RISK OF THROMBOEMBOLISM AFTER COVID-19 VACCINATION AND COVID-19 INFECTION. (preprint)

Background: Vaccine safety monitoring systems worldwide have reported cases of venous thromboembolism and arterial thromboembolism following a COVID-19 vaccination. However, evidence shows that the association between thromboembolism and SARS-CoV-2 infection is stronger, compared to SARS-CoV-2 vaccination. Hence, weighing the risks and benefits of vaccination should also encounter the roles of vaccination in reducing infection rate, and potentially indirectly lowering the risk of thromboembolism caused by infection. Methods: We conducted a self-controlled case series study (SCCS) from Dec 1st 2020 to 31st August 2022 (before the bivalent vaccine was available) to examinate the association between the first two doses Pfizer/Moderna vaccination and thrombotic events among patients in Corewell Health East (CHE, formerly known as Beaumont Health) healthcare system. We also investigated the effect SARS-CoV-2 infection on the risk of thrombosis events and observed a significant increased risk using the SCCS design. However, because of misclassification bias, SCCS indeed overestimated incidence rate ratio (IRR) of acute event after infection, we then proposed a case-control study addressing this misclassification issues and obtained odd ratio comparing effect of exposure on thrombosis and a subset of controls group. Finally, we analyzed the risk of thromboembolism between vaccinated and unvaccinated groups by a simple diagram, explaining possible factors that affects the probability of experiencing an acute thromboembolism event after a COVID-19 vaccination. Results: Using EHR data at Corewell East, we found an increased risk of thrombosis after the first two doses of COVID-19 vaccination, with incidence rate ratios after the first dose is 1.16 (CI: [1.04, 1.29]), and after the second dose of 1.19 (CI: [1.07,1.32]). The association between thromboembolism and SARS-Cov-2 infection depends on prior vaccination status, as the conditional OR among unvaccinated and vaccinated groups are 1.77 (CI: [1.48,\ 2.1]) and 1.34 (CI: [1.09,\ 1.66]) respectively. Encountering the vaccine efficacy (VE), receiving the COVID-19 vaccine decreases the risk of thromboembolism, and the benefits of COVID-19 vaccines are much stronger in the period of high infection rate.

Long-term cardiovascular safety of COVID-19 vaccination according to brand, dose and combinations: Cohort study of 46 million adults in England (preprint)

Using longitudinal health records from 45.7 million adults in England followed for a year, our study compared the incidence of thrombotic and cardiovascular complications after first, second and booster doses of brands and combinations of COVID-19 vaccines used during the first two years of the UK vaccination program with the incidence before or without the corresponding vaccination. The incidence of common arterial thrombotic events (mainly acute myocardial infarction and ischaemic stroke) was generally lower after each vaccine dose, brand and combination. Similarly, the incidence of common venous thrombotic events, (mainly pulmonary embolism and lower limb deep venous thrombosis) was lower after vaccination. There was a higher incidence of previously reported rare harms after vaccination: vaccine-induced thrombotic thrombocytopenia after first ChAdOx1 vaccination, and myocarditis and pericarditis after first, second and transiently after booster mRNA vaccination (BNT-162b2 and mRNA- 1273) These findings support the wide uptake of future COVID-19 vaccination programs.

Covid-19 vaccine safety in pregnancy, a nested case-control study in births from April 2021 to March 2022, England (preprint)

