Venous thromboembolism in amyotrophic lateral sclerosis: a prospective study.

Venous thromboembolism prophylaxis: do trial results enable clinicians and patients to evaluate whether the benefits justify the risk? proceedings of an ad hoc working group meeting

Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy.

This meta-analysis was designed to compare the incidence of deep vein thrombosis (DVT) and venous thromboembolism (VTE) following total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). All studies directly comparing the post-TKA incidence of DVT and/or VTE in patients with RA and OA were included. For all comparisons, odds ratios and 95% confidence intervals (CI) were calculated for binary outcomes. Six studies were included in the meta-analysis. The pooled data showed that the combined rates of asymptomatic and symptomatic DVT did not differ significantly in the RA and OA groups (1065/222,714 [0.5%] vs. 35,983/6,959,157 [0.5%]; OR 0.77, 95% CI: 0.57 to 1.02; P = 0.07). The combined rates of asymptomatic and symptomatic DVT and pulmonary embolism (PE) after TKA were significantly lower in the RA than in the OA group (1831/225,406 [0.8%] vs. 63,953/7,018,721 [0.9%]; OR 0.76, 95% CI: 0.62 to 0.93; P = 0.008). Conclusiviely, the DVT rates after primary TKA were similar in RA and OA patients. In contrast, the incidence of VTE (DVT plus PE) after primary TKA was lower in RA than in OA patients, despite patients with RA being at theoretically higher risk of thrombi due to chronic inflammation.

Введение. Тромбозы глубоких вен (ТГВ) являются нередким осложнением течения и лечения у детей с заболеваниями крови и требуют проведения антитромботической терапии и профилактики для снижения количества повторных тромботических эпизодов. Цель исследования: анализ частоты и определение факторов риска повторных ТГВ у детей, госпитализированных для лечения заболеваний крови. Материалы и методы. Проведен ретроспективный анализ электронной базы данных пациентов в возрасте от 0 до 17 лет включительно, которым проводили стационарное лечение гемобластозов и синдромов костномозговой недостаточности в период 01.0.2012 по 31.12.2017. В анализ вошли только те пациенты, у которых было зарегистрировано более 1 случая тромбоза. Результаты. Рецидивы тромбозов наблюдали у 13,3 детей с асимптоматическими (аТГВ) и у 5,4 с симптоматическими (сТГВ) ТГВ. Рецидивы аТГВ при остром лимфобластном лейкозе (ОЛЛ) выявлены у 14,5, при остром миелобластном лейкозе (ОМЛ) у 8,9, при лимфоме у 11,9. У детей с сТГВ рецидивы тромбоза выявлены при ОЛЛ у 8,2, при ОМЛ у 8,3, при лимфоме у 2,8 пациентов. Медиана возраста пациентов с единственным эпизодом сТГВ составила 10 лет, с рецидивом сТГВ 9 лет, при аТГВ 7 лет для пациентов с единственным эпизодом и 6 лет с рецидивом аТГВ. Некорректно проведенная терапия была зарегистрирована у 50 детей. Заключение. Рецидивирующее течение тромбоза у детей, госпитализированных для лечения заболеваний крови, уста новлено у 5,4 детей с сТГВ и у 13,3 детей с аТГВ, причем 1/3 часть сТГВ является потенциально жизнеугрожающей. Полученные данные подчеркивают необходимость проведения вторичной антитромботической профилактики у детей с ТГВ и ставят вопрос о необходимости и целесообразности проведения таковой у пациентов с аТГВ. Introduction. Deep vein thrombosis (DVT) remains a common complication of hematological diseases in children and requires antithrombotic therapy and prophylaxis of recurrent thrombotic events. Aim: to determine incidence and risk factors of recurrent DVT for hospitalized children with blood diseases. Materials and methods. Medical records of patients hospitalized with oncohematological diseases and bone marrow aplasia, aged from 0 to 17 years, were analyzed retrospectively. Only patients with more than one DVT were taken into this analysis. Results. Recurrent DVT was diagnosed in 13.27 children with asymptomatic DVT (aDVT) and in 5.41 with symptomatic DVT (sDVT). Recurrent DVT was found in 14.49 children with acute lymphoblastic leukemia (ALL), in 8.89 with acute myeloblastic leukaemia (AML), in 11.86 with lymphomas. Incidence of recurrent thrombosis in children with sDVT was 8.16 for ALL, 8.33 for AML, 2.78 for lymphomas. Age analysis of patients with the single episode and recurrent thrombosis showed that age median with single sDVT was 10 years, recurrent DVT 9 years, in case of single asymptomatic or incidental (aDVT) episode 7 years, recurrent DVT 6 years. Incorrect therapy was registered for 50 of children with recurrent sDVT. Conclusion. Recurrent DVT in hospitalized children with blood diseases occurred in 5.41 children with sDVT and in children 13.33 with aDVT 1/3 episodes of sDVT was lifethreatening. In conclusion, secondary prophylaxis is needed for children with DVT and future research should be done for prophylaxis in those with aDVT.

