Outcomes in patients discharged with extended venous thromboembolism prophylaxis after hospitalization with COVID-19.

BACKGROUND: Venous thromboembolism (VTE) is a known complication of coronavirus disease (COVID-19) in patients requiring hospitalization and intensive care. We examined the association between extended pharmacological VTE prophylaxis and outcomes among patients hospitalized with COVID-19. METHODS: This was a retrospective cohort study of patients with an index positive SARS-CoV-2 polymerase chain reaction (PCR) test at the time of, or during hospitalization. Patients who were prescribed extended pharmacological VTE prophylaxis were compared against patients who were not. Multivariable logistic regression was used to produce odds ratio (OR) estimates and Cox proportional hazard models for hazard ratios (HR) with 95% CI to examine the association between pharmacological VTE prophylaxis and outcomes of interest. Primary outcomes were 30- and 90-day VTE events. Secondary outcomes included 30- and 90-day mortality, 30-day superficial venous thrombosis (SVT), acute myocardial infarction (MI), acute ischemic stroke, critical limb ischemia, clinically significant bleeding, and inpatient readmissions. RESULTS: A total of 1936 patients were included in the study. Among them, 731 (38%) were discharged on extended pharmacological VTE prophylaxis. No significant difference was found in 30- and 90-day VTE events among groups. Patients discharged on extended VTE prophylaxis showed improved survival at 30 (HR: 0.35; 95% CI: 0.21-0.59) and 90 days (HR: 0.36; 95% CI: 0.23-0.55) and reduced inpatient readmission at 30 days (OR: 0.12; 95% CI: 0.04-0.33) when compared to those without. CONCLUSION: Patients discharged on extended VTE prophylaxis after hospitalization due to COVID-19 had similar thrombotic events on follow-up. However, use of extended VTE prophylaxis was associated with improved 30- and 90-day survival and reduced risk of 30-day inpatient readmission.

Clinically stable covid-19 patients presenting to acute unscheduled episodic care venues have increased risk of hospitalization: secondary analysis of a randomized control trial.

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial. METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive patients).We report the primary composite outcome of cardiopulmonary hospitalizations, symptomatic venous thromboembolism, myocardial infarction, stroke, transient ischemic attack, systemic arterial thromboembolism, or death among stable outpatients stratified by enrollment setting, AUEC versus MC. A propensity score for AUEC enrollment was created, and Cox proportional hazards regression with inverse probability weighting (IPW) was used to compare the primary outcome by enrollment location. RESULTS: Among the 657 ACTIV-4B patients randomized, 533 (81.1%) with known enrollment setting data were included in this analysis, 227 from AUEC settings and 306 from MC settings. In a multivariate logistic regression model, time from COVID test, age, Black race, Hispanic ethnicity, and body mass index were associated with AUEC enrollment. Irrespective of trial treatment allocation, patients enrolled at an AUEC setting were 10-times more likely to suffer from the adjudicated primary outcome, 7.9% vs. 0.7%; p < 0.001, compared with patients enrolled at a MC setting. Upon Cox regression analysis adjustment patients enrolled at an AUEC setting remained at significant risk of the primary composite outcome, HR 3.40 (95% CI 1.46, 7.94). CONCLUSIONS: Patients with clinically stable COVID-19 presenting to an AUEC enrollment setting represent a population at increased risk of arterial and venous thrombosis complications, hospitalization for cardiopulmonary events, or death, when adjusted for other risk factors, compared with patients enrolled at a MC setting. Future outpatient therapeutic trials and clinical therapeutic delivery programs of clinically stable COVID-19 patients may focus on inclusion of higher-risk patient populations from AUEC engagement locations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498273.

COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry.