Introduction: Vaccine safety in pregnancy is always of paramount importance. Current evidence of COVID-19 vaccine safety in pregnancy has been reassuring with no association found with negative maternal and neonatal outcomes. However, very few safety studies are conducted on a national level and investigate dosage, timing of vaccination as well as vaccine manufacturer. To fill this knowledge gap, we conducted a population based COVID-19 vaccine safety evaluation in England, including timing of vaccination by trimester, dosage and vaccine manufacturer received in pregnancy. Method: A matched case control study nested in a retrospective cohort where adverse maternal and neonatal pregnancy outcomes were compared across several COVID-19 vaccine exposures using conditional multivariable logistic regression, adjusting for a range of demographic and health characteristics. Eligible participants were identified from the national maternity services dataset (MSDS) and records were linked to hospital admission, national COVID-19 vaccine and COVID-19 testing databases. Matching criteria differed by outcome but included participant's age and estimated week of conception. Results: 514,013 pregnant individuals aged between 18 and 50 years were identified during the study period (births from 16th of April 2021- 31st March 2022). Receiving at least one dose of COVID-19 vaccine during pregnancy conferred lower odds of giving birth to a baby who was low birthweight (aOR=0.86, 95% CI: 0.79 - 0.93), preterm (aOR=0.89, 95% CI: 0.85 - 0.92) or who had an Apgar score less than 7 at five mins of age (aOR=0.89, 95% CI: 0.80 - 0.98). There was no association between vaccination in pregnancy and stillbirth (aOR=0.90, 95% CI: 0.76 - 1.07), neonatal death (aOR=1.27, 95% CI: 0.91 - 1.77) perinatal death (aOR=0.98, 95% CI: 0.83 - 1.16), and maternal venous thromboembolism in pregnancy (aOR=0.82, 95% CI: 0.43 - 1.56). The odds of maternal admission to intensive care unit were lower in vaccinated pregnant women (aOR=0.85, 95% CI: 0.76 - 0.95). Conclusion: COVID-19 vaccines are safe to use in pregnancy and they confer protection against SARS-CoV-2 infection which can lead to adverse outcomes for both the mother and the infant. Our findings generated important information to communicate to pregnant women and health professionals to support COVID-19 maternal vaccination programmes.

The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study (preprint)

ImportanceThe overall effects of vaccination on the risk of cardiac, and venous and arterial thromboembolic complications following COVID-19 remain unclear. ObjectiveWe studied the association between COVID-19 vaccination and the risk of acute and subacute COVID-19 cardiac and thromboembolic complications. DesignMultinational staggered cohort study, based on national vaccination campaign rollouts. SettingNetwork study using electronic health records from primary care records from the UK, primary care data linked to hospital data from Spain, and national insurance claims from Estonia. ParticipantsAll adults with a prior medical history of [≥]180 days, with no history of COVID-19 or previous COVID-19 vaccination at the beginning of vaccine rollout were eligible. ExposureVaccination status was used as a time-varying exposure. Vaccinated individuals were classified by vaccine brand according to the first dose received. Main OutcomesPost COVID-19 complications including myocarditis, pericarditis, arrhythmia, heart failure (HF), venous (VTE) and arterial thromboembolism (ATE) up to 1 year after SARS-CoV-2 infection. MeasuresPropensity Score overlap weighting and empirical calibration based on negative control outcomes were used to minimise bias due to observed and unobserved confounding, respectively. Fine-Gray models were fitted to estimate sub-distribution Hazard Ratios (sHR) for each outcome according to vaccination status. Random effect meta-analyses were conducted across staggered cohorts and databases. ResultsOverall, 10.17 million vaccinated and 10.39 million unvaccinated people were included. Vaccination was consistently associated with reduced risks of acute (30-day) and subacute post COVID-19 VTE and HF: e.g., meta-analytic sHR 0.34 (95%CI, 0.27-0.44) and 0.59 (0.50-0.70) respectively for 0-30 days, sHR 0.58 (0.48 - 0.69) and 0.71 (0.59 - 0.85) respectively for 90-180 days post COVID-19. Additionally, reduced risks of ATE, myocarditis/pericarditis and arrhythmia were seen, but mostly in the acute phase (0-30 days post COVID-19). ConclusionsCOVID-19 vaccination reduced the risk of post COVID-19 complications, including cardiac and thromboembolic outcomes. These effects were more pronounced for acute (1-month) post COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough vs unvaccinated SARS-CoV-2 infection. RelevanceThese findings highlight the importance of COVID-19 vaccination to prevent cardiovascular outcomes after COVID-19, beyond respiratory disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of COVID-19 vaccination to prevent cardiac complications and thromboembolic events following a SARS-CoV-2 infection? FindingsResults from this multinational cohort study showed that COVID-19 vaccination reduced risk for acute and subacute COVID-19 heart failure, as well as venous and arterial thromboembolic events following SARS-CoV-2 infection. MeaningThese findings highlight yet another benefit of vaccination against COVID-19, and support the recommendations for COVID-19 vaccination even in people at high cardiovascular risk.