Factor V Leiden (FVL) supposedly carries relatively higher risk of deep vein thrombosis (DVT), compared to the risk of pulmonary embolism (PE). To prove this paradox in a group of patients with various clinical presentation of venous thromboembolism (VTE). We retrospectively evaluated clinical pattern of VTE in patients who had been referred to vascular clinic shortly after an acute VTE event. In FVL positive and FVL negative groups we compared the prevalence of isolated symptomatic DVT (proximal or distal) and symptomatic PE with/without DVT, and, moreover, asymptomatic DVT or PE. Of 575 patients (mean age 57 years, 50.1% women), 120 were FVL positive and those had significantly higher prevalence of isolated symptomatic DVT, compared to symptomatic PE with/without DVT. Proximal DVT location was significantly more frequent in FVL carriers. The prevalence of asymptomatic PE did not differ between the two groups. The rate of asymptomatic DVT tended to be higher in FVL negative group. In a multivariate analysis, we confirmed FVL to be positively associated with isolated DVT presentation (odds ratio OR 1.757; 95% confidence interval (CI) 1.148-2.690). On the contrary, increasing age and unprovoked nature of VTE event carried a higher risk of symptomatic PE. We confirmed FVL to be significantly associated with isolated symptomatic DVT despite higher prevalence of proximal DVT in FVL carriers. The fact of relatively lower risk of PE in FVL positive patients might have clinical implication. However, mechanisms of FVL paradox remain to be elucidated.

### Learning objectives Thrombosis is the common pathophysiology responsible for ischaemic heart disease, ischaemic stroke and venous thromboembolism (VTE), and a major contributor to the global disease burden.1 This effect...

Postoperative Deep Vein Thrombosis (DVT) In Patients With Hemophilia Undergoing Major Orthopedic Surgery

Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis. Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation-perfusion (V/Q) scan to screen for incidental pulmonary embolism. Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported. In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.

Symptomatic venous thromboembolism (VTE) after total or partial knee arthroplasty (TPKA) and after total or partial hip arthroplasty (TPHA) are proposed patient safety indicators, but its incidence prior to discharge is not defined. To establish a literature-based estimate of symptomatic VTE event rates prior to hospital discharge in patients undergoing TPHA or TPKA. Search of MEDLINE, EMBASE, and the Cochrane Library (1996 to 2011), supplemented by relevant articles. Reports of incidence of symptomatic postoperative pulmonary embolism or deep vein thrombosis (DVT) before hospital discharge in patients who received VTE prophylaxis with either a low-molecular-weight heparin or a subcutaneous factor Xa inhibitor or oral direct inhibitor of factors Xa or IIa. Meta-analysis of randomized clinical trials and observational studies that reported rates of postoperative symptomatic VTE in patients who received recommended VTE prophylaxis after undergoing TPHA or TPKA. Data were independently extracted by 2 analysts, and pooled incidence rates of VTE, DVT, and pulmonary embolism were estimated using random-effects models. The analysis included 44,844 cases provided by 47 studies. The pooled rates of symptomatic postoperative VTE before hospital discharge were 1.09% (95% CI, 0.85%-1.33%) for patients undergoing TPKA and 0.53% (95% CI, 0.35%-0.70%) for those undergoing TPHA. The pooled rates of symptomatic DVT were 0.63% (95% CI, 0.47%-0.78%) for knee arthroplasty and 0.26% (95% CI, 0.14%-0.37%) for hip arthroplasty. The pooled rates for pulmonary embolism were 0.27% (95% CI, 0.16%-0.38%) for knee arthroplasty and 0.14% (95% CI, 0.07%-0.21%) for hip arthroplasty. There was significant heterogeneity for the pooled incidence rates of symptomatic postoperative VTE in TPKA studies but less heterogeneity for DVT and pulmonary embolism in TPKA studies and for VTE, DVT, and pulmonary embolism in TPHA studies. Using current VTE prophylaxis, approximately 1 in 100 patients undergoing TPKA and approximately 1 in 200 patients undergoing TPHA develops symptomatic VTE prior to hospital discharge.