INTRODUCTION: Hypercoagulable state contributing to thrombotic complications worsens COVID-19 severity and outcomes, while anticoagulation improves outcomes by alleviating hypercoagulability. OBJECTIVES: Examine whether hemophilia, an inherent hypocoagulable condition, offers protection against COVID-19 severity and reduces VTE risk in persons with hemophilia (PwH). PATIENTS/METHODS: A 1: 3 propensity score (PS) matched retrospective cohort study used national COVID-19 registry data (January 2020 through January 2022) to compare outcomes between 300 male PwH and 900 matched controls without hemophilia. RESULTS: Analyses of PwH demonstrated known risk-factors (older age, heart failure, hypertension, cancer/malignancy, dementia, renal and liver disease) contributed to severe COVID-19 and/or 30-day-all-cause mortality. Non-CNS bleeding was an additional risk-factor for poor outcomes in PwH. Odds of developing VTE with COVID-19 in PwH were associated with pre-COVID VTE diagnosis (OR 51.9, 95% CI 12.8-266, p<0.001), anticoagulation therapy (OR 12.7, 95% CI 3.01-48.6, p<0.001) and pulmonary disease (OR 16.1, 95% CI 10.4-25.4, p<0.001). Thirty-day-all-cause-mortality (OR 1.27, 95% CI 0.75-2.11, p=0.3), and VTE events (OR 1.32, 95% CI 0.64-2.73, p=0.4) were not significantly different between matched cohorts; however, hospitalizations (OR 1.58, 95% CI 1.20-2.10, p 0.001) and non-CNS bleeding events (OR 4.78, 95% CI 2.98-7.48, p<0.001) were increased in PwH. In multivariate analyses, hemophilia did not reduce adverse outcomes (OR 1.32, 95% CI 0.74-2.31, p 0.2) nor VTE (OR 1.14; 95% CI 0.44-2.67, p 0.8) but increased bleeding risk (OR 4.70, 95% CI 2.98-7.48, p<0.001). CONCLUSION: After adjusting for patient characteristics/comorbidities, hemophilia increased bleeding risk with COVID-19 but did not protect against severe disease and VTE.

Has Lockdown and COVID-19 Led to a Change in the Characteristics of Deep Vein Thrombosis and Patients Who Are Afflicted With It?

BACKGROUND: There is growing evidence identifying coronavirus disease 2019 (COVID-19) as a significant risk factor for thrombosis in inpatients. However, it remains uncertain if patients in the community have been influenced during the COVID-19 pandemic and national lockdown. This study, across four centres in the United Kingdom (UK), reviewed outpatients with deep vein thrombosis (DVT). AIM: This study aims to find out whether lockdown and COVID-19 led to a change in the characteristics of DVT and patients who are afflicted with it, alongside a review of DVT service. METHODS: Data was collected retrospectively from electronic patient records system for the following periods: April 1 to June 30, 2019, and April 1 to June 30, 2020. These were the key months during the first national lockdown in UK. Data were analysed for patient demographics, risk factors, characteristics of DVT, management, and DVT reoccurrence. Statistical analyses were performed using GraphPad Prism 8 (Dotmatics, Boston, Massachusetts, United States). RESULTS: During the study periods, 227 outpatients from the community sustained DVT in 2019 and 211 in 2020. Of these patients, 13 in 2020 were COVID-19 positive. There was a difference in gender distribution with 128 males and 99 females in 2019, and 93 males and 118 females in 2020 (p= 0.0128). No significant difference was noted in the incidence of thrombophilia with nine in 2019 and three in 2020 (p=0.1437). Fewer long-haul journeys were made in 2020 (only two), compared to 16 in 2019 (p=0.012). Fewer patients had immobility as a risk factor in 2020 (n=55) compared to 2019 (n=79) (p=0.0494). However, there were more patients using oral contraceptive pills, with one in 2019 and nine in 2020 (p=0.0086) . CONCLUSION: There is no significant difference in the characteristics, extent, and management of DVT prior to and during the COVID-19 lockdown. National lockdowns do not affect DVT in the community; however, it is important to highlight the surrounding inpatient numbers.

Elective Joint Arthroplasty Should be Delayed by One Month After COVID-19 Infection to Prevent Postoperative Complications.

