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Thrombotic complications are common in Coronavirus disease 2019 (COVID-19) patients, with pulmonary embolism (PE) being the most frequent. Randomised trials have provided inconclusive results on the optimal dosage of thromboprophylaxis in critically ill COVID-19 patients. We utilized data from the multicentre CAPACITY-COVID patient registry to assess the effect of differential application of Low Molecular Weight Heparin (LMWH) dose protocols on PE and in-hospital mortality risk in critically ill COVID-19 patients. An instrumental variable analysis was performed to estimate the intention-to-treat effect, utilizing differences in thromboprophylaxis prescribing behaviour between hospitals. We included 939 patients with PCR confirmed SARS-CoV-2 infection from 34 hospitals. Two-hundred-and-one patients (21%) developed a PE. The adjusted cause-specific HR of PE was 0.92 (95% CI: 0.73–1.16) per doubling of LMWH dose. The adjusted cause-specific HR for in-hospital mortality was 0.82 (95% CI: 0.65–1.02) per doubling of LMWH dose. This dose-response relationship was shown to be non-linear. To conclude, this study did not find evidence for an effect of LMWH dose on the risk of PE, but suggested a non-linear decreased risk of in-hospital mortality for higher doses of LMWH. However, uncertainty remains, and the dose-response relationship between LMWH dose and in-hospital mortality needs further investigation in well-designed studies.

Background Anticoagulation with warfarin represents a transportation‐sensitive treatment state. Transportation barrier is a common reason for not using health care services. Objective To assess the association between transportation barriers to anticoagulation clinic and anticoagulation control (AC) among an inner‐city, low‐income population. Patients/Methods Adults expected to be on chronic warfarin therapy were recruited from an ambulatory anticoagulation clinic. Participants completed a validated questionnaire that assessed transportation barriers to clinic, defined as self‐reported trouble getting transportation to a clinic and a composite score of the presence of transportation barriers. Suboptimal AC was defined as time in therapeutic range (TTR)

Background The rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and coronavirus disease 2019 (COVID-19), has caused more than 3.9 million cases worldwide. Currently, there is great interest to assess venous thrombosis prevalence, diagnosis, prevention, and management in patients with COVID-19. Objectives To determine the prevalence of venous thromboembolism (VTE) in critically ill patients with COVID-19, using lower limbs venous ultrasonography screening. Methods Beginning March 8, we enrolled 25 patients who were admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 infections. The presence of lower extremity deep vein thrombosis (DVT) was systematically assessed by ultrasonography between day 5 and 10 after admission. The data reported here are those available up to May 9, 2020. Results The mean (± standard deviation) age of the patients was 68 ± 11 years, and 64% were men. No patients had a history of VTE. During the ICU stay, 8 patients (32%) had a VTE; 6 (24%) a proximal DVT, and 5 (20%) a pulmonary embolism. The rate of symptomatic VTE was 24%, while 8% of patients had screen-detected DVT. Only those patients with a documented VTE received a therapeutic anticoagulant regimen. As of May 9, 2020, 5 patients had died (20%), 2 remained in the ICU (8%), and 18 were discharged (72%). Conclusions In critically ill patients with SARS-CoV-2 infections, DVT screening at days 5-10 of admission yielded a 32% prevalence of VTE. Seventy-five percent of events occurred before screening. Earlier screening might be effective in optimizing care in ICU patients with COVID-19.

Objectives To evaluate the impact of implemented procedures for out-of-hospital cardiac arrests (OHCAs) by determining patient outcome defined as the percentage return of spontaneous circulation at arrival at the emergency department, and 3-month and 1-year-survival rates. Design Observational study. Setting Primary emergency medical care consisting of Advanced Life Support is given by ambulance nurses and secondary care by hospitals within the mid-western part of the Netherlands covering 750 000 inhabitants. Participants 433 of 500 consecutive patients with OHCA were included in the study over a 1.5 -year period. Outcome measures Analysis included number of patients with return of spontaneous circulation (ROSC) when handed over to the emergency department, survival at 3 months and 1 year including a comparison with global outcome rates. We further considered the influence of gender, delays, bystander Basic Life Support, use of an automated external defibrillator, initial rhythm and mechanical thorax compression in combination with Boussignac tube ventilation. Results 13% (67/500) of the initial patient population was excluded from the analysis as reanimation in these patients was aborted due to expressed wish not to be resuscitated. Resuscitation was started by bystanders, police and/or first responders in 312/433 (72%) cases. An automated external defibrillator was used in 198 of these 312 cases (63%) of which it defibrillated 108 times. Mechanical thorax compression in combination with Boussignac tube ventilation was necessary in 277/433 patients (64%). Spontaneous circulation returned in 96/277 (35%) patients of this group. In the overall studied population, ROSC percentage at arrival at the hospital was 214/433 (49%). The 3-month and 12-month-survival rates were 123/433 (28%) and 119/433 (27%), respectively. Conclusions Optimised ‘chain of survival’ for patients with OHCA resulted in ROSC in 49% of the cases and a 1-year-survival rate of 27% in the studied population.

