Thrombophilia, characterized by an imbalance between fibrinolysis and coagulation leading to inappropriate blood clotting, is a significant medical condition. The CDC has designated it as an underdiagnosed, serious, and potentially preventable disorder, contributing to an estimated 600,000-900,000 cases and 100,000 deaths annually in the United States. These figures surpass the combined annual mortality of AIDS, breast cancer, and motor vehicle accidents. The pathogenesis of thrombophilia involves complex interactions between genetic predispositions, such as mutations in Factor V Leiden, Factor II, MTHFR, and Serpine-1, and environmental factors, including unhealthy lifestyles, prolonged hospitalization, obesity, and cancer. Prevalence of specific genetic mutations varies across populations. Additional risk factors include age, family history, and pregnancy, with recent attention to increased susceptibility in SARS-CoV-2 infection. While molecular diagnostic techniques are available, there remains a need for robust, cost-effective, and accurate screening methods for large populations. This systematic review provides an updated overview of thrombophilia, encompassing pathophysiology, epidemiology, genetic and environmental risk factors, coagulation cascade, population-specific mutation prevalence, and diagnostic approaches. By synthesizing clinical and molecular evidence, this review aims to guide researchers, hematologists, and clinicians in the diagnosis and management of thrombophilia.

A subset of coronavirus disease 2019 (COVID-19) patients develops severe symptoms, characterized by acute lung injury, endothelial dysfunction and microthrombosis. Viral infection and immune cell activation contribute to this phenotype. It is known that systemic inflammation, evidenced by circulating inflammatory factors in patient plasma, is also likely to be involved in the pathophysiology of severe COVID-19. Here, we evaluate whether systemic inflammatory factors can induce endothelial dysfunction and subsequent thromboinflammation. We use a microfluidic Vessel-on-Chip model lined by human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs), stimulate it with plasma from hospitalized COVID-19 patients and perfuse it with human whole blood. COVID-19 plasma exhibited elevated levels of inflammatory cytokines compared to plasma from healthy controls. Incubation of hiPSC-ECs with COVID-19 plasma showed an activated endothelial phenotype, characterized by upregulation of inflammatory markers and transcriptomic patterns of host defense against viral infection. Treatment with COVID-19 plasma induced increased platelet aggregation in the Vessel-on-Chip, which was associated partially with formation of neutrophil extracellular traps (NETosis). Our study demonstrates that factors in the plasma play a causative role in thromboinflammation in the context of COVID-19. The presented Vessel-on-Chip can enable future studies on diagnosis, prevention and treatment of severe COVID-19.

The aim of the present study was to quantify the rate of thromboembolic events (TE) in pregnant women with SARS-CoV-2 infection and to characterize risk factors to provide a basis for individualized recommendation on prophylactic measures.

CRONOS is a multicenter, prospective observational study conducted in Germany and Austria during the COVID-19 pandemic. Pregnant women with confirmed SARS-CoV-2 infection were enrolled. Data on demographics, medical history, COVID-19-related aspects, and pregnancy and birth outcomes were collected. TE was particularly queried and used as the primary outcome. A combination of "TE," "maternal or fetal death," or "severe postpartum hemorrhage" was defined as a secondary endpoint. Risk analyses were performed using univariate and multivariable logistic regression models.

Data from 8033 pregnant patients showed 40 TEs (0.5% incidence). TE rates were 10% in ICU patients, 0.2-0.4% in those with moderate-to-mild COVID-19, and < 0.1% in asymptomatic women. Pulmonary embolism occurred in 21 cases, deep vein thrombosis in 12, and 7 had atypical or arterial TE. Risk factors included advanced gestational age, COVID-19 symptoms, hospitalization or ICU admission, premature birth, cesarean section, delivery within 4 weeks of infection, higher weight gain, anemia, and chronic inflammatory bowel disease. COVID-19 vaccination reduced risk. The logistic risk model yielded an AUC of 0.87 (95% CI 0.81-0.94).

The TE rate in pregnant women is largely determined by the severity of the disease. In asymptomatic or mild cases, other factors outweigh TE risk, while severe COVID-19 requiring ICU admission poses a high TE risk despite prophylaxis.

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.