BACKGROUND: It remains unclear whether a history of recent COVID-19 infection affects the outcomes and risks of complications of total joint arthroplasty (TJA). The purpose of this study was to compare the outcomes of TJA in patients who have and have not had a recent COVID-19 infection. METHODS: A large national database was queried for patients undergoing total hip and total knee arthroplasty. Patients who had a diagnosis of COVID-19 within 90-days preoperatively were matched to patients who did not have a history of COVID-19 based on age, sex, Charlson Comorbidity Index, and procedure. A total of 31,453 patients undergoing TJA were identified, of which 616 (2.0%) had a preoperative diagnosis of COVID-19. Of these, 281 COVID-19 positive patients were matched with 281 patients who did not have COVID-19. The 90-day complications were compared between patients who did and did not have a diagnosis of COVID-19 at 1, 2, and 3 months preoperatively. Multivariate analyses were used to further control for potential confounders. RESULTS: Multivariate analysis of the matched cohorts showed that COVID-19 infection within 1 month prior to TJA was associated with an increased rate of postoperative deep vein thrombosis (odds ratio [OR]: 6.50, 95% confidence interval: 1.48-28.45, P = .010) and venous thromboembolic events (odds ratio: 8.32, confidence interval: 2.12-34.84, P = .002). COVID-19 infection within 2 and 3 months prior to TJA did not significantly affect outcomes. CONCLUSION: COVID-19 infection within 1 month prior to TJA significantly increases the risk of postoperative thromboembolic events; however, complication rates returned to baseline after that time point. Surgeons should consider delaying elective total hip arthroplasty and total knee arthroplasty until 1 month after a COVID-19 infection.

Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19. METHODS: We performed a retrospective multicenter case-control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020. RESULTS: A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30) = 0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC] = 0.55, 95% CI: 0.44-0.65, P value = .32; alpha angle [α] AUC = 0.58, 95% CI: 0.47-0.69, P value = .17; K time AUC = 0.58, 95% CI: 0.46-0.69, P value = .67; maximum amplitude (MA) AUC = 0.54, 95% CI: 0.44-0.64, P value = .47; reaction time [R time] AUC = 0.53, 95% CI: 0.42-0.65, P value = .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC = 0.51, 95% CI: 0.42-0.60, P value = .84; R time AUC = 0.57, 95%CI: 0.48-0.67, P value .07; α AUC = 0.59, 95%CI: 0.51-0.68, P value = .02; K time AUC = 0.62, 95% CI: 0.53-0.70, P value = .07; MA AUC = 0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events. CONCLUSIONS: In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.

Venous thromboembolism in viral diseases: A comprehensive literature review.

Venous thromboembolism (VTE) is known to be a common respiratory and/or cardiovascular complication in hospitalized patients with viral infections. Numerous studies have proven human immunodeficiency virus infection to be a prothrombotic condition. An elevated VTE risk has been observed in critically ill H1N1 influenza patients. VTE risk is remarkably higher in patients infected with the Hepatitis C virus in contrast to uninfected subjects. The elevation of D-dimer levels supported the association between Chikungunya and the Zika virus and the rise of clinical VTE risk. Varicella-zoster virus is a risk factor for both cellulitis and the consequent invasive bacterial disease which may take part in thrombotic initiation. Eventually, hospitalized patients infected with the coronavirus disease of 2019 (COVID-19), the cause of the ongoing worldwide pandemic, could mainly suffer from an anomalous risk of coagulation activation with enhanced venous thrombosis events and poor quality clinical course. Although the risk of VTE in nonhospitalized COVID-19 patients is not known yet, there are a large number of guidelines and studies on thromboprophylaxis administration for COVID-19 cases. This study aims to take a detailed look at the effect of viral diseases on VTE, the epidemiology of VTE in viral diseases, and the diagnosis and treatment of VTE.

Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Cross-immunity against SARS-COV-2 variants of concern in naturally infected critically ill COVID-19 patients.

