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Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Introduction: Little is known about the clinical characteristics of women at increased risk for abnormal uterine bleeding (UB) during anticoagulation for venous thromboembolism (VTE). Methods: We used the RIETE registry to identify the baseline characteristics of women developing abnormal UB during anticoagulation. We used logistic regression analysis to identify independent predictors for abnormal UB. Then, we built a prognostic score to identify at-risk women. Results: From March 2001 through October 2022, there were 54,372 women with VTE. During anticoagulation (median, 181 days), 318 (0.6%) developed abnormal UB (major bleeding = 88, clinically relevant non-major (CRNM) = 230). On multivariable analysis, women aged 70 kg, with uterine cancer, recent UB, anemia, estrogen-related VTE, or receiving rivaroxaban or apixaban were at increased risk for abnormal UB. Using the prognostic score, 42,273 women (78%) were at low-risk, 8,828 (16%) intermediate-, and 3,271 (6.1%) at high-risk for abnormal UB. Their rates of abnormal UB were: 0.28 (95%CI: 0.23–0.35), 1.32 (95%CI: 1.07–1.61) and 7.12 (95%CI: 5.98–8.41) bleeds per 100 patient-years, respectively. The c-statistic was 0.80 (95%CI: 0.77–0.83). The rates of major UB were: 0.06 (95%CI: 0.04–0.09), 0.43 (95%CI: 0.30–0.60) and 1.85 (95%CI: 1.31–2.53) per 100 patient-years, respectively (c-statistic: 0.84; 95%CI: 0.80–0.89). The rates of CRNM uterine bleeding were: 0.21 (95%CI: 0.17–0.26), 0.85 (95%CI: 0.65–1.08), and 5.02 (95%CI: 4.09–6.10) bleeds per 100 patient-years, respectively (c-statistic: 0.78; 95%CI: 0.75–0.82). Conclusions: Using 7 variables easily available at admission, we built a prognostic score that reliably identified women with VTE at increased risk for abnormal UB during anticoagulation.

Background: The use of low-molecular-weight heparin (LMWH) for long-term therapy of venous thromboembolism (VTE) in patients without cancer has not been consistently evaluated. Methods: We used the data in the RIETE registry to compare the 3-month outcomes (VTE recurrences, major bleeding or death) in non-cancer patients with VTE, according to long-term therapy with LMWH or vitamin K antagonists (VKAs). Results: As of March 2018, 14,582 non-cancer patients with VTE had received initial therapy with LMWH and then switched to VKAs, while 9151 were prescribed LMWH for initial and long-term therapy. Overall, 11,494 had initially presented with pulmonary embolism (PE) and 12,239 with isolated deep vein thrombosis (DVT). Among 11,494 patients initially presenting with PE, 84 had VTE recurrences, 204 major bleeding and 406 died. Among 12,239 patients with isolated DVT, 133 developed VTE recurrences, 137 bled and 289 died. On propensity score analysis, PE patients on long-term LMWH therapy were at increased risk for PE recurrences (OR: 3.30; 95%CI: 1.67–6.48), major bleeding (OR: 1.68; 95%CI: 1.21–2.32) or death (OR: 3.16; 95%CI: 2.43–4.09) compared with those receiving VKAs. In patients with DVT, those on long-term LMWH also were at increased risk for PE recurrences (OR: 2.31; 95%CI: 1.13–4.73), major bleeding (OR 2.28; 95%CI: 1.51–3.44) or death (OR: 2.32; 95%CI: 1.54–3.51). Conclusions: In the RIETE non-cancer patients with VTE, long-term therapy with VKAs was associated with a lower risk for recurrences, major bleeding or death.

