Antipsychotics: a real or confounding risk factor for venous thromboembolism?

In a meta-analysis of case-control studies, Zhang et al. (2011) found an increased risk of venous thromboembolic events (VTE) in patients exposed to antipsychotics (OR=2.39 [1.71-3.35]). Our updated meta-analysis including the 2 available cohort studies, recognized as a more relevant type of observational study, showed a weaker, but still strong association (OR=1.84 [1.39; 2.44]). In view of the lack of data on the confirmed risk factors for VTE in existing studies, prospective studies including adjustment for these risk factors are warranted to confirm this association and to assess the benefit/risk ratio of antipsychotics in high-risk patients.

Clinical presentation and outcome of venous thromboembolism in COPD.

Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous thromboembolism (VTE), but neither the clinical presentation nor the outcome of VTE in COPD patients is well known. The clinical presentation of VTE, namely pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3 months (death, recurrent VTE or bleeding) were compared between 2,984 COPD patients and 25,936 non-COPD patients included in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. This ongoing international, multi-centre registry includes patients with proven symptomatic PE or DVT. PE was the more frequent VTE presentation in COPD patients (n = 1,761, 59%). PE presentation was more significantly associated with COPD patients than non-COPD patients (OR 1.64, 95% CI 1.49-1.80). During the 3-month follow-up, mortality (10.8% versus 7.6%), minor bleeding (4.5% versus 2.3%) or first VTE recurrences as PE (1.5% versus 1.1%) were significantly higher in COPD patients than in non-COPD patients. PE was the most common cause of death. COPD patients presented more frequently with PE than DVT. It may explain the worse prognosis of COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE compared with non-COPD patients. Further therapeutic options are needed.

Value of a planned compression ultrasonography after an isolated superficial vein thrombosis: results from a prospective multicentre study.

OBJECTIVES: To assess the efficiency of a systematically planned compression ultrasonography (SP-CUS) to detect venous thrombotic complications (VTCs) in patients with symptomatic isolated superficial vein thrombosis (SVT). DESIGN: Post hoc analysis of a prospective, multicentre, cohort study (POST). PATIENTS: As many as 537 patients with CUS-confirmed isolated SVT undergoing an SP-CUS 8-15 days after the initial CUS. OUTCOMES: Asymptomatic VTC (extension or recurrence of SVT, deep-vein thrombosis (DVT) of the lower limbs) diagnosed by the SP-CUS and symptomatic thromboembolic complications (VTC and pulmonary embolism (PE)) up to 3 months. RESULTS: VTC was suspected before or on the day of the SP-CUS in 18 patients (3.0%). Among the 519 asymptomatic patients (97%) undergoing SP-CUS, this revealed asymptomatic VTC in 12 patients (2.3%; 4 DVT, 4 SVT recurrences, 4 SVT extensions), none of whom subsequently experienced symptomatic thromboembolic events up to 3 months. Among the 507 patients with a normal SP-CUS, 29 (5.7%) presented symptomatic thromboembolic events during follow-up: 2 PE, 7 DVT, 9 SVT recurrences and 11 SVT extensions. CONCLUSIONS: In this study, the SP-CUS detected a few asymptomatic VTC, but failed to identify patients at risk of thromboembolic events during follow-up. Use of an SP-CUS was therefore neither efficient nor cost effective.

Tranexamic acid in hip fracture surgery: a randomized controlled trial.

BACKGROUND: Hip fracture surgery may be associated with substantial blood loss. This study was designed to assess the efficacy and safety of the use of tranexamic acid in hip fracture surgery for the reduction of erythrocyte transfusion. METHODS: The study pertains to a randomized double-blind study with blinded adjudication of outcomes. Patients requiring surgery for an isolated hip fracture of less than 48 h received saline or tranexamic acid 15 mg kg(-1) given at skin incision and 3 h later. Primary efficacy outcome was erythrocyte transfusion from surgery up to day 8. Transfusion was administered according to a standardized protocol (Hb<9 g dl(-1)). Safety criterion was a composite of symptomatic and asymptomatic vascular events up to 6 weeks. RESULTS: Fifty-seven patients were randomized to tranexamic acid and 53 to placebo. The rate of erythrocyte transfusion was 42% with tranexamic acid and 60% with placebo (P=0.06). Preoperative haemoglobin value, age, and type of surgery were risk factors for erythrocyte transfusion independent of treatment group. The probability of vascular events at 6 weeks was 16% in the tranexamic acid group and 6% in the placebo group (P=0.10). A meta-analysis combining this study with previous trials showed that tranexamic acid significantly reduced erythrocyte transfusion in hip fracture surgery although efficacy was lower than that observed in hip or knee arthroplasty. CONCLUSIONS: In hip fracture surgery, tranexamic acid reduces erythrocyte transfusion but may promote a hypercoagulable state. Thus, further evaluation of safety is required before recommending the off-label use of tranexamic acid.