Critically ill patients infected with SARS-CoV-2 display adaptive immunity, but it is unknown if they develop cross-reactivity to variants of concern (VOCs). We profiled cross-immunity against SARS-CoV-2 VOCs in naturally infected, non-vaccinated, critically ill COVID-19 patients. Wave-1 patients (wild-type infection) were similar in demographics to Wave-3 patients (wild-type/alpha infection), but Wave-3 patients had higher illness severity. Wave-1 patients developed increasing neutralizing antibodies to all variants, as did patients during Wave-3. Wave-3 patients, when compared to Wave-1, developed more robust antibody responses, particularly for wild-type, alpha, beta and delta variants. Within Wave-3, neutralizing antibodies were significantly less to beta and gamma VOCs, as compared to wild-type, alpha and delta. Patients previously diagnosed with cancer or chronic obstructive pulmonary disease had significantly fewer neutralizing antibodies. Naturally infected ICU patients developed adaptive responses to all VOCs, with greater responses in those patients more likely to be infected with the alpha variant, versus wild-type.

Venous thromboembolism in hospitalized patients with COVID-19

Background: The aim of the study was to analyze the results of treatment and the factors of risk of mortality among the patients with COVID-19 and venous thromboembolism (VTE). Method(s): Retrospective analysis of 87 patients with COVID-19 and VTE treated fromApril 2020 to March 2021 in the City HospitalNo40 of Yekaterinburg was performed. Demographic, clinical and laboratory data, including duplex ultrasound, multispiral CT pulmonary angiograms, Charlson index were retrieved. Comparisons were made between two groups: Survivors (n=39) and deceased (n=48). Statistical processing was performed using EZR v. 4.1.2. Result(s): Among 87 patients hospitalized with COVID- 19 (average age - 68 years, 48(55,2%) women) intensive care was required for 61(70,1%) patients. Duplex ultrasound showed 74 deep vein thrombosis (DVT);53(71,6%) - distal DVT, 13(17,6%) - femoropopliteal DVT, 1(1,3%) - iliofemoral DVT, 3(4,1%) - surface veins of extremities, 3(4,1%) - inferior vena cava, 1(1,3%) - right heart chambers. Bilateral lower extremity DVT developed in 29(39,7%) patients. Isolated venous thrombosis was observed in 47(54,1%) patients. 27(31,0%) patients with venous thrombosis had pulmonary embolism (PE), in 13(14,9%) patients with PE the source was not found. In 17(23%) cases DVT had free flotation. Before the identification of VTE, all patients were receiving direct anticoagulants: Prophylactic doses - 31(35,6%), intermediate doses - 33(37,9%), therapeutic doses - 23(26,4%). Deceased patients were older than survivors (average age - 71,0 years (IQR 61,0;81,2);r=0,012). Severe COVID-19, requirement of intensive therapy and mechanical lung ventilation prevailed in the group of deceased (p<0,001). Charlson index was higher in the group of deceased (6,0 (IQR 4,0;6,2) vs 4,0 (IQR 2,0;5,0);p=0,007). The index of 5 points and more showed that the probability of death increased by 3 times (OR 2,98, 95% SI 1,2-7,1;p=0,01). In the structure of VTE in the group of deceased, DVT was mainly in combination with PE of 20(47,1%);p=0,027. In both groups, distal DVT was more frequent: 21(61,8%) among the survivors, 32(80,0%) among the deceased. The localization of venous thrombosis, flotation, bilateral DVT of the lower extremities were not statistically different in the studied groups. Laboratory indicators: D-dimer (3955.0 ng/ml (IQR 2550,0;5325,0) - survivors, 4600,0 ng/ml (IQR 2745,0;38300,0) - deceased;p=0,291);hyperfibrinogenemy (5,2 g/l (IQR 4,0;6,5) - deceased;r=0,033). The dose of direct anticoagulants before the identification VTE was not statistically significant. Conclusion(s): The factors of unfavorable outcome in patients of COVID-19 and VTE were: Age, Charlson index higher than 4 points, intensive therapy, mechanical lung ventilation, DVT in combination with PE. The dose of direct anticoagulants before to the detection of VTE did not affect the unfavorable outcome in the studied category of patients.

Efficacy of different anticoagulant doses for patients with COVID-19: a systematic review and network meta-analysis.