COVID-19, caused by the SARS-CoV-2 virus, is not only characterized by respiratory symptoms but is also associated with a wide range of systemic complications, including significant hematologic abnormalities. This is a comprehensive review of the current literature, using PubMed and Google Scholar, on the pathophysiology and incidence of thromboembolic events in COVID-19 patients and thromboprophylaxis. COVID-19 infection induces a prothrombotic state in patients through the dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, elevated von Willebrand factor (vWF), and a dysregulated immune response involving the complement system and neutrophil extracellular traps (NETs). As a result, thromboembolic complications have emerged in COVID-19 cases, occurring more frequently in severe cases and hospitalized patients. These thrombotic events affect both venous and arterial circulation, with increased incidences of deep venous thrombosis (DVT), pulmonary embolism (PE), systemic arterial thrombosis, and myocardial infarction (MI). While DVT and PE are more common, the literature highlights the potential lethal consequences of arterial thromboembolism (ATE). This review also briefly examines the ongoing discussions regarding the use of anticoagulants for the prevention of thrombotic events in COVID-19 patients. While theoretically promising, current studies have yielded varied outcomes: Some suggest potential benefits, whereas others report an increased risk of bleeding events among hospitalized patients. Therefore, further large-scale studies are needed to assess the efficacy and safety of anticoagulants for thromboprophylaxis in COVID-19 patients.

Limited knowledge exists about prophylactic anticoagulation patterns in patients hospitalized for COVID-19.

We conducted a retrospective cohort study using American Heart Association COVID-19 Cardiovascular Disease Registry data from May 2020 to March 2022. We included patients without preexisting indications for or contraindications to anticoagulation, excluding those with missing anticoagulation data. Patients were categorized by the highest anticoagulation dose received. Multilevel logistic regression was used to assess the relationship between anticoagulation use/dose, patient demographics, clinical presentation, in-hospital course, institutional characteristics, and admission date, accounting for hospital clustering. Among 26 775 patients, 4157 (16%) received no anticoagulation, 15 617 (58%) low-dose, 3071 (11%) intermediate-dose, and 3930 (15%) full-dose anticoagulation. Significant hospital-level variability occurred for any anticoagulation use (range, 0%-98%; P<0.0001) and by dose (full anticoagulation range, 0%-85%; P<0.0001). Controlling for hospital variability, older age, male sex, non-White race, higher body mass index, higher platelets, corticosteroid use, and intensive care unit admission were positively associated with any anticoagulation use. Older age, male sex, higher body mass index, higher platelets, corticosteroid use, intensive care unit admission, mechanical ventilation, and admission before October 2020 were associated with higher anticoagulation dose (full versus low dose). Rates of no anticoagulation significantly increased in both intensive care unit and non-intensive care unit strata over time (P trend=0.01 and <0.0001, respectively).

In this large real-world analysis, nearly 1 in 6 patients hospitalized for COVID-19 received no prophylactic anticoagulation. Patient and disease characteristics associated with thrombotic risk and COVID-19 severity correlated with anticoagulation strategy. Importantly, substantial institutional differences emerged, highlighting gaps between clinical practice and guideline recommendations.

In some reports, antiphospholipid antibodies (aPL) prevalence is higher in COVID-19 patients. This study intended to compare aPL prevalence between COVID-19 patients and healthy controls, and differences in aPL types using meta-analysis.

This work retrieved published literature about association between COVID-19 and aPL from Embase, Web of Science, PubMed, and The Cochrane Library databases. The observation group was COVID-19 patients, and the control group was healthy individuals. Outcome measures contained any of following aPLs: classic aPL: anti-cardiolipin antibodies (aCL) and anti-β2-glycoprotein-1 antibodies (Anti-β2GP1); other non-criteria aPL: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and anti-annexin-V antibodies (AnV). Meta-analysis was done on Review Manager 5.4.

10 studies involving 2288 patients were deemed eligible for inclusion. The results of the meta-analysis showed that the prevalence of Classic aPL and Any aPL in the COVID-19 group was significantly higher than in the healthy group (Classic aPL, RR = 2.55, 95 % CI = 1.83-3.55, P < 0.00001; Any aPL, RR = 2.34, 95 % CI = 1.46-3.77, P = 0.0005). Anti-β2GP1 IgA antibodies were the most common aPL in COVID-19 patients, with a significantly higher prevalence than in the healthy group (RR = 4.26, 95 % CI = 2.84-6.40, P < 0.00001). The prevalence of the four types of IgM aPL was significantly higher in the COVID-19 group compared to the healthy group, while there was no significant difference in aPL IgG between the two groups.

The prevalence of aPL in COVID-19 patients was significantly higher than in the healthy control group. IgM aPL was more easily detectable in the early stages of COVID-19 infection, while IgG aPL may be of more concern in the later time points of the immune epidemiology following SARS-CoV-2 infection.