A review of venous thromboembolism in India.

Venous thromboembolism (VTE), which entails the formation of a thrombus (blood clot) in a vein, has a significant disease burden worldwide. While VTE has traditionally been considered to predominantly affect Caucasian populations, recent studies have indicated a gradual shift in the disease burden towards Asian populations, with added significance of it being a key driver of post-operative mortality. It is imperative to develop a sound understanding of the various factors that affect VTE in stratified local populations. However, there is a glaring paucity of quality data on VTE and its ramifications among Indians - both in terms of quality of life and cost of healthcare. This review aims to throw light on the disease burden, epidemiology, risk factors, environmental factors, food and nutrition that plays a key role in VTE. We also explored the association of VTE with coronavirus disease 2019 to grasp the interplay between the two most significant public health crises of our time. It is vital to place a special emphasis on future research on VTE in India to plug the gaps, which exist in our current knowledge of the disease, particularly with respect to Indian population.

Unchanged Characteristics and Survival among Critically Ill COVID-19 Patients during First, Second, and Third Waves: A Prospective Observational Cohort.

BACKGROUND: This study was carried out to compare characteristics and outcomes in patients with acute respiratory failure related to COVID-19 during first, second, and third waves. METHODS: We included consecutive adults admitted to the intensive care unit between March 2020 and July 2021. We compared three groups defined by the epidemic intake phase: waves 1 (W1), 2 (W2), and 3 (W3). RESULTS: We included 289 patients. Two hundred and eight (72%) patients were men with a median age of 63 years (IQR: 54-72), of whom 68 (23.6%) died in hospital. High-flow nasal oxygen (HFNO) was inversely associated with the need for invasive mechanical ventilation (MV) in multivariate analysis (p = 0.003) but not dexamethasone (p = 0.25). The day-90 mortality rate did not vary from W1 (27.4%) to W2 (23.9%) and W3 (22%), p = 0.67. By multivariate analysis, older age (odds ratio [OR]: 0.94/year, p < 0.001), immunodeficiency (OR: 0.33, p = 0.04), acute kidney injury (OR: 0.26, p < 0.001), and invasive MV (OR: 0.13, p < 0.001) were inversely associated with higher day-90 survival as opposed to the use of intermediate heparin thromboprophylaxis dose (OR: 3.21, p = 0.006). HFNO use and dexamethasone were not associated with higher day-90 survival (p = 0.24 and p = 0.56, respectively). CONCLUSIONS: In patients with acute respiratory failure due to COVID-19, survival did not change between first, second, and third waves while the use of invasive MV decreased. HFNO or intravenous steroids were not associated with better outcomes, whereas the use of intermediate dose of heparin for thromboprophylaxis was associated with higher day-90 survival. Larger multicentric studies are needed to confirm our findings.

Antithrombotic therapy in the management of hospitalised patients with COVID-19.

Hospitalised patients with coronavirus disease 2019 (COVID-19) are at a significantly higher risk of having thromboembolic events while in hospital and in the immediate post-hospital discharge period. Based on early data from observational studies, multiple high quality randomised controlled trials have been conducted worldwide to evaluate optimal thromboprophylaxis regimens to reduce thromboembolism and other COVID-19-related adverse outcomes in hospitalised patients. The International Society on Thrombosis and Haemostasis has published evidence-based guideline recommendations using established methodology for the management of antithrombotic therapy of COVID-19 patients, both in-hospital and in the immediate post-hospital discharge period. A good clinical practice statement supplemented these guidelines based on topics for which there was no or limited high-quality evidence. This review summarises the main recommendations of these documents to serve as a quick access tool for hospital doctors to use in their everyday practice when treating COVID-19 patients.