PURPOSE: As no reported randomized control trials (RCTs) directly compare the three administration doses of anticoagulants (prophylactic dose, treatment dose, and no treatment), the most recommended dose to be administered to patients with coronavirus disease 2019 (COVID-19) remains unclear. The purpose of this study was to examine the effects of anticoagulant doses administered to patients with COVID-19, using a network meta-analysis (NMA) including high-quality studies. METHODS: All eligible trials from the Cochrane Central Register of Controlled Trials, MEDLINE, and Clinicaltrials.gov were included. We included RCTs and observational studies adjusted for covariates for patients aged ≥ 18 years and hospitalized due to objectively confirmed COVID-19. The main study outcome was mortality. RESULTS: In patients with moderate COVID-19, the prophylactic (relative risk (RR) 0.64 [95% confidence interval (CI) 0.52-0.80]) and treatment dose (RR 0.57 [95% CI 0.45-0.72] were associated with a lower risk of short-term mortality than that with no anticoagulant treatment. However, the prophylactic and treatment dose groups were not significantly different. The hierarchy for efficacy in reducing short-term mortality was treatment dose (P score 92.4) > prophylactic dose (57.6) > no treatment (0.0). In patients with severe COVID-19, due to the absence of trials with the no-treatment group, NMA could not be conducted. However, pairwise comparison did not show a significant difference between the prophylactic and treatment dose groups. CONCLUSIONS: Treatment and prophylactic doses of anticoagulants showed similar effects on mortality; however, the treatment dose is preferred over the prophylactic dose for patients with both moderate and severe COVID-19. TRIAL REGISTRATION NUMBER AND REGISTRATION DATES: PROSPERO (registration number: CRD42021245308, 05/21/2021).

Recurrent upper extremity arterial thrombosis preceding a diagnosis of COVID-19.

Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Introduction and purpose: Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. Methods: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. Results: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p = 0.003; 52 (34.4%) vs 35 (23.2%), p = 0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. Conclusions: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.

Antecedentes y objetivos: La fibrilación auricular (FA) es frecuente en pacientes ingresados por COVID-19 grave. Sin embargo, los datos sobre el manejo de la anticoagulación crónica en estos pacientes son escasos. Analizamos la anticoagulación y la incidencia de episodios cardiovasculares mayores en pacientes con FA ingresados por la COVID-19. Métodos: Retrospectivamente, se identificaron todos los pacientes con FA ingresados por la COVID-19 entre marzo y mayo de 2020, en 9 hospitales españoles. Se seleccionó un grupo control de pacientes ingresados consecutivamente por la COVID-19 sin FA. Se compararon las características basales, incidencia de hemorragias mayores, episodios trombóticos y mortalidad. Para reducir potenciales factores de confusión se realizó un emparejamiento por puntuación de propensión, así como un análisis multivariante para predecir hemorragia mayor y mortalidad. Resultados: Se incluyeron 305 pacientes con FA ingresados por la COVID-19. Tras el emparejamiento por puntuación de propensión, 151 pacientes con FA fueron emparejados con 151 controles. Durante el ingreso, la heparina de bajo peso molecular fue el principal anticoagulante y la incidencia de hemorragia mayor y mortalidad fue mayor en el grupo de FA (16[10,6%] vs. 3[2%], p = 0,003; 52[34,4%] vs. 35[23,2%], p = 0,03, respectivamente). El análisis multivariante demostró la presencia de FA como predictor independiente de sangrados y mortalidad intrahospitalaria en los pacientes con la COVID-19. En el grupo de FA, un segundo análisis multivariante identificó valores elevados de dímero-D como predictor independiente de hemorragia mayor intrahospitalaria. Conclusiones: Los pacientes con FA ingresados por la COVID-19 representan una población de alto riesgo de sangrado y mortalidad durante el ingreso. Parece recomendable individualizar la anticoagulación durante el ingreso, considerando el riesgo específico de sangrado y trombosis.

Venous thromboembolism in COVID-19: A meta-summary of cases.