Objective To determine whether nutritional status is related to the incidence of thrombosis and mortality in patients with coronavirus disease 2019 (COVID-19). Methods A total of 496 consecutive patients who were admitted and diagnosed with COVID-19 between April 2020 and March 2023 were retrospectively analyzed. The geriatric nutritional risk index (GNRI) on admission was calculated as follows: 14.89×serum albumin (g/dL) +41.7×body mass index/22. Patients were divided into two groups according to the median GNRI values. The endpoint of this study was a composite of in-hospital thrombotic events and mortality. Results The median GNRI value was 99.3. Patients in the low GNRI (≤99.3) group were older (75±21 vs. 51±20 years, p<0.001) and more likely to be female (55.6% vs. 41.1%, p<0.05). In addition, patients with a low GNRI often exhibited hypertension (43.5% vs. 28.2%, p<0.001) and had a history of cardiovascular disease (34.3% vs. 14.5%, p<0.001). Under these conditions, the median D-dimer levels on admission were significantly higher in patients with a low GNRI (0.90 μg/mL; interquartile range (IQR), 0.49-1.64 μg/mL) than those with high GNRI (0.36 μg/mL; IQR, 0.26-0.51 μg/mL, p<0.001). During hospitalization, the composite endpoint was observed in 32 patients. In the logistic regression analysis, a low GNRI was significantly associated with the composite endpoint adjusted using inverse probability of treatment weighting (odds ratio, 3.24; 95% confidence interval: 1.51-6.93, p<0.05). Conclusion Assessment of the GNRI provides useful information for predicting in-hospital thrombosis and mortality in COVID-19 patients.

Thromboembolic (TE) complications in COVID-19 patients are rising globally, contributing significantly to mortality, particularly in severe cases. However, their prevalence, characteristics, and impact on mortality in Malaysia remain unclear.

This study aimed to determine the prevalence of thromboembolic (TE) events and associated mortality among COVID-19 patients admitted within a single centre intensive care unit (ICU). The proportions of patients with TE events who died, and factors associated with TE events were explored.

In this retrospective cohort study, patients with PCR confirmed SARS-CoV-2 virus and who received thromboprophylaxis within February 2020-2021 were included. TE event is a combination of venous [(deep vein thrombosis (DVT), pulmonary embolism (PE)] and arterial (myocardial infarction (MI), stroke) thromboembolism.

Mean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU stay, 64.2%, 53.2% and 20.9% had underlying hypertension, diabetes and obesity respectively. In total, 240 (44.9%) developed TE event. Significantly higher proportions of COVID-19 patients who developed complications of DVT (2.5% vs. 0.2%; p = 0.013), PE (47.5% vs 34.0%; p = 0.006), stroke (12.3% vs. 1.5; p<0.001) and MI (16.4% vs. 4.6%; p<0.001) died. Predictors of TE events were age [HR 1.01 (95% CI 1.00-1.02)], obesity [HR 1.98 (95% CI 1.51-2.6)], D-dimer [HR 1.01 (95% CI 1.00-1.01)], and duration of ICU stay [HR 0.98 (95% CI 0.97-0.99)].

In severely ill COVID-19 patients, TE complications were common, and patients with DVT, PE, stroke, or MI faced increased mortality, even with thromboprophylaxis. Age, obesity, elevated D-Dimer levels, and longer ICU stays were significant predictors of TE events. Considering these findings, a more aggressive approach, combining thromboprophylaxis with enhanced anti-inflammatory treatments, may be necessary for high-risk COVID-19 ICU patients to reduce TE events and mortality.

Same-day emergency care (SDEC) is an expanding area of hospital acute medical care. It aims to minimize delays and manage medical emergency patients within the same day, enabling hospitalization to be avoided; the expectation is that the patients would have required inpatient hospitalization in the absence of the SDEC service. Venous thromboembolism (VTE) prevention is a key medical inpatient safety measure. Whether VTE prevention should be considered for SDEC patients is unknown.

To examine the incidence and predictors of VTE diagnosed within 90 days of SDEC assessment.

Data were obtained from electronic health records of people who received SDEC at our hospital during a 5-year period (April 2016 to March 2021).

There were 40 045 attendance episodes by 33 715 individuals. Median age was 60 years (IQR, 41.0-76.0 years), and 55.2% were women. Three hundred forty-nine patients (0.9%) developed a VTE within 90 days of SDEC. Increased risk of VTE was associated with age more than 60 years, prior malignancy (adjusted odds ratio [OR], 4.12; 95% CI, 3.19-5.32; P < .0001), history of diseases of the circulatory system (adjusted OR, 2.92; 95% CI, 2.27-3.76; P < .0001), and having 1 or more additional SDEC attendances within 30 days (adjusted OR, 4.61; 95% CI, 3.65-5.82; P < .0001). In the 90 days prior to VTE diagnosis, 36.6% of patients had a separate inpatient admission in addition to SDEC. There was no association with completion of an electronic VTE risk assessment (adjusted OR, 0.96; 95% CI, 0.76-1.20).