Background: Chronic immobility is prevalent, especially as people age. However, little is known about venous thromboembolism (VTE) outcomes in this population., Objective: To compare the presentation, treatment, and outcomes in chronically immobile (>8 weeks) patients older vs. younger than 75 who presented with VTE., Design: An observational international registry of patients with VTE., Participants: Patients with acute VTE from the "Registro Informatizado Enfermedad TromboEmbolica" (RIETE) registry who were chronically immobile., Main Measures: Baseline characteristics, presenting signs and symptoms, treatment and outcomes including major bleeding, recurrent VTE, and mortality., Key Results: Among 4612 immobile patients (mean age 75.7 years, 34% male), 2127 (46%) presented with pulmonary embolism (PE). Patients >75 years presented more often with dyspnea (44% vs. 38%) or altered mental status (23% vs. 8.1%) and less often with chest pain (13% vs. 18%). The median duration of anticoagulation was shorter in older compared with younger patients [126 vs. 169 days]. During the first 90 days of anticoagulation, major bleeding (4.0% vs. 2.2%), PE-related death (2.5% vs. 1.1%), and bleeding-related death (0.78% vs. 0.26%) occurred more frequently among older patients. In 3550 patients who received anticoagulation beyond 90 days, older patients had more major bleeding [4.23 vs. 2.21 events per 100 patient years]. After anticoagulation discontinuation, recurrent VTE and major bleeding occurred in 11.8 and 9.25 and 1.49 and 0.69 events per 100 patient years, respectively, both in similar rates in both groups. In multivariable analysis, after stopping anticoagulation, VTE recurrence was inversely associated with long-term facility residence [OR 0.51 (0.28-0.92)], anemia [OR 0.63 (0.42-0.95)], and anticoagulation duration < 90 days [OR 0.38 (0.27-0.54)]., Conclusions: Chronically immobilized patients older than 75 years presenting with VTE experience a high rate of adverse events including major bleeding and recurrent VTE. When considering treatment beyond 90 days, we should account for bleeding, recurrence risk, and associated mortality., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Purpose: Antithrombin (AT) deficiency is a well-known inherited risk factor for venous thromboembolism (VTE). However, F V Leiden and F II20210a mutations have drawn much more attention in the recent years. Therefore, we have decided to analyze the frequency of antithrombin deficiency in different cohorts of patients and tried to formulate indications for its testing., Results: Antithrombin deficiency was found in 4% of patients with recurrent VTE ≤ 50 years of age with, in 1% of patients with splanchnic vein thrombosis and in 2% of cases associated with combined oral contraceptives (COC) use or pregnancy. In patients with central venous thrombosis, antithrombin deficiency was not found., Recommendation: We consider antithrombin testing useful in patients with thrombosis occuring up to 45 years of age without any risk factors. Namely, females with VTE in pregnancy and puerperium should be tested as well as females with thrombosis on COC, if VTE occurred within the first year of their use., Conclusion: In spite of degressive interest in thrombophilia work up, we still consider antithrombin testing useful in defined clinical situations.

Background: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2., Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes., Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls., Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.

Objective: To address the association between psychiatric disorders and short-term outcomes after acute symptomatic pulmonary embolism (PE)., Methods: We identified adults with PE enrolled in the RIETE registry between December 1, 2013, and January 31, 2019. Using multinomial regression, we assessed the association between a history of psychiatric disorders and the outcomes of all-cause mortality, PE-related mortality, and venous thromboembolism recurrence and bleeding rates through 30 days after initiation of treatment. We also examined the impact of depression on all-cause and PE-specific mortality., Results: Among 13,120 patients diagnosed with acute PE, 16.1% (2115) had psychiatric disorders and 4.2% died within the first 30-days of follow-up. Patients with psychiatric disorders had increased odds for all-cause (adjusted odds ratio [OR] 1.50; 95% CI, 1.21 to 1.86; P < 0.001) and PE-related mortality (adjusted OR 1.64; 95% CI, 1.09 to 2.48; P = 0.02) compared to those without psychiatric disorders. Multinomial logistic regression showed a non-significant trend toward lower risk of recurrences for patients with psychiatric disorders (adjusted OR 0.49; 95% CI, 0.21 to 1.15; P = 0.10). Psychiatric disorders were not significantly associated with increased odds for major bleeds during follow-up (adjusted OR 1.09; 95% CI, 0.85 to 1.40; P = 0.49). Results were consistent in a sensitivity analysis that only considered patients with a diagnosis of depression., Conclusions: In patients with acute PE, history of psychiatric disorders might predict all-cause and PE-related death in the ensuing month after diagnosis., Competing Interests: Declaration of competing interest Dr. Bikdeli reports that he has been a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters. The current study is the idea of the investigators and has not been performed at the request of a third party., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background:  The influence (if any) of the use of psychotropic drugs on outcome in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated., Methods:  We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the risk for VTE recurrences, major bleeding, or death during the course of anticoagulant therapy, according to the use of psychotropics at baseline., Results:  Among 49,007 patients with VTE enrolled from February 2009 to September 2019, total 5,230 (11%) were using psychotropics at baseline: antidepressants 3,273 (6.7%), antipsychotics 1,588 (3.2%), and anticholinesterases 369 (0.7%). During the course of anticoagulation, 1,259 patients developed VTE recurrences, 1,231 bled, and 3,988 died (fatal pulmonary embolism 269 and fatal bleeding 187). On multivariable analysis, patients using psychotropics at baseline had a similar risk for VTE recurrences (adjusted hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.58-1.12), a nonsignificantly higher risk for major bleeding (adjusted HR: 1.15; 95% CI: 0.97-1.35), and a higher risk for intracranial bleeding (adjusted HR: 1.83; 95% CI: 1.32-2.53) or death (adjusted HR: 1.44; 95% CI: 1.32-1.57) compared with those not using psychotropics. When separately analyzed, the highest risk for intracranial bleeding was found in patients using antidepressants (adjusted HR: 1.60; 95% CI: 1.08-2.37) or antipsychotics (adjusted HR: 2.02; 95% CI: 1.17-3.49) but not in those on anticholinesterases (adjusted HR: 1.69; 95% CI: 0.62-4.60)., Conclusion:  During the course anticoagulation for VTE, patients using psychotropics at baseline were at increased risk for intracranial bleeding., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Primary retroperitoneal localization of non-Hodgkin's lymphoma is rare but should be considered, even if the circumstances surrounding its emergence point to other direction. We present a case of an appearance of periaortic infiltration after successful endovascular treatment which turned out to be of malignant origin.