Integral assays of hemostasis in hospitalized patients with COVID-19 on admission and during heparin thromboprophylaxis.

BACKGROUND: Blood coagulation abnormalities play a major role in COVID-19 pathophysiology. However, the specific details of hypercoagulation and anticoagulation treatment require investigation. The aim of this study was to investigate the status of the coagulation system by means of integral and local clotting assays in COVID-19 patients on admission to the hospital and in hospitalized COVID-19 patients receiving heparin thromboprophylaxis. METHODS: Thrombodynamics (TD), thromboelastography (TEG), and standard clotting assays were performed in 153 COVID-19 patients observed in a hospital setting. All patients receiving treatment, except extracorporeal membrane oxygenation (ECMO) patients (n = 108), were administered therapeutic doses of low molecular weight heparin (LMWH) depending on body weight. The ECMO patients (n = 15) were administered unfractionated heparin (UFH). RESULTS: On admission, the patients (n = 30) had extreme hypercoagulation by all integral assays: TD showed hypercoagulation in ~75% of patients, while TEG showed hypercoagulation in ~50% of patients. The patients receiving treatment showed a significant heparin response based on TD; 77% of measurements were in the hypocoagulation range, 15% were normal, and 8% remained in hypercoagulation. TEG showed less of a response to heparin: 24% of measurements were in the hypocoagulation range, 59% were normal and 17% remained in hypercoagulation. While hypocoagulation is likely due to heparin treatment, remaining in significant hypercoagulation may indicate insufficient anticoagulation for some patients, which is in agreement with our clinical findings. There were 3 study patients with registered thrombosis episodes, and all were outside the target range for TD parameters typical for effective thromboprophylaxis (1 patient was in weak hypocoagulation, atypical for the LMWH dose used, and 2 patients remained in the hypercoagulation range despite therapeutic LMWH doses). CONCLUSION: Patients with COVID-19 have severe hypercoagulation, which persists in some patients receiving anticoagulation treatment, while significant hypocoagulation is observed in others. The data suggest critical issues of hemostasis balance in these patients and indicate the potential importance of integral assays in its control.

Lymphocytes, Mean Platelet Volume, and Albumin in Critically Ill COVID-19 Patients with Venous Thromboembolism.

As one of the frequent complications leading to poor prognosis in hospitalized COVID-19 patients, a better understanding of venous thromboembolism (VTE) in COVID-19 patients is needed. We conducted a single-center, retrospective study on 96 COVID-19 patients admitted to the intensive care unit (ICU) from April to June 2022, in Shanghai Renji Hospital. Records of these COVID-19 patients upon admission were reviewed for demographic information, co-morbidities, vaccinations, treatment, and laboratory tests. VTE occurred in 11 (11.5%) cases among 96 COVID-19 patients despite the standard thromboprophylaxis since ICU admission. In COVID-VTE patients, a significant increase in B cells and a decrease in Ts cells were observed and a strong negative correlation (r = -0.9524, P = .0003) was found between these two populations. In COVID-19 patients with VTE, increased MPV and decreased albumin levels were seen in addition to the common VTE indicators of D-dimer abnormalities. The altered lymphocyte composition in COVID-VTE patients is noteworthy. In addition to D-dimer, MPV and albumin levels might be novel indicators for the risk of VTE in COVID-19 patients.