The effect of prophylaxis on the prevention of symptomatic venous thrombosis in patients with lower leg cast immobilisation or after knee arthroscopy is not clear. Our aim was to assess the current practice of thrombosis prophylaxis in Dutch hospitals and to determine considerations for prescribing prophylaxis.Electronic questionnaires regarding thrombosis prophylaxis in patients with lower leg cast immobilisation or after knee arthroscopy were sent to all orthopaedic (90) and trauma surgery departments (89) and orthopaedic clinics (16) in the Netherlands.Response rate was 88% for orthopaedic surgery departments/clinics and 81% for trauma surgery departments. Analysis of the questionnaires reveals that prophylaxis was not provided for patients with lower leg cast immobilisation at only 3 (4%) orthopaedic and 3 (4%) trauma surgery departments, while 10 (11%) orthopaedic surgery departments did not provide prophylaxis for patients undergoing knee arthroscopies. Substantial differences in prophylactic strategies were observed as these strategies were dependent on both the indication for treatment and on the presence of concomitant risk factors for venous thrombosis. The most reported rationales for prescribing prophylaxis were: the perceived risk reduction of prophylaxis outweighs the bleeding risk; the experience that prophylaxis is effective; to act in accordance with hospital guidelines.Despite the lack of a solid evidence base, it seems that the large majority of patients with lower leg cast immobilisations, along with those undergoing knee arthroscopy, do receive thrombosis prophylaxis. However, depending on the indications, large variations within prophylaxis strategies seem to exist, which demonstrate the need for an evidence-based uniform prophylaxis scheme.

Outpatients with cancer have an increased risk of venous thrombosis, especially during chemotherapy. Clinical trials have shown that thromboprophylaxis with low-molecular-weight heparin reduces the incidence of symptomatic venous thrombosis in these patients. An increase in major bleeding events was suggested but not confirmed in most recent trials. However, as the incidence of venous thrombosis is relatively low in the general cancer population, thromboprophylaxis should not be recommended for all cancer outpatients. Instead, to optimize the risk/benefit ratio, targeted thromboprophylaxis for patients deemed at high risk is recommended. Risk prediction models may be used to identify these high risk patients. Until results of clinical trials based on these models are published, thromboprophylaxis can be considered in patients with advanced or metastatic high risk cancers (e.g. pancreatic and lung cancer) who are receiving chemotherapy and have no increased risk of bleeding. Because of the many uncertainties, the decision to start thromboprophylaxis should always be discussed with the patient.

Oral anticoagulant therapy has been shown to be effective for several indications. The optimal intensity of anticoagulation for each indication, however, is largely unknown. To determine this optimal intensity, randomised clinical trials are conducted in which two target levels of anticoagulation are compared. This approach is inefficient, since the choice of the target levels will be arbitrary. Moreover, the achieved intensity is not taken into account. We propose a method to determine the optimal achieved intensity of anticoagulation. This method can be applied within a clinical trial as an "efficacy-analysis", but also on data gathered in day-to-day patient care. In this method, INR-specific incidence rates of events, either thromboembolic or hemorrhagic, are calculated. The numerator of the incidence rate is based on data on the INR at the time of the event. The denominator consists of the person-time at each INR value, summed over all patients, and is calculated from all INR measurements of all patients during the follow-up interval. This INR-specific person-time is calculated with the assumption of a linear increase or decrease between two consecutive INR determinations. Since the incidence rates may be substratified on covariates, efficient assessment of the effects of other factors (e.g. age, sex, comedication) by multivariate regression analysis becomes possible. This method allows the determination of the optimal pharmacological effects of anticoagulation, which can form a rational starting point for choosing the target levels in subsequent clinical trials.