Purpose: Retrospective evaluation of 12-year experience with endovascular management of acute mesenteric ischemia (AMI) due to embolic occlusion of the superior mesenteric artery (SMA)., Materials and Methods: From 2003 to 2014, we analysed the in-hospital mortality of 37 patients with acute mesenteric embolism who underwent primary endovascular therapy with subsequent on-demand laparotomy. Transcatheter embolus aspiration was used in all 37 patients (19 women, 18 men, median age 76 years) with embolic occlusion of the SMA. Adjunctive local thrombolysis (n = 2) and stenting (n = 2) were also utilised., Results: We achieved complete recanalization of the SMA stem in 91.9 %. One patient was successfully treated by surgical embolectomy due to a failed endovascular approach. Subsequent exploratory laparotomy was performed in 73.0 % (n = 27), and necrotic bowel resection in 40.5 %. The total in-hospital mortality was 27.0 %., Conclusion: Primary endovascular therapy for acute embolic SMA occlusion with on-demand laparotomy is a recommended algorithm used in our centre to treat SMA occlusion. This combined approach for the treatment of AMI is associated with in-hospital mortality rate of 27.0 %.

Background: No studies have identified which patients with upper-extremity deep vein thrombosis (DVT) are at low risk for adverse events within the first week of therapy., Methods: We used data from Registro Informatizado de la Enfermedad TromboEmbólica to explore in patients with upper-extremity DVT a prognostic score that correctly identified patients with lower limb DVT at low risk for pulmonary embolism, major bleeding, or death within the first week., Results: As of December 2014, 1135 outpatients with upper-extremity DVT were recruited. Of these, 515 (45%) were treated at home. During the first week, three patients (0.26%) experienced pulmonary embolism, two (0.18%) had major bleeding, and four (0.35%) died. We assigned 1 point to patients with chronic heart failure, creatinine clearance levels 30-60 mL min(-1) , recent bleeding, abnormal platelet count, recent immobility, or cancer without metastases; 2 points to those with metastatic cancer; and 3 points to those with creatinine clearance levels < 30 mL min(-1) . Overall, 759 (67%) patients scored ≤ 1 point and were considered to be at low risk. The rate of the composite outcome within the first week was 0.26% (95% confidence interval [CI] 0.004-0.87) in patients at low risk and 1.86% (95% CI 0.81-3.68) in the remaining patients. C-statistics was 0.73 (95% CI 0.57-0.88). Net reclassification improvement was 22%, and integrated discrimination improvement was 0.0055., Conclusions: Using six easily available variables, we identified outpatients with upper-extremity DVT at low risk for adverse events within the first week. These data may help to safely treat more patients at home., (© 2015 International Society on Thrombosis and Haemostasis.)