Major cardiovascular events after COVID-19, event rates post-vaccination, antiviral or anti-inflammatory therapy, and temporal trends: Rationale and methodology of the CORONA-VTE-Network study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with excess risk of cardiovascular and thrombotic events in the early post-infection period and during convalescence. Despite the progress in our understanding of cardiovascular complications, uncertainty persists with respect to more recent event rates, temporal trends, association between vaccination status and outcomes, and findings within vulnerable subgroups such as older adults (aged 65 years or older), or those undergoing hemodialysis. Sex-informed findings, including results among pregnant and breastfeeding women, as well as adjusted comparisons between male and female adults are similarly understudied. METHODS: Adult patients, aged ≥18 years, with polymerase chain reaction-confirmed COVID-19 who received inpatient or outpatient care at the participating centers of the registry are eligible for inclusion. A total of 10,000 patients have been included in this multicenter study, with Brigham and Women's Hospital (Boston, MA) serving as the coordinating center. Other sites include Beth Israel Deaconess Medical Center, Anne Arundel Medical Center, University of Virginia Medical Center, University of Colorado Health System, and Thomas Jefferson University Health System. Data elements will be ascertained manually for accuracy. The two main outcomes are 1) a composite of venous or arterial thrombotic events, and 2) a composite of major cardiovascular events, defined as venous or arterial thrombosis, myocarditis or heart failure with inpatient treatment, new atrial fibrillation/flutter, or cardiovascular death. Clinical outcomes are adjudicated by independent physicians. Vaccination status and time of inclusion in the study will be ascertained for subgroup-specific analyses. Outcomes are pre-specified to be reported separately for hospitalized patients versus those who were initially receiving outpatient care. Outcomes will be reported at 30-day and 90-day follow-up. Data cleaning at the sites and the data coordinating center and outcomes adjudication process are in-progress. CONCLUSIONS: The CORONA-VTE-Network study will share contemporary information related to rates of cardiovascular and thrombotic events in patients with COVID-19 overall, as well as within key subgroups, including by time of inclusion, vaccination status, patients undergoing hemodialysis, the elderly, and sex-informed analyses such as comparison of women and men, or among pregnant and breastfeeding women.

D-Dimer: An International Assessment of the Quality of Laboratory Testing: Implications for D-Dimer Use in the Real World (preprint)

Background: D-dimer assessment has an established role in the exclusion of venous thromboembolism (VTE) in symptomatic outpatients. It is also used in diagnosing disseminated intravascular coagulation (DIC), and more recently in the risk stratification of illness severity in COVID-19. D-dimer assays are neither standardized nor harmonized, use varying methodologies, and different reporting units, resulting in a potential lack of interchangeability between assay results.Objectives: Using large multi-year datasets from an international laboratory quality assurance program, we assessed: (1) common D-Dimer assays in use worldwide (2) differences in analytical performance between different methods and (3) inter-laboratory variability between positive samples.Methods: External proficiency testing results from laboratories participating in the External quality Control for Assays and Tests (ECAT) Foundation were analyzed from 2017 to 2020.Results: Annually, between 578 and 640 laboratories participated in the D-dimer sample surveys. The three commonest assays in use in the last survey of 2020 were the Siemens Innovance D-dimer (42%), the IL HemosIL D-dimer HS 500 (16%), and the Stago Liatest D-dimer Plus (11%) - all automated, quantitative, latex immunoassays expressed in Fibrinogen Equivalent Units (FEU). The highest inter-laboratory variability on the same samples was observed around the typical VTE exclusion threshold of 0.5 mg/L FEU. Lower inter-laboratory variability was observed at values above 0.7 mg/L FEU.Conclusions: Our study provides recent, international performance data on currently used D-Dimer assays and describes the significant variability between assays and across concentrations. We demonstrate that assays are not interchangeable, and using them interchangeably has the potential to result in clinically important errors. There is an urgent need to educate users about this issue and to work towards harmonization of D-dimer results and reporting units.

Thrombosis Occurrence in COVID-19 Compared With Other Infectious Causes of ARDS: A Contemporary Cohort.