Among patients with isolated below-knee fractures, previous studies have detected asymptomatic deep vein thrombosis in 10%-40% using contrast venography. However, the clinical relevance of these thrombi is unknown; there is considerable uncertainty about the risk: benefit of routine thromboprophylaxis and clinical practice guidelines differ in their recommendations. In this multicenter, double-blind trial, 265 patients with isolated lower leg fractures requiring surgery were randomized to subcutaneous dalteparin 5000 units or matching placebo once daily for 2 weeks with bilateral Doppler ultrasound (DUS) of the proximal leg veins on postoperative day 14±2 and 3-month follow-up. The primary effectiveness outcome was clinically important venous thromboembolism (CIVTE), defined as the composite of symptomatic venous thromboembolism within 3 months after surgery and asymptomatic proximal deep vein thrombosis on DUS. The primary safety outcome was major bleeding. Two hundred fifty-eight patients (97%) were included in the primary outcome analysis for effectiveness (130: dalteparin; 128: placebo). Incidence of CIVTE in the dalteparin and placebo groups was 1.5% and 2.3%, respectively (absolute risk reduction, 0.8%; 95% confidence interval, -2.0 to 3.0). There were no fatal pulmonary emboli or major bleeding. The overall incidence of CIVTE after surgically repaired, isolated tibia, fibula, and ankle fractures was low (1.9%; 95% confidence interval, 0.7-4.7), with no observed differences between dalteparin and placebo either for CIVTE or safety. Recruitment was stopped at the first interim analysis. This study also demonstrates the substantial discrepancy in venous thromboembolism rates between trials that use venographic outcomes compared with more clinically relevant outcomes. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Venous Thromboembolism (VTE) in Hematological and Non-Hematological Cancers: A Nationwide Analysis

Amyotrophic lateral sclerosis (ALS) is a degenerative neuromuscular disease with marked clinical heterogeneity. This heterogeneity can be partly captured by clinical measures, such as the forced vital capacity (FVC) and ALS Functional Rating Scale-Revised (ALSFRS-R). We aimed to further characterize the performance of these clinical measures, including their independence and additivity, in predicting mortality. We leveraged the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT ALS) database, which includes data from 23 clinical trials (n =2050). The primary exposures were baseline FVC and ALSFRS-R. The primary outcome was 1-y mortality. We performed correlation analyses, survival analyses and assessed classification performance using receiver operator characteristic (ROC) curves. FVC and ALSFRS-R were weakly correlated (r=0.31, p< .001). A 1-SD increase in FVC (hazard ratio [HR]: 0.66; 95% confidence interval [CI]: 0.59-0.74) and ALSFRS-R (HR: 0.75; 95% CI: 0.68-0.82) were associated with reduced risk of 1-y mortality. ROC analyses showed optimal predictive cutoffs at 80% for FVC (area under the curve [AUC]: 0.69) and 38 for ALSFRS-R (AUC: 0.67). After stratifying patients based on these cutoffs, we found a marked reduction (HR: 0.25; 95% CI: 0.19-0.33) in incident mortality for patients in the high FVC and high ALSFRS-R group relative to the low FVC and low ALSFRS-R group. ALSFRS-R and FVC are comparable predictors of survival that are only weakly correlated. When considered together, they synergistically predict survival. As such, consideration of both measures should be a routine part of prognostication in care of patients with ALS.

Recurrence and Mortality of DVT-Associated PE Is Greater Than Isolated PE Alone: Results of the 7532-Patients Prospective OPTIMEV Cohort Study.

High Mortality After Venous Thromboembolism: A Population-Based Cohort Study

Asymptomatic deep-vein thrombosis (DVT) detected by mandatory venography, a surrogate outcome, comprises most of the efficacy outcome events in recent thromboprophylaxis trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in these clinical trials requires a consistent relationship between asymptomatic DVT and symptomatic venous thromboembolism (VTE). In this systematic review of high quality VTE prevention trials, we examined the consistency of the ratios of asymptomatic DVT to symptomatic VTE across a broad range of indications. Studies were identified from citations listed in the chapters on VTE prevention in the antithrombotic guidelines by the American College of Chest Physicians, 2012. A study was eligible if it: 1) was a randomised trial comparing an anticoagulant with standard of care; 2) included at least 500 participants; 3) reported asymptomatic or all DVT rates; and 4) reported symptomatic VTE rates. Of the 26 eligible trials, 19 trials were conducted in orthopaedic patients, five in general surgery patients and two in general medical patients. The overall median rates (ranges) for asymptomatic DVT and symptomatic VTE were 9.11 % (0.75 to 54.87 %) and 0.49 % (0.00 to 3.10 %), respectively. The median ratio was 14.53, with a wide range (2.75 to 103.86). Wide variability in the ratios persisted despite indication- and anticoagulant-specific analyses. In VTE prevention trials of alternative anticoagulants, the wide variability in the ratios of asymptomatic DVT to symptomatic VTE precludes judging the trade-off between thrombotic and bleeding events on the basis of composite outcomes dominated by venographic DVT.