Objective: The aim of this study was to determine the efficacy of establishing a Post Caesarean Acute Pain Service., Design: Retrospective observational study., Setting: University Hospital Brno., Methods: We evaluated all patients undergoing delivery via Caesarean Section under anaesthesia in the periods 10/2009 - 9/2010 and 11/2010 - 10/2011. During the postoperative period at predefined times, we measured the Visual Analogue Scale, Additional Analgesic Requests, blood pressure, pulse rate and recorded any complications. We compared the Visual Analogue Scale Score and number of Additional Analgesic Requests in two groups of women, 212 patients before and 195 patients after the establishment of an Acute Pain Service in the first 72 hours after Caesarean Section., Results: There was a statistically significant difference in Visual Analogue Scale Score between the groups (p<0.05). The number of Additional Analgesic Requests 24-72 hours after Caesarean Section decreased below one requirement per 24 hours. The most effective analgesic method after Caesarean Section during the first 24 hours postoperatively was epidural analgesia. There was no statistically significant difference 24-72 hours after Caesarean Section between the methods of analgesia used., Conclusion: In conclusion, implementation of a Post Caesarean Acute Pain Service led to decrease in Visual Analogue Scale Score postoperatively., Keywords: Acute Pain Service, postoperative analgesia, Caesarean Section, non-opioid analgesia, opioid analgesia, epidural analgesia.

Background: The prognostic value of D-dimer testing in patients with acute pulmonary embolism (PE) has not been thoroughly studied., Methods: We used the RIETE Registry data to assess the 90-day prognostic value of increased IL Test D-dimer levels at baseline in patients with PE, according to the presence or absence of cancer., Results: As of May 2013, 3,283 patients with acute PE underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without cancer, those with D-dimer levels in the highest quartile had a higher rate of fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with levels in the lowest quartiles. Among 695 patients with cancer, those with levels in the highest quartile had a similar rate of fatal PE or fatal bleeding but higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer patients with D-dimer levels in the highest quartile had an increased risk for fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95% CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with patients with levels in the lowest quartiles., Conclusions: Non-cancer patients with acute PE and IL Test D-dimer levels in the highest quartile had an independently higher risk for fatal PE, fatal bleeding and all-cause death at 90 days than those with levels in the lowest quartiles. In patients with cancer, D-dimer levels failed to predict fatal PE or fatal bleeding., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpretable and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to evaluate the results in groups at risk for various cerebrovascular diseases., Material and Methods: Laboratory tests of aspirin resistance were performed in 79 patients with clinical non-responsiveness to aspirin treatment suffering from neurovascular diseases. Patients were divided into the two groups: expected low risk for aspirin resistance due to the first manifestation of a neurovascular disease (n = 34) and expected high risk due to the second clinical manifestation of a neurovascular disease (n = 45)., Results: The prevalence of aspirin resistance in both groups combined as determined by the PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was found between the two techniques., Conclusions: No significant prevalence of aspirin resistance was demonstrated by either method despite the heterogeneous pathophysiological mechanisms. However, we are presently unable to provide an accurate opinion on the value of laboratory test result or routine monitoring in clinical neurology.

Objectives: Our aim was to assess endothelial function in physically healthy patients with schizophrenia and related psychoses and to compare the results with healthy controls. Endothelial dysfunction was shown to predict future cardiovascular events in general population so we assumed to find a higher prevalence of endothelial dysfunction in patients with psychosis, as their cardiovascular morbidity is markedly higher than in general population, and to confirm the referred correlation with the traditional cardiovascular (CV) risk factors., Design: We assessed the traditional CV risk factors and endothelial function using non-invasive peripheral arterial tonometry (EndoPAT2000) in 50 stabilized and medicated schizophrenic patients (aged between 18 and 50 years) without any history of cardiovascular diseases and compared the results with 50 age-matched healthy controls., Setting: Psychiatric Clinic, University Hospital, Hradec Kralove and 2nd Department of Internal Medicine, General University Hospital, Prague, Czech Republic, Results: There was no difference in relative hyperaemia index as an endothelial function measure between patients and controls (2.19±0.68 vs. 1.98±0.57, p=NS) and there were also no correlations between reactive hyperaemia index and the traditional CV risk factors, illness duration or psychotic symptoms. On the other hand, the two study groups differed significantly in almost all traditional CV risk factors.