Thrombosis occurrence in coronavirus disease 2019 (COVID-19) has been mostly compared to historical cohorts of patients with other respiratory infections. We retrospectively evaluated the thrombotic events that occurred in a contemporary cohort of patients hospitalized between March and July 2020 for acute respiratory distress syndrome (ARDS) according to the Berlin Definition and compared those with positive and negative real-time polymerase chain reaction results for wild-type severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using descriptive analysis. The association between COVID-19 and thrombotic risk was evaluated using logistic regression. 264 COVID-19-positive (56.8% male, 59.0 years [IQR 48.6-69.7], Padua score on admission 3.0 [2.0-3.0]) and 88 COVID-19-negative patients (58.0% male, 63.7 years [51.2-73.5], Padua score 3.0 [2.0-5.0]) were included. 10.2% of non-COVID-19 and 8.7% of COVID-19 patients presented ≥ 1 clinically relevant thrombotic event confirmed by imaging exam. After adjustment for sex, Padua score, intensive care unit stay, thromboprophylaxis, and hospitalization length, the odds ratio for thrombosis in COVID-19 was 0.69 (95% CI, 0.30-1.64). We, therefore, conclude that infection-induced ARDS carries an inherent thrombotic risk, which was comparable between patients with COVID-19 and other respiratory infections in our contemporary cohort.

Improving guideline-concordant thromboprophylaxis prescribing for children admitted to hospital with COVID-19.

BACKGROUND: The incidence of venous thrombo-embolism (VTE) in hospitalized children has increased by 130%-200% over the last two decades. Given this increase, many centers utilize electronic clinical decision support (CDS) to prognosticate VTE risk and recommend prophylaxis. SARS-CoV-2 infection (COVID-19) is a risk factor for VTE; however, CDS developed before the COVID-19 pandemic may not accurately prognosticate VTE risk in children with COVID-19. This study's objective was to identify areas to improve thromboprophylaxis recommendations for children with COVID-19. METHODS: Inpatients with a positive COVID-19 test at admission were identified at a quaternary-care pediatric center between March 1, 2020 and January 20, 2022. The results of the institution's automated CDS thromboprophylaxis recommendations were compared to institutional COVID-19 thromboprophylaxis guidelines and to the actual thromboprophylaxis received. CDS optimization was performed to improve adherence to COVID-19 thromboprophylaxis recommendations. RESULTS: Of the 329 patients included in this study, 106 (28.2%) were prescribed pharmaco-prophylaxis, 167 (50.8%) were identified by the institutional COVID-19 guidelines as requiring pharmaco-prophylaxis, and 45 (13.2%) were identified by the CDS as needing pharmaco-prophylaxis. On univariate analysis, only age 12 years or more was associated with recipient of appropriate prophylaxis (OR 1.78, 95% CI: 1.13-2.82, p = .013). Five patients developed VTEs; three had symptoms at presentation, two were identified as high risk for VTE by both the automated and best practice assessments but were not prescribed pharmaco-prophylaxis. CONCLUSION: Automated thromboprophylaxis recommendations developed prior to the COVID-19 pandemic may not identify all COVID-19 patients needing pharmaco-prophylaxis. Existing CDS tools need to be updated to reflect COVID-19-specific risk factors for VTEs.

Thrombotic events following the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) in Aotearoa New Zealand: A self-controlled case series study.

BACKGROUND: An association between thrombotic events and SARS-CoV-2 infection and the adenovirus-based COVID-19 vaccines has been established, leading to concern over the risk of thrombosis after BNT162b2 COVID-19 vaccination. OBJECTIVES: To evaluate the risk of arterial thrombosis, cerebral venous thrombosis (CVT), splanchnic thrombosis, and venous thromboembolism (VTE) following BNT162b2 vaccination in New Zealand. METHODS: This was a self-controlled case series using national hospitalisation and immunisation records to calculate incidence rate ratios (IRR). The study population included individuals aged ≥12 years, unvaccinated, or vaccinated with BNT162b2, who were hospitalised with one of the thrombotic events of interest from 19 February 2021 through 19 February 2022. The risk period was 0-21 days after receiving a primary or booster dose of BNT162b2. RESULTS: 6039 individuals were hospitalised with one of the thrombotic events examined, including 5127 with VTE, 605 with arterial thrombosis, 272 with splanchnic thrombosis, and 35 with CVT. The proportion of individuals vaccinated with at least one dose of BNT162b2 ranged from 82.7 % to 91.4 %. Compared with the control unexposed period, the IRR (95 % CI) of VTE, arterial thrombosis, splanchnic thrombosis, and CVT were 0.87 (0.76-1.00), 0.73 (0.56-0.95), 0.71 (0.43-1.16), and 0.87 (0.31-2.50) in the 21 days after BNT162b2 vaccination, respectively. There was no statistically significant increased risk of thrombosis following BNT162b2 in different ethnic groups in New Zealand. CONCLUSION: The BNT162b2 vaccine was not found to be associated with thrombosis in the general population or different ethnic groups in New Zealand, providing reassurance for the safety of the BNT162b2 vaccine.