Comparison of the clinical history of symptomatic isolated distal deep-vein thrombosis vs. proximal deep vein thrombosis in 11 086 patients.

BACKGROUND: The clinical significance of symptomatic isolated distal deep vein thrombosis (DVT) is uncertain. Consequently, this leads to important disparities in its management. OBJECTIVE: To examine the clinical history of isolated distal DVT and to compare it with that of proximal DVT. METHODS: Using data from the international, prospective, RIETE registry on patients with confirmed symptomatic venous thromboembolism (VTE), we compared the risk factors and 3-month outcome in patients with isolated distal DVT vs. proximal DVT. RESULTS: Eleven thousand and eighty-six patients with symptomatic DVT, but without pulmonary embolism, were included between 2001 and 2008; 1921 (17.3%) exhibited isolated distal DVT. Anticoagulant treatment was received by 89.1% (1680/1885) of isolated distal DVT and 91.8% (7911/8613) of proximal DVT patients for the entire follow-up period. Isolated distal DVTs were more associated with transient risk factors (i.e. recent travel, hospitalization, recent surgery), whereas proximal DVTs were more associated with chronic states (i.e. > or =75 years or with active cancer). At 3 months, major bleeding rate was lower in patients with isolated distal DVT (1.0% vs. 2.2%, P < 0.01), whereas VTE recurrence rate was equivalent (2.0% vs. 2.7%, P = 0.07). The mortality rate was lower in patients with isolated distal DVT (2.7% vs. 7.5%; P < 0.001); this was mainly due to a lower rate of non-VTE-related deaths (2.2% vs. 6.3%; P < 0.001). Active cancer was the main predictive factor of death in patients with isolated distal DVT. CONCLUSIONS: Proximal and isolated distal DVT patients differ in terms of risk factors and clinical outcomes, suggesting different populations. In the short term, the life expectancy of patients with isolated distal DVT depended chiefly on their cancer status.

Serum and ascitic procalcitonin levels in cirrhotic patients with spontaneous bacterial peritonitis: diagnostic value and relationship to pro-inflammatory cytokines.

OBJECTIVE: To assess the potential role of procalcitonin and pro-inflammatory cytokines, TNF-alpha, and IL-6, in the diagnosis of spontaneous bacterial peritonitis (SBP). DESIGN: Prospective study. SETTING: The emergency unit of a teaching hospital. PATIENTS: We included 21 patients with SBP and 40 patients with sterile ascitic fluid. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the diagnosis of SBP, the best markers were serum levels of procalcitonin with a cut-off value of 0.75 ng/ml, a sensitivity of 95%, a specificity of 98%, and ascitic fluid levels of IL-6 with a cut-off value of 5,000 ng/ml, a sensitivity of 100%, and a specificity of 88%. C-reactive protein and serum polymorphonuclear count have low sensitivity/specificity at 62/92% and 57/90%, respectively. From 21 patients with SBP, ascitic fluid to serum ratio of TNF-alpha and IL-6 was greater than to 2 in all cases with a mean at 6.2 +/- 6.5 and 34 +/- 31, respectively. By contrast, this ratio for procalcitonin was less than 1 in all cases with a mean at 0.31 +/- 0.25. We found no correlation between procalcitonin levels and cytokine levels in either ascitic fluid or serum. CONCLUSIONS: Serum procalcitonin level may become a useful marker for the diagnosis of SBP in cirrhotic patients. The low ratio of ascitic fluid to serum procalcitonin supports the hypothesis that procalcitonin is not produced intraperitoneally.