OBJECTIVES: To summarize cases of venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) among coronavirus disease (COVID-19) patients and discuss their symptoms, diagnostic method, clinical features, and prognosis. METHODS: All major databases were searched for relevant studies published between December 1, 2019 and May 5, 2021. RESULTS: A total of 233 articles were identified, 22 describing 48 patients were included. A total of 79.1% had PE and 20.9% had DVT. Most patients were men, with a mean age of 56 years. Comorbidities were present in 70.8%, and 85.4% had at least one risk factor of VTE. 56.3% had received anticoagulation therapy. Most patients were treated in the general ward. Complications occurred in 27.1% of the patients, and recovery was achieved in 80.4%. CONCLUSION: Venous thromboembolism must be suspected even in patients who had received prior anticoagulant regimens or in stable cases, especially in males, the elderly, and patients with comorbidities and high D-dimer levels.

Assessment of the Effect on Thromboprophylaxis with Multifaceted Quality Improvement Intervention based on Clinical Decision Support System in Hospitalized Patients: A Pilot Study.

BACKGROUND: To explore the feasibility and effectiveness of multifaceted quality improvement intervention based on the clinical decision support system (CDSS) in VTE prophylaxis in hospitalized patients. METHODS: A randomized, department-based clinical trial was conducted in the department of respiratory and critical care medicine, orthopedic, and general surgery wards. Patients aged ≥18 years, without VTE in admission, were allocated to the intervention group and received regular care combined with multifaceted quality improvement intervention based on CDSS during hospitalization. VTE prophylaxis rate and the occurrence of hospital-associated VTE events were analyzed as primary and secondary outcomes. RESULTS: A total of 3644 eligible residents were enrolled in this trial. With the implementation of the multifaceted quality improvement intervention based on the CDSS, the VTE prophylaxis rate of the intervention group increased from 22.93% to 34.56% (p < 0.001), and the incidence of HA-VTE events increased from 0.49% to 1.00% (p = 0.366). In the nonintervention group, the VTE prophylaxis rate increased from 24.49% to 27.90% (p = 0.091), and the incidence of HA-VTE events increased from 0.47% to 2.02% (p = 0.001). CONCLUSIONS: Multifaceted quality improvement intervention based on the CDSS strategy is feasible and expected to facilitate implementation of the recommended VTE prophylaxis strategies and reduce the incidence of HA-VTE in hospital. However, it is necessary to conduct more multicenter clinical trials in the future to provide more reliable real-world evidence.

A systematic review of biomarkers among hospitalized patients with COVID-19 predictive of venous thromboembolism: A communication from the Predictive and Diagnostic Variables Scientific and Standardization Committee of the ISTH.

Background: Thrombosis is reported to occur more often among patients with COVID-19 than otherwise expected in the setting of viral pneumonia and sepsis. Systemic inflammatory biomarkers may be associated with venous thromboembolism (VTE) risk. The ISTH subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease aimed to report the evidence on prognostic biomarkers for VTE in hospitalized patients with COVID-19. Methods: Using a standardized Preferred Reporting Items for Systematic Reviews and Meta-analysis methodology, we conducted a systematic literature review to identify studies reporting prognostic biomarkers for VTE among hospitalized patients with COVID-19. Eligible studies included adults hospitalized with COVID-19 and reported the prognostic associations between any biomarker measured on admission, and the subsequent diagnosis of deep vein thrombosis or pulmonary embolism. Two authors reviewed titles and abstracts, and three authors extracted study data and performed review of bias. Results were displayed descriptively. Meta-analysis was not possible. Results: From the initial 196 identified studies, full-text review was performed for 72 studies. Admission D-dimer levels were associated with VTE during hospitalization in five studies, and elevated platelet count was associated with VTE during hospitalization in one study. The risk of bias ranged from low to high for included studies. Overall, there was a paucity of high-quality prognostic studies. Studies on other biomarkers did not meet the systematic review inclusion criteria. Conclusions: Admission D-dimer was associated with VTE diagnosis during hospitalization for COVID-19; however, prospective validation of this finding is needed to identify optimal D-dimer thresholds to guide VTE prophylaxis measures.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.