Acute pulmonary embolism in times of SARS-CoV-2: Diagnostic and therapeutic management / Tromboembolismo pulmonar agudo en tiempos de SARS-CoV-2: diagnóstico y tratamiento

There is a clear association between novel coronavirus 2 infection and the diagnosis of venous thromboembolic disease, as a cosequence of the development of a systemic inflammatory response syndrome due to the activation of the coagulation cascade. It occurs in 90% of patients with severe forms of the infection, evidencing the presence of pulmonary endovascular micro and macro thrombosis. This suggests a possible clinical benefit of thromboprophylaxis according to the patient's clinical risk. The suspicion of venous thromboembolic disease in the context of this pandemic represents a diagnostic challenge due to the co-existence of similarities between both conditions in several different aspects. It should be noted that the diagnosis of acute pulmonary embolism does not exclude the possibility of simultaneous viral infection. The evaluation of patients with suspected acute pulmonary embolism in the context of the pandemic should be optimized in order to implement a rapid diagnosis and treatment to reduce the associated morbidity and mortality. This will help reducing infectious risk for health-care professionals and other patients.

Existe una clara relación entre la infección por el nuevo coronavirus 2 y el diagnóstico de enfermedad tromboembólica venosa, como consecuencia del desarrollo de un síndrome de respuesta inflamatoria sistémica debido a la activación de la cascada de la coagulación. Se presenta en el 90% de los pacientes con formas graves de la infección, lo que revela la presencia de microtrombosis y macrotrombosis intravascular pulmonar. Esto sugiere un posible beneficio clínico de la aplicación de una tromboprofilaxis adecuada al riesgo clínico de cada paciente. Asimismo, la sospecha de enfermedad tromboembólica venosa en el contexto de esta pandemia representa un reto diagnóstico debido a la existencia de similitudes entre ambas alteraciones en varios aspectos. Debe tenerse en cuenta que el diagnóstico de tromboembolismo pulmonar agudo no excluye la posibilidad de infección viral. La valoración de pacientes con sospecha de tromboembolismo pulmonar agudo en el contexto de la pandemia debe ser eficaz para establecer un diagnóstico y tratamiento con rapidez, a fin de reducir la morbilidad y mortalidad adjuntas, sin que ello eleve el riesgo de infección para los profesionales de la salud y otros pacientes.

Guidelines for prophylaxis and anti-thrombotic treatment for patients with COVID-19. Consensus of the Latin American Cooperative Group on Hemostasis and Thrombosis (CLAHT) / Guía de profilaxia y tratamiento antitrombótico para pacientes con COVID-19. Consenso del Grupo Cooperativo Latinoamericano en Hemostasia y Trombosis (CLAHT)