Background: The primary goal of the present study was to replicate our previous finding of increased coagulation and thrombocytes activity in drug-naïve psychotic patients in comparison with healthy controls and ascertain whether the blood levels of thrombogenesis markers further increase over the course of a consecutive one-year antipsychotic treatment., Subjects and Methods: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of nineteen men and seventeen women with acute psychosis (age 28.1±8.0 years, body mass index 22.6±4.2), and thirty-seven healthy volunteers matched for age, gender and body mass index. In the patient group, we repeated these assessments after three months and again after one year of antipsychotic treatment., Results: D-dimers (median 0.38 versus 0.19 mg/l; p=0.00008), factor VIII (median 141.5% versus 110%; p=0.02) and sP-selectin (median 183.6 versus 112.4 ng/ml; p=0.00005) plasma levels were significantly increased in the group of patients with acute psychosis prior to treatment compared with healthy volunteers. The plasma levels of sP-selectin varied significantly (p=0.016) in the course of the one-year antipsychotic treatment, mainly between 3 and 6 months after start of therapy. The plasma levels of D-dimers and factor VIII did not change significantly, D-dimers remained elevated in contrast to the healthy controls., Conclusions: Patients with acute psychosis had increased levels of markers of thrombogenesis in comparison to the healthy volunteers. The haemostatic parameters also remained elevated during the one-year antipsychotic treatment.

We report 2 cases of recurrent pulmonary embolism (PE) in popliteal venous aneurysm (PVA). Patients were 78-year-old and 72-year-old women. Both were initially seen for acute PE. Saccular and fusiform PVAs were diagnosed in each patient based on duplex ultrasound. However, despite anticoagulation therapy, both patients had PE. At the time of the event, 1 patient was receiving inadequate dose of low-molecular-weight heparin. The other patient was treated with warfarin and had adequate international normalized ratio at the time of re-embolism, and thus, an inferior vena cava filter was inserted. Both patients underwent successful aneurysm resection without any additional thromboembolic events.

The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first-generation low-potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second-generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Background: The natural history of unsuspected pulmonary embolism (PE) in patients with cancer has not been thoroughly studied., Methods: We used the RIETE Registry data to compare the clinical characteristics, treatment strategies and outcome in cancer patients with unsuspected PE and in those presenting with symptomatic, acute PE., Results: Up to December 2011, 78 cancer patients with unsuspected PE and 1,994 with symptomatic PE had been enrolled. Patients with unsuspected PE more likely had colorectal cancer than those with symptomatic PE (28% vs. 13%), and less likely had prostate (3.8% vs. 10%) or hematologic (1.3% vs. 6.4%) cancer, or prior venous thromboembolism (3.8% vs. 12%). While the patients were receiving anticoagulant therapy, the incidence of PE recurrences (0% vs. 1.9%) or major bleeding (2.6% vs. 4.8%) were similar. After completion of anticoagulation, recurrent PE developed in 2.6% vs. 1.4% of patients, and major bleeding in 0% vs. 0.4%, respectively., Conclusions: Our findings suggest that the clinical characteristics and outcome in cancer patients with unsuspected PE are quite similar to those in patients with symptomatic PE., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

To date, rheological treatment is the only chance to control the advanced dry form of age-related macular degeneration and arrest its progression to legal blindness. Rheohaemapheresis can change the main rheological parameters, blood and plasma viscosity, as well as change erythrocyte aggregability, improve erythrocyte flexibility and lead to substantial improvement when other methods of therapy fail. In this study, we describe changes in the levels of rheological efficacy indicators after rheohaemapheresis and their clinical significance in the dry form of age-related macular degeneration (AMD). Seventy-two patients with AMD were randomised; 34 controls, and 38 patients were treated with rheohaemapheresis (separator Cobe Spectra + Evaflux filter). After the procedures, α2-macroglobulin levels decreased by approximately 58%, fibrinogen by approximately 65%, IgM by approximately 67%, LDL cholesterol by approximately 71%, apolipoprotein B by approximately 65%, and lipoprotein (a) by approximately 42%. These decreases correspond with a decrease in blood and plasma viscosity (14/12%), clinical improvement (arrest of disease progression, even visual improvement in some cases), and heretofore-unreported improvement (even reattachment) of drusen retinal pigment epithelium detachment. Our modification of rheohaemapheresis is safe (5.4% of patients experienced clinically insignificant side effects).

