; p = 0.71) and intestinal obstruction (OR 1.07, 95% CI 0.41-2.84; p = 0.88). CONCLUSIONS The analysis of 5 RCTs showed that SSI rate is statistically significant lower when PSC is performed, compared to CCT. Whereas, no significant differences were found between the two techniques with regards to operative time, length of hospital stay, incisional hernia and intestinal obstruction rates.

Treatment of venous thromboembolism in patients with cancer: What news from clinical trials?

About 15% of patients with cancer experience one or more episodes of venous thromboembolism (VTE) during the course of their disease. In patients with cancer, VTE has a substantial impact on the quality of life and care. Current guidelines recommend low-molecular-weight heparin (LMWH) as first choice therapy for long-term anticoagulation in cancer patients with VTE. However, there are several practical issues concerning the long-term use of these anticoagulants. In the last years, several direct oral anticoagulants (DOACs) have emerged as alternatives to heparins and vitamin K antagonists for the treatment of VTE, but data regarding both efficacy and safety of DOACs in the subgroup of patients with cancer treatments were limited. The results of two studies evaluating the clinical benefit of treatment of VTE with direct oral anticoagulants in patients with cancer have been recently presented. Several studies comparing DOACs with LMWH are currently ongoing.

Acute Pulmonary Embolism after Discharge: Duration of Therapy and Follow-up Testing

Abstract Pulmonary embolism (PE) is a frequent cause of death and serious disability with a risk extending far beyond the acute phase of the disease. Anticoagulant treatment reduces the risk for death and recurrent VTE after a first PE. The optimal duration of anticoagulation after a first episode of PE remains controversial and should be made on an individual basis, balancing the estimated risk for recurrence without anticoagulant treatment against bleeding risk under anticoagulation. Current recommendations on duration of anticoagulation are based on a 3% per year risk of major bleeding expected during long‐term warfarin treatment. Anticoagulant therapy should be discontinued after the initial 3 to 6 months in those patients who had the first episode in association with temporary risk factors. After 3 to 6 months of anticoagulant treatment, patients with a first unprovoked event and an estimated low risk for bleeding complications should be evaluated for indefinite treatment on an individualized basis. None of the clinical prediction models for recurrent VTE are able to actually drive duration of anticoagulation. If the favorable safety profile of direct oral anticoagulants from clinical trials would be confirmed in real‐life, extension of anticoagulation could be reconsidered in large proportions of patients after an unprovoked PE. The most feared late sequela of PE is chronic thromboembolic pulmonary hypertension. Although there has been progress in both the diagnosis and management of this disease in recent years, further data are needed to provide recommendations regarding long‐term follow‐up after PE.

Clinical management and outcome of major bleeding in patients on treatment with vitamin K antagonists.

BACKGROUND The optimal management of major bleeding associated with vitamin K antagonists remains unclear. OBJECTIVES The aim of the study was to assess the determinants of outcome of vitamin K antagonists-associated major bleeding and the outcome of bleeding in relation with the therapeutic management. METHODS Patients hospitalized for major bleeding while on vitamin K antagonists were included in a prospective, cohort study. Major bleeding was defined according to the criteria of the International Society of Thrombosis Haemostasis. The primary study outcome was death at 30days from major bleeding. RESULTS 544 patients were included in this study, of which 282 with intracranial hemorrhage. Prothrombin complex concentrates were used in 51% and in 23% of patients with intracranial hemorrhage or non-intracranial major bleeding, respectively (p<0.001); fresh frozen plasma was used in 7% and in 17% of patients with intracranial hemorrhage or non-intracranial major bleeding (p<0.001). Death at 30days occurred in 100 patients (18%), 72 patients with intracranial hemorrhage and 28 patients with non-intracranial major bleeding. Age over 85years, low Glasgow Coma Scale score and shock were independent predictors of death at 30days. Invasive procedures were associated with decreased risk of death. CONCLUSIONS Among the patients hospitalized for major bleeding while on vitamin K antagonists, the risk for death is substantial. The risk for death is associated with the clinical severity of major bleeding as assessed by the GCS score and by the presence of shock more than with the initial localization of major bleeding (ICH vs other sites).