Outra Agência A trombose venosa profunda (TVP) e o tromboembolismo pulmonar (TEP) são as principais manifestações clínicas do tromboembolismo venoso (TEV). O TEV é uma complicação comum e potencialmente grave das cirurgias ortopédicas, uma vez que pode levar à limitação funcional e morte pós-operatória. O uso da tromboprofilaxia reduz acentuadamente a incidência de TEV relacionado às intervenções ortopédicas, e seu uso é recomendado por diversas diretrizes. Entretanto, a indicação e o tipo de tromboprofilaxia para algumas intervenções ortopédicas, assim como o uso de ferramentas de predição de risco, ainda não estão bem estabelecidos e constituem pontos de debate. Os objetivos deste trabalho foram identificar os fatores de risco para TEV e suas interações nas cirurgias ortopédicas e avaliar a aplicabilidade do escore de risco de Caprini na predição de TEV em pacientes ortopédicos. Além disso, devido à escassez de conhecimento e recomendações sobre tromboprofilaxia nas intervenções ortopédicas de tornozelo e pé, realizaram-se uma revisão narrativa e uma enquete internacional sobre o assunto. Para analisar a interação de fatores de risco de TEV e a aplicabilidade preditiva do escore de Caprini nas cirurgias ortopédicas, foram utilizados os dados do Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA), um estudo caso-controle holandês de base populacional cujo desfecho de interesse é o TEV. Neste, 263 indivíduos que tiveram TEV e 94 controles foram submetidos à cirurgia ortopédica. O risco de TEV foi maior nos primeiros 30 dias após a cirurgia [odds ratio ajustada (ORadj) 17,5; intervalo de confiança (IC) 95%, 9,2-33,4] e manteve-se aumentado até 90 dias (ORadj 11,5; IC 95%, 7,3-17,7). Houve interação entre cirurgia ortopédica e mutação fator V Leiden (ORadj 17,5; IC 95%, 4,1-73,6), tipo de sangue não-O (ORadj 11,2; 95% IC, 3,4-34,0) e níveis séricos de fator VIII maiores que 150 mg/dl (ORadj 18,6; IC, 7,4-46,9). Quanto ao escore de Caprini, foram avaliados 357 indivíduos com TEV submetidos à cirurgia ortopédica. Um total de 20,9% dos casos e 41,5% dos controles foram classificados no grupo de menor risco (Caprini < 5 pontos). Pacientes com um escore de Caprini maior que 11 pontos tiveram um risco de TEV seis vezes maior (OR 6,3; IC 95%, 1,7-22,9), e pacientes com um escore de 9 a 10 tiveram um risco três vezes maior (OR 3,5; IC 95% 1,2-10,3). A área sob a curva (AUC) do escore de Caprini foi de 0,64, evidenciando uma discriminação de predição de TEV moderada. Na enquete internacional sobre tromboprofilaxia de pé e tornozelo, 693 cirurgiões ortopédicos de pé e tornozelo de 49 países participaram. Aproximadamente 50% informaram prescrever tromboprofilaxia durante a imobilização do paciente. Quando utilizada, as escolhas preferidas em ordem decrescente foram ácido acetilsalicílico (AAS), heparina de baixo peso molecular (HBPM) e anticoagulantes orais diretos. AAS e HBPM foram predominantemente prescritos na América do Norte e Europa, respectivamente. TVP prévia, imobilidade, obesidade e trombofilia hereditária foram considerados os principais fatores de risco indicativos do uso de tromboprofilaxia. Concluiu-se que: houve risco aumentado de TEV e interação entre os fatores de risco fator V Leiden, níveis elevados de fator VIII e grupo sanguíneo não- O com cirurgia ortopédica; o escore de Caprini é uma ferramenta que pode auxiliar os cirurgiões ortopédicos a classificarem o risco de TEV no pós-operatório, embora seu desempenho preditivo discriminativo tenha sido moderado; apesar de a maioria dos cirurgiões ortopédicos de tornozelo e pé considerarem que a tromboprofilaxia está indicada para cirurgias de tornozelo e pé (principalmente na presença de fatores de risco como TVP prévia, imobilidade, obesidade e trombofilia hereditária), a prescrição, o tipo e a duração apresentam grande discrepância intercontinental. Assim, este trabalho contribui para a identificação de pacientes sob alto risco de TEV, ponto estratégico para o uso individualizado e seguro da tromboprofilaxia como ferramenta para redução do risco de TEV relacionado às cirurgias ortopédicas. Deep vein thrombosis (DVT) and pulmonary embolism are the main clinical manifestations of venous thromboembolism (VTE). VTE is a common and potentially serious complication of orthopedic surgeries, as it can lead to functional limitation and postoperative death. The use of thromboprophylaxis markedly reduces the incidence of VTE related to orthopedic interventions, and its use is recommended by several guidelines. However, the indication and type of thromboprophylaxis for some orthopedic interventions, as well as the use of risk prediction tools are still not well established and is debatable. The objectives of this study were to identify risk factors for VTE and their interactions in orthopedic surgeries and to evaluate the applicability of the Caprini risk score in predicting VTE in orthopedic patients. In addition, due to the lack of knowledge and recommendations on thromboprophylaxis in foot and ankle surgeries, a narrative review and an international survey on the subject were carried out. Data from the MEGA Study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis) which is a Dutch population-based case-control study whose outcome of interest is VTE were used. A total of 263 subjects who had VTE and 94 controls underwent orthopedic surgery. The risk of VTE was the highest in the first 30 days after surgery (adjusted odds ratio [ORadj] 17.5; 95% CI [confidence interval], 9.2-33.4) and remained increased up to 90 days (ORadj, 11.5; 95% CI, 7.3- 17.7). There was interaction between orthopedic surgery and factor V Leiden mutation (ORadj 17.5, 95%CI 4.1-73.6), non-O blood type (ORadj 11.2; 95%CI 3.4-34.0) and factor VIII plasma levels greater than 150 mg/dl (ORadj 18.6; CI 7.4-46.9). To assess the applicability of the Caprini Score, 357 individuals with VTE undergoing orthopedic surgery in the MEGA were evaluated. A total of 20.9% of cases and 41.5% of controls were classified in the lowest risk group (Caprini