Background: Antipsychotic treatment has been repeatedly found to be associated with an increased risk for venous thromboembolism in schizophrenia. The extent to which the propensity for venous thromboembolism is linked to antipsychotic medication alone or psychosis itself is unclear. The objective of this study was to determine whether markers of thrombogenesis are increased in psychotic patients who have not yet been treated with antipsychotic medication., Methods: We investigated the plasma levels of markers indicating activation of coagulation (D-dimers and Factor VIII) and platelets (soluble P-selectin, sP-selectin) in an antipsychotic-naive group of fourteen men and eleven women with acute psychosis (age 29.1 ± 8.3 years, body mass index 23.6 ± 4.7), and twenty-five healthy volunteers were matched for age, gender and body mass index., Results: D-dimers (median 0.38 versus 0.19 mg/l, mean 1.12 ± 2.38 versus 0.28 ± 0.3 mg/l; P = 0.003) and sP-selectin (median 204.1 versus 112.4 ng/ml, mean 209.9 ± 124 versus 124.1 ± 32; P = 0.0005) plasma levels were significantly increased in the group of patients with acute psychosis as compared with healthy volunteers. We found a trend (median 148% versus 110%, mean 160 ± 72.5 versus 123 ± 62.5; P = 0.062) of increased plasma levels of factor VIII in psychotic patients as compared with healthy volunteers., Conclusions: The results suggest that at least a part of venous thromboembolic events in patients with acute psychosis may be induced by pathogenic mechanisms related to psychosis rather than by antipsychotic treatment. Finding an exact cause for venous thromboembolism in psychotic patients is necessary for its effective treatment and prevention.

Unlabelled: Oral contraceptive use is a common risk factor for venous thromboembolism in women of reproductive age. The presence of inherited thrombophilia further increases this risk., Methods: We analyzed a large group of 400 Czech women with venous thromboembolism in association with oral contraceptive with regard to duration of use at the time of manifestation of venous thromboembolism, the frequency of inherited and acquired thrombophilia, the frequency of eliciting risk factor for thrombosis including immobilization, surgery, administration of plaster cast, long travel, and so on, and the type of thrombosis. The mean age of the women was 26 years, and the average duration of use was 45 months at the onset of thrombosis., Results: Venous thrombosis solely due to the pill occurred in 57% of the women, and in the other 43%, an additional transient eliciting factor was recognized. Among the clinical manifestation, distal thrombosis prevailed (N = 231, 58%) followed by proximal deep vein thrombosis (N = 65, 16%), pulmonary embolism (N = 21, 5%), and thrombosis in unusual sites (N = 20, 5%). Inherited or acquired thrombophilia was diagnosed in 195 (49%) women: factor V Leiden mutation in 35%, congenital deficiency of antithrombin in 1.8%, protein C in 0.8%, protein S in 1%, F IIG20210A in 5%, and antiphospholipid syndrome (APS) in 5.3%. Among the most common risk factors were immobilization of lower limb, minor and major surgery, and trauma., Conclusion: The results confirm that venous thromboembolism is a multifactorial disease in which thrombophilia screening is needed in young symptomatic women on the pill with thrombosis. The results also emphasize the value of proper thromboprophylaxis in women while on oral contraceptive in situations of increased risk for venous thromboembolism.

Myocarditis is a rare but life threatening adverse effect of clozapine. Some symptoms of myocarditis--elevated temperature, tachycardia and fatigue--appear commonly during the onset of treatment with clozapine and during the dose titration. We present a case of a patient with concurrent schizoaffective disorder and Parkinson's disease, who twice developed clozapine-induced myocarditis. All symptoms disappeared after the discontinuation of the drug. Early diagnosis, discontinuation of clozapine and supportive therapy of myocarditis lower the risk of a fatal outcome.

Rheological conditions basically influence tissue perfusion, oxygen and nutrient supply, tissue regeneration and in its consequence the course of pathological processes, especially in microcirculation and partially even in macrocirculation. Haemorheotherapy has shown to be successful in several indications (critical disorders in microcirculation) when other methods of therapy have failed. In this study we describe the changes of effectivity indicators in haemorheopheresis treatment and their clinical importance in cases of eye microcirculation, statoacoustic apparatus and disorders of the lower extremities. We treated with haemorheopheresis (separator Cobe.Spetra + Evaflux filter) 24 patients (16 patients with age related macular degeneration, 5 with critical peripheral arterial foot disease, and 3 with acute hearing loss). After the procedures alpha2-macroglobulin decreases by about 58%, fibrinogen by about 69%, IgM by about 61%, LDL-cholesterol by about 77%, apolipoprotein B by about 76% and lipoprotein(a) by about 63%. It corresponds with a decrease in blood and plasma viscosity and clinical improvement in the observed patients, i.e. visual improvement, acceleration of tissue defect healing and improvement in hearing. We noticed 7.1% clinically insignificant side-effects. The method of haemorheopheresis was safe. It led to improvement in patients' clinical condition in the above mentioned indications when other methods of treatment failed.