The incidence of VTE following SDEC is similar to that reported for symptomatic VTE in traditional medical inpatients without thromboprophylaxis.

Acute portomesenteric venous thrombosis (PVT) is a rare but potentially life-threatening condition in individuals without cirrhosis. Initial management typically involves anticoagulation therapy, but the optimal approach to interventional treatment remains a topic of ongoing research. This article explores both traditional and emerging endovascular techniques, providing an overview of the existing evidence supporting their use. Additionally, it delves into the significance of acute PVT in the context of contemporary pathologies, notably coronavirus disease 2019 infection, vaccine-induced immune thrombotic thrombocytopenia, and liver transplantation.

Covid 19 patients often present with elevated D-dimer levels. The purpose of this study is to evaluate the role of D-Dimer levels in Covid 19 patients to predict mortality and venous thromboembolism (VTE) events. This is a retrospective chart review study from 1 April 2020 to 30 June 2020, during the peak Covid pandemic. A total of 350 patients were enrolled in this study; 69 (19.7%) patients died; 12 (3.4%) had a deep venous thrombosis; and 8 (2.3%) had a pulmonary embolism outcome. Peak D-dimer levels were collected with median levels of 765 ng/ml (266, 3135). Patients with VTE outcomes had significantly higher levels of peak D-dimers than patients in the non-VTE group (4876 vs 680, p < 0.0001). Patients who died had higher peak D-dimer levels than those who survived (4690 vs 501, p < 0.0001). The optimal cutoff point in peak D-dimer in predicting VTE events was 1437, yielding a sensitivity of 84.2% and a specificity of 65.0%. The optimal cutoff point in peak D-dimer in predicting mortality was 2004, yielding a sensitivity of 71.0% and a specificity of 77.9%. This study suggests that D-dimer levels can be elevated in Covid 19 hospitalized patients and can serve as indicators for mortality and VTE events.

We aimed to investigate the incidence of new acute myocardial infarction (AMI), in patients with Coronavirus disease (COVID-19) who had old MI. We hypothesized that COVID-19 increases the rate of repeated AMI in this population regardless of age and gender.

A retrospective analysis was conducted for adult patients admitted with COVID-19 and developed thromboembolic event (TEE) in 2020. Patients were categorized based on the history of old MI, new MI, age, and gender.

Among 16,903 patients with COVID-19 who were admitted, 210 (1.2%) developed TEE (89% were males, 55% were <55 years old, and 80.5% had an old MI). COVID-19 was severe in 32% of cases. AMI occurred in 160 patients (42.5% STEMI and 57.5% NSTEMI). In patients with prior MI, 92.5% developed another AMI. NSTEMI was higher in patients with severe COVID-19 than STEMI (33% vs 21%). Patients with severe COVID-19 had higher mortality (39.4% vs 5.6%), fewer rates of prior MI (74% vs 83%), hypertension (40% vs 60%), and STEMI (31.8% vs 46.5%) than mild COVID-19 patients. On multivariable analysis, COVID-19 severity was an independent predictor of mortality (OR10; 95%CI 1.62-67.19) after adjustment for age, gender, diabetes mellitus, C-reactive protein, serum Ferritin, Procalcitonin, and Fibrinogen values, and prior or new MI.

Patients with old MI could develop a new AMI in 80% of COVID-19. However, the mortality was higher in patients without a history of MI due to the severity of COVID-19. Attention should be given to patients who possess thrombotic risk factors in pandemics.

Previous research has shown that vaccination reduces risk of post-coronavirus disease 2019 (COVID-19) venous thrombosis or embolism (VTE), but the effect of vaccine boosting on post-COVID-19 VTE risk reduction is unclear. We sought to estimate the effect of COVID-19 vaccination on the risk of post-COVID-19 VTE and to examine if the magnitude of this association differed among variant eras.

We performed a case-control study of Military Health System (MHS) beneficiaries who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020-2022. Cases were defined as those with medically attended VTE within 90 days after their first positive SARS-CoV-2 test; controls were defined as SARS-CoV-2 infections without incident VTE by 90 days. Multivariate logistic regression estimated the odds of post-SARS-CoV-2 VTE based on pre-COVID-19 vaccine status, adjusting for other VTE risk factors.

A total of 4646 MHS beneficiaries were included in this analysis; 1370 received a primary vaccine series and a further 790 received at least 1 booster at time of infection; 71 had VTE within 90 days of SARS-CoV-2 infection. Those who were vaccinated had lower odds of VTE (adjusted odds ratio [95% confidence interval]) compared to the unvaccinated following infection (primary series: 0.28 [.13-.62]; booster dose: 0.06 [.01-.46]). Post-COVID-19 VTE risk was lowest during the Omicron era, but VTEs were too rare to examine for an interaction of variant era and vaccine effect.

Among MHS beneficiaries, COVID-19 vaccination was associated with a reduced risk of post-COVID-19 VTE diagnosis; estimated risk reduction was larger among those who received a booster.

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed "immunothrombosis". In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms.

Inflammation contributes to the development of thrombosis, but the mechanistic basis for this association remains poorly understood. Innate immune responses and coagulation pathways are activated in parallel following infection or injury, and represent an important host defense mechanism to limit pathogen spread in the bloodstream. However, dysregulated proinflammatory activity is implicated in the progression of venous thromboembolism and arterial thrombosis. In this review, we focus on the role of myeloid cells in propagating thromboinflammation in acute inflammatory conditions, such as sepsis and coronavirus disease 2019 (COVID-19), and chronic inflammatory conditions, such as obesity, atherosclerosis, and inflammatory bowel disease. Myeloid cells are considered key drivers of thromboinflammation via upregulated tissue factor activity, formation of neutrophil extracellular traps (NETs), contact pathway activation, and aberrant coagulation factor-mediated protease-activated receptor (PAR) signaling. We discuss how strategies to target the intersection between myeloid cell-mediated inflammation and activation of blood coagulation represent an exciting new approach to combat immunothrombosis. Specifically, repurposed anti-inflammatory drugs, immunometabolic regulators, and NETosis inhibitors present opportunities that have the potential to dampen immunothrombotic activity without interfering with hemostasis. Such therapies could have far-reaching benefits for patient care across many thromboinflammatory conditions.

Patients with COVID-19 are at an increased risk for venous thromboembolism (VTE). With the advent of vaccinations and novel treatments from 2020 through 2022, the landscape of COVID-19 has evolved. Notably, the effects of such interventions on the outcomes of COVID-19-associated VTE have not been thoroughly examined. Data from the RIETE registry were analyzed to evaluate 90-day VTE-related outcomes (all-cause mortality, major bleeding, and VTE recurrences) in patients with COVID-19-associated VTE. We compared the periods before and after the widespread introduction of COVID-19 vaccines: March to December 2020 (pre-vaccine period) and March 2021 to December 2022 (post-vaccine period). Statistical analysis included mixed-effects parametric survival-time models. Among 1,620 patients with COVID-19-associated VTE, most (74.1%) were identified during 2020 period. The analysis revealed a more than two-fold increase in the risk of death within 90 days (adjusted hazard ratio [HR]: 2.27; 95% confidence interval, CI: 1.18-4.38) and major bleeding (adjusted HR: 2.91; 95%CI: 1.08-7.84) for patients from the 2020 period compared to those from the 2021-2022 period. Inpatient subgroup analysis confirmed the observed mortality differences. The frequency of recurrent VTE was low (1.1 vs. 0.7%, respectively), and did not show significant variation between the two periods. Our research provides a comparative perspective on the clinical outcomes of COVID-19-associated VTE before and after the introduction of vaccines. Our findings reveal a significant decrease in the incidence of 90-day mortality and major bleeding in patients with COVID-19-associated VTE in the 2021-2022 period.

The high prevalence of deep vein thrombosis (DVT) in patients admitted to intensive care unit (ICU) for COVID-19-related acute respiratory distress syndrome (ARDS) would justify systematic screening of these patients or higher therapeutic dose of heparin for thromboprophylaxis.

We performed a systematic echo-Doppler of the lower limb proximal veins during the first 48 h (visit 1) and from 7 to 9 days after visit 1 (visit 2) in consecutive patients admitted to the ICU of a university-affiliated tertiary hospital for severe proven COVID-19 during the second wave. All patients received intermediate-dose heparin (IDH). The primary objective was to determine DVT incidence on venous Doppler ultrasound. Secondary objectives were to determine whether the presence of DVT modifies the anticoagulation regimen, the incidence of major bleeding according to International Society on Thrombosis and Haemostasis (ISTH) criteria, and the mortality rate of patients with and without DVT.

We included 48 patients (30 [62.5%] men) with a median age of 63 years [IQR, 54-70]. The prevalence of proximal deep vein thrombosis was 4.2% (2/48). In these two patients, after DVT diagnosis, anticoagulation was changed from intermediate to curative dose. Two patients (4.2%) had a major bleeding complication according to ISTH criteria. Among the 48 patients, 9 (18.8%) died before hospital discharge. No DVT or pulmonary embolism was diagnosed in these deceased patients during their hospital stay.

In critically ill patients with COVID-19, management with IDH results in a low incidence of DVT. Although our study is not designed to demonstrate any difference in outcome, our results do not suggest any signal of harm when using intermediate-dose heparin (IDH) COVID-19 with a frequency of major bleeding complications less than 5%.

To identify the features of plasma, platelet hemostasis, and proteomic composition of the blood plasma in patients with acute myocardial infarction (AMI) and healthy volunteers after COVID-19.

The study included patients with AMI who have recently had COVID-19 (AMI-post-COVID, n=56) and patients with AMI who have not recently had COVID-19 (AMI-control, n=141). Healthy volunteers constituted the control groups and were also divided into control-post-COVID (n=32) and control-control (n=71) groups. Previous SARS-CoV-2 infection was determined by anti-N IgG in the blood serum, the level of which persists for 6-10 months after the disease. Hemostasis was evaluated by thromboelastometry (on whole blood), thrombodynamics (on platelet-poor plasma), fibrinolysis, impedance aggregometry, and proteomic analysis.

The AMI-post-COVID and AMI-control groups had higher values of thrombus growth rate, size and density based on the data of thromboelastometry and thrombodynamics, as well as increased concentrations of the complement system components, proteins regulating the state of the endothelium, and a number of acute-phase and procoagulant proteins compared to the control groups. Furthermore, in the AMI-post-COVID group, compared to the AMI-control group, the thrombus density was lower, and its lysis rates were higher when measured by the thrombodynamics method on platelet-poor plasma, while the platelet aggregation induced by ADP and thrombin was higher. Also, in the control-post-COVID group, compared to the control-control group, the thrombus formation rate was lower, whereas, in contrast, the thrombus size as measured by the thrombodynamics method and the platelet aggregation induced by arachidonic acid and thrombin were higher. In addition, in the AMI-post-COVID group, compared to the AMI-control group, the concentrations of proteins involved in inflammation and hemostasis were lower.

Patients with AMI who have recently had COVID-19 are characterized by a less pronounced activation of the immune response compared to patients with AMI who have not had COVID-19. This may be due to long-term chronic inflammation and depletion of components of the immune activation system after SARS-CoV-2 infection. Long-term activation of the hemostasis system in both patients with AMI and healthy volunteers after COVID-19 is primarily due to the platelet component of hemostasis.

Amubarvimab-romlusevimab is a commonly recommended antiviral treatment in China for adult patients with mild or moderate SARS-CoV-2 infections, especially for patients with a high risk factor for progression to severe COVID-19. However, its exact efficacy in patients with severe Covid-19 is not yet known.This is a single-center retrospective cohort study, in which we collected the general data, laboratory tests, radiological characteristics, viral conversion status, and prognosis of the disease from patients with COVID-19 hospitalized, from December 2022 to March 2023 in the Department of Critical Care Medicine. The amubarvimab-romlusevimab therapy can reduce the 28-day mortality (29.79 % vs 51.35 %, p = 0.02), and ICU mortality (29.79 % vs 55.41 %, p = 0.006) of severe COVID-19.A 1:1 PSM (Propensity Score Matching) was performed to reduce bias, in order to ensure the two groups were balanced and comparable. In the matched population (n = 47), there were no statistically significant differences between the mAbs (monoclonal antibody)group and the Non-antiviral group in 28-day, and thromboembolic events in COVID-19 patients. The 40-day survival analysis shows that mAbs therapy can improve patient prognosis (HR = 0.45, 95%CI = 0.26-0.76, p = 0.008). However, no significant intergroup difference in the 40-day cumulative viral conversion rate. In a univariate Cox regression analysis, The Amubarvimab - romlusevimab therapy(HR:0.464; CI:[0.252-0.853]; p:0.013) is a protective factor and CRP, PCT, PLT, Lactate, PT, PT-INR, and pt% level at admission were risk factors for clinical prognosis. After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211-0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19.

COVID-19 induces the development of autoimmune diseases, including SLE, which are characterised by inflammation, autoantibodies and thrombosis. However, the effects of COVID-19 on SLE remain unclear.

We investigated the effects of COVID-19 on SLE development and progression in three animal models. Plasmids encoding SARS-CoV-2 spike protein and ACE2 receptor were injected into R848-induced BALB/C lupus mice, R848-induced IL-1 receptor antagonist knockout (KO) lupus mice and MRL/lpr mice. Serum levels of albumin and autoantibodies, lymphocyte phenotypes and tissue histology were evaluated.

In R848-induced BALB/C lupus mice, the SARS-CoV-2 spike protein increased autoantibody and albumin levels compared with vehicle and mock treatments. These mice also exhibited splenomegaly, which was further exacerbated by the spike protein. Flow cytometric analysis revealed elevated T helper 1 cell counts, and histological analysis indicated increased levels of the fibrosis marker protein α-smooth muscle actin. In KO mice, the spike protein induced splenomegaly, severe kidney damage and pronounced lung fibrosis. In the MRL/lpr group, spike protein increased the serum levels of autoantibodies, albumin and the thrombosis marker chemokine (C-X-C motif) ligand 4.

COVID-19 accelerated the development and progression of lupus by inducing autoantibody production, fibrosis and thrombosis.

Coagulopathy and thromboembolic events are associated with poor outcomes in coronavirus disease 2019 (COVID-19) patients. There is conflicting evidence on the effects of chronic anticoagulation on mortality and severity of COVID-19 disease.

To summarize the body of evidence on the effects of pre-hospital anticoagulation on outcomes in COVID-19 patients.

A Literature search was performed on LitCovid PubMed, WHO, and Scopus databases from inception (December 2019) till June 2023 for original studies reporting an association between prior use of anticoagulants and patient outcomes in adults with COVID-19. The primary outcome was the risk of thromboembolic events in COVID-19 patients taking anticoagulants. Secondary outcomes included COVID-19 disease severity, in terms of intensive care unit admission or invasive mechanical ventilation/intubation requirement in patients hospitalized with COVID-19 infection, and mortality. The random effects models were used to calculate crude and adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs).

Forty-six observational studies met our inclusion criteria. The unadjusted analysis found no association between prior anticoagulation and thromboembolic event risk [n = 43851, 9 studies, odds ratio (OR)= 0.67 (0.22, 2.07); P = 0.49; I 2 = 95%]. The association between prior anticoagulation and disease severity was non-significant [n = 186782; 22 studies, OR = 1.08 (0.78, 1.49); P = 0.64; I 2 = 89%]. However, pre-hospital anticoagulation significantly increased all-cause mortality risk [n = 207292; 35 studies, OR = 1.72 (1.37, 2.17); P < 0.00001; I 2 = 93%]. Pooling adjusted estimates revealed a statistically non-significant association between pre-hospital anticoagulation and thromboembolic event risk [aOR = 0.87 (0.42, 1.80); P = 0.71], mortality [aOR = 0.94 (0.84, 1.05); P = 0.31], and disease severity [aOR = 0.96 (0.72, 1.26); P = 0.76].

Prehospital anticoagulation was not significantly associated with reduced risk of thromboembolic events, improved survival, and lower disease severity in COVID-19 patients.

COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin.

This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed.

10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]).

Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

A growing body of research has shown that patients with coronavirus disease 2019 (COVID-19) have significantly higher rates of venous thromboembolism (VTE) than healthy. However, the mechanism remains incompletely elucidated. This study aimed to further investigate the molecular mechanisms underlying the development of this complication.

The gene expression profiles of COVID-19 and VTE were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the common differentially expressed genes (DEGs) for COVID-19 and VTE, functional annotation, a protein-protein interactions (PPI) network, module construction, and hub gene identification were performed. Finally, we constructed a transcription factor (TF)-gene regulatory network and a TF-miRNA regulatory network for hub genes.

A total of 42 common DEGs were selected for subsequent analyses. Functional analyses showed that biological function and signaling pathways collectively participated in the development and progression of VTE and COVID-19. Finally, 8 significant hub genes were identified using the cytoHubba plugin, including RSL24D1, RPS17, RPS27, HINT1, COX7C, RPL35, RPL34, and NDUFA4, which had preferable values as diagnostic markers for COVID-19 and VTE.

Our study revealed the common pathogenesis of COVID-19 and VTE. These common pathways and pivotal genes may provide new ideas for further mechanistic studies.

SARS-CoV-2 infection starts from the association of its spike 1 (S1) subunit with sensitive cells. Vesicular endothelial cells and platelets are among the cell types that bind SARS-CoV-2, but the effectors that mediate viral attachment on the cell membrane have not been fully elucidated. Herein, we show that P-selectin (SELP), a biomarker for endothelial dysfunction and platelet activation, can facilitate the attachment of SARS-CoV-2 S1. Since we observe colocalization of SELP with S1 in the lung tissues of COVID-19 patients, we perform molecular biology experiments on human umbilical vein endothelial cells (HUVECs) to confirm the intermolecular interaction between SELP and S1. SELP overexpression increases S1 recruitment to HUVECs and enhances SARS-CoV-2 spike pseudovirion infection. The opposite results are determined after SELP downregulation. As S1 causes endothelial inflammatory responses in a dose-dependent manner, by activating the interleukin (IL)-17 signaling pathway, SELP-induced S1 recruitment may contribute to the development of a "cytokine storm" after viral infection. Furthermore, SELP also promotes the attachment of S1 to the platelet membrane. Employment of PSI-697, a small inhibitor of SELP, markedly decreases S1 adhesion to both HUVECs and platelets. In addition to the role of membrane SELP in facilitating S1 attachment, we also discover that soluble SELP is a prognostic factor for severe COVID-19 through a meta-analysis. In this study, we identify SELP as an adhesive site for the SARS-CoV-2 S1, thus providing a potential drug target for COVID-19 treatment.

 Neutrophil NETosis and neutrophil extracellular traps (NETs) play a critical role in pathogenesis of coronavirus disease 2019 (COVID-19)-associated thrombosis. However, the extents and reserve of NETosis, and potential of thrombus formation under shear in whole blood of patients with COVID-19 are not fully elucidated. Neither has the role of recombinant ADAMTS13 or caplacizumab on the accumulation of NETs and thrombus in COVID-19 patients' whole blood under shear been investigated.

 Flow cytometry and microfluidic assay, as well as immunoassays, were employed for the study.

 We demonstrated that the percentage of H3Cit + MPO+ neutrophils, indicative of NETosis, was dramatically increased in patients with severe but not critical COVID-19 compared with that in asymptomatic or mild disease controls. Upon stimulation with poly [I:C], a double strain DNA mimicking viral infection, or bacterial shigatoxin-2, the percentage of H3Cit + MPO+ neutrophils was not significantly increased in the whole blood of severe and critical COVID-19 patients compared with that of asymptomatic controls, suggesting the reduction in NETosis reserve in these patients. Microfluidic assay demonstrated that the accumulation of NETs and thrombus was significantly enhanced in the whole blood of severe/critical COVID-19 patients compared with that of asymptomatic controls. Like DNase I, recombinant ADAMTS13 or caplacizumab dramatically reduced the NETs accumulation and thrombus formation under arterial shear.

 Significantly increased neutrophil NETosis, reduced NETosis reserve, and enhanced thrombus formation under arterial shear may play a crucial role in the pathogenesis of COVID-19-associated coagulopathy. Recombinant ADAMTS13 or caplacizumab may be explored for the treatment of COVID-19-associated thrombosis.

While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED.

This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve.

A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100% vs. 82%, p = 0.020) and admitted to the ICU (64% vs. 24%, p = 0.002). Those with PE had a significantly higher median DD value (21,177 ng/mL) compared to PE-negative group (952 ng/mL, p < 0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815 ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089 ng/mL could be used with sensitivity 100% and specificity 58%.

DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500 ng/mL, our study demonstrated a threshold of 1089 ng/mL safely predicted PE in patients with COVID-19 .

Data on characteristics and outcomes of coronavirus (COVID)-19 patients complicated with arterial thrombosis (AT) are scarce. Therefore, we carried out a systematic review (PRISMA, PROSPERO statements; PubMed, Scopus, and Web of Science) to identify risk factors, clinical presentation, treatment, and outcomes. We included publications from December 2019 to October 2020. Groups: (a) ischemic stroke, (b) thrombotic storm, (c) peripheral vascular thrombosis, (d) myocardial infarction, and (e) left cardiac thrombus or in-transit thrombus (venous system thrombus floating or attaching to the right heart). We considered 131 studies. The most frequent cardiovascular risk factors were: hypertension, diabetes, and dyslipidemia. A high proportion presented with asymptomatic, mild, or moderate COVID-19 (n = 91, 41.4%). We identified a high percentage of isolated ischemic stroke and thrombotic storm. Groups with higher mortality rate: intracardiac thrombus (1/2, 50.0%), thrombotic storm (18/49, 36.7%), and ischemic stroke (48/131, 36.6%). A small number received thromboprophylaxis