Coagulopathy and thrombosis associated with coronavirus disease 2019 (COVID-19) represent a major issue in the management of this disease. In the past months, clinical studies have demonstrated that COVID-19 patients present with a particular hypercoagulable state, in which a markedly increased D-dimer concomitant with increased levels of fibrinogen are observed. This hypercoagulable state leads to an increased risk of thrombosis, which seems to be higher among those patients with critical symptoms of COVID-19. The best therapeutic approach to prevent thrombotic events in COVID-19 has not been determined yet and several questions regarding thromboprophylaxis therapy, such as the time to initiate anticoagulation, type of anticoagulant and dose regimen, have emerged among physicians. To address these concerns, several medical societies have published position papers to provide the opinion of thrombosis experts on the management of coagulopathy and thrombosis associated with COVID-19. In line with this, the Latin America Cooperative Group of Hemostasis and Thrombosis (Grupo CLAHT) has constituted a panel of experts in thrombosis and hemostasis to discuss the available data on this topic. The aim of this review is to summarize the current evidence regarding hemostatic impairment and thrombotic risk in COVID-19 and to provide a carefully revised opinion of Latin American experts on the thromboprophylaxis and management of thrombotic events and coagulopathy in patients with suspected COVID-19.

La coagulopatía y la trombosis asociadas a la enfermedad por coronavirus 2019 (COVID-19) representan un problema importante en el manejo de esta enfermedad. Los estudios clínicos de los últimos meses han demostrado que los pacientes con COVID-19 presentan un estado de hipercoagulabilidad particular, en el que se observa un aumento notable del dímero D concomitante con niveles elevados de fibrinógeno. El estado de hipercoagulabilidad conduce a un mayor riesgo de trombosis, que parece ser mayor entre aquellos pacientes con síntomas críticos de COVID-19. El mejor enfoque terapéutico para prevenir los eventos trombóticos en esta nueva enfermedad aún no se ha determinado y han surgido varias preguntas con respecto a la tromboprofilaxia, como el momento adecuado para iniciar la anticoagulación, el tipo de anticoagulante y el régimen de dosis. Para abordar estas preocupaciones, varias sociedades médicas han publicado artículos de posición para brindar la opinión de expertos en trombosis sobre el manejo de la coagulopatía y trombosis asociadas a COVID-19. Grupo Cooperativo Latinoamericano de Hemostasia y Trombosis (Grupo CLAHT) ha convocado a un panel de expertos en trombosis y hemostasia para discutir los datos disponibles sobre este tema. El objetivo de esta revisión es resumir la evidencia actual con respecto al deterioro hemostático y el riesgo trombótico en el COVID-19 y proporcionar una opinión cuidadosamente revisada de los expertos latinoamericanos sobre la tromboprofilaxis y el manejo de eventos trombóticos y coagulopatía en pacientes con sospecha de COVID-19.

COVID in obstetrics: labor analgesia and cesarean section.

PURPOSE OF REVIEW: This review is based on the latest evidence to provide a good standard of care for COVID-19 parturients and protection to healthcare givers. RECENT FINDINGS: COVID-19 by itself is not an indication for cesarean section. Different publications demonstrated the efficacy of neuraxial analgesia/anesthesia for delivery. Although SARS-CoV-2 was associated with a certain neurotropism, neuraxial block was not associated with neurological damage in COVID-19 parturients, and seems as safe and effective as in normal situations. It permits to avoid a general anesthesia in case of intrapartum cesarean section. Epidural failure is a concern: it may lead to a general anesthesia in case of emergency cesarean section. Local protocols and well-trained anesthesiologists will be helpful. COVID-19 patients require special circuits and every step (transfer to and from theatre, recovery, analgesia, and so on) should be planned in advance. For cesarean section under general anesthesia, personal protection equipment must be enhanced. Postoperative analgesia with neuraxial opioids, NSAIDs, or regional blocks are recommended. COVID-19 and pregnancy increase the risk of thrombosis, so thromboprophylaxis has to be considered and protocolized. SUMMARY: Anesthetic care for delivery in COVID-19 parturients should include neuraxial blocks. Special attention should be paid on the risk of thrombosis.

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19.

INTRODUCTION: Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU). METHODS: In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia. RESULTS: Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00-8.08, p = 0.050; HR = 3.87, 95% CI = 1.12-13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively. CONCLUSION: VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.