Aims: The aim of the present study was to compile a specific algorithm of prevention of venous thromboembolism in hospitalized psychiatric patients because this specific issue has not been addressed sufficiently in the literature., Methods: The computer database MEDLINE was searched using key words (schizophrenia OR depression OR bipolar) AND (antipsychotic OR antidepressant) AND (venous thromboembolism OR pulmonary embolism) AND (prevention OR prophylaxis) in 2006., Results: Based on the literature regarding non-surgical and surgical patients with respect to specificities in mental disorders (obesity induced with psychotropic drugs, possible catatonia, physical restraint, potential dehydration, antipsychotic treatment), a scoring system and a synoptic algorithm of prevention of venous thromboembolism modified for hospitalized psychiatric patients, were suggested., Conclusions: According to the authors' knowledge this is the first attempt to establish such guidelines exclusively in psychiatry. Individual preventative clinical measures are suggested, ranging from regular physical exercise of lower extremities to repeated parenteral application of high doses of heparin tailored to every patient's risk for venous thromboembolism. Economic data support implementation of a proposed decision procedure into psychiatric clinical practice. Prospective discussion of its international applicability would be beneficial from both the clinical and the scientific points of view.

Administration of antipsychotics appears to be related to increased risk of venous thromboembolism and cerebrovascular side effects. The biological mechanism responsible for this possible adverse drug reaction is unknown, but there is a growing number of elucidating hypotheses. Treatment with antipsychotics is associated with elevation of prolactin level. Prolactin has recently been recognized as potent platelet aggregation co-activator, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. We briefly review the arguments for the role of hyperprolactinemia in pathogenesis of platelet aggregation.

Objective. We assessed whether antipsychotic drugs represent a risk factor for venous thromboembolism by comparing the prevalence of antipsychotic drugs use in a population of patients with venous thromboembolism versus a group of individuals treated for hypertension. Methods. We identified 266 patients (141 women) diagnosed as having venous thromboembolism at the average age of 43.1±11 years who had been hospitalized in the University Hospital in Hradec Králové from 1 January 1996 to 31 December 2004. Two hundred and seventy-four patients (140 women) with arterial hypertension, with an average age of 48.3±8.8 years, represented the control population. Results. Use of antipsychotic drugs was moderately more frequent in the group of patients with venous thromboembolism as compared with the control group subjects (4.89 vs. 1.82%; odds ratio 2.76; 95% confidence interval=1.01-7.55). Discussion. We discuss the possible mechanisms of venous thromboembolism induced by antipsychotic agents - hypoactivity, blood status, obesity, abnormal coagulation, autoimmune mechanisms, and hyperhomocysteinemia. Conclusion. Our results indicate the possibility of an increased risk for venous thromboembolism in patients using antipsychotic drugs. It is necessary to seriously consider this possible adverse effect owing to its potentially fatal consequences.

Introduction: Thromboembolic complications are described in about 1% of the patients undergoing radiofrequency catheter ablation (RFA). The aim of this study was to analyze thrombotic complications after RFA and to determine prothrombotic states in patients with thrombotic complications., Methods: We analyzed data from 400 patients (212 females) who underwent 453 RFA procedures for supraventricular tachycardias. Transthoracic echocardiography was performed one day before and after RFA in all patients. We evaluated the clinical and laboratory (in patients with thrombotic complications after RFA) risk factors of thromboembolism., Results: We observed thrombotic complication in 7 (1.75%) patients (6 females), thrice flail thrombus in the right atrium, flail thrombus in the inferior vena cava, femoral vein thrombosis with massive pulmonary embolism, femoral vein mural thrombus and upper extremity digital arteries embolization; four of them were asymptomatic. As a prothrombotic state we identified factor V Leiden mutation in one case and the use of oral contraceptives in two cases. Two other patients had a positive history of thromboembolic events. In a subgroup of females the use of oral contraceptives (p = 0.13) or a positive history of thromboembolism (p = 0.21) were not identified as important risk factors., Conclusion: Echocardiographic detection of asymptomatic thrombotic complications contributed to the higher percentage of these complications in our study. Although we can identify the risk factor (laboratory or clinical) in a majority of patients with a thromboembolic complication, occurrence of these complications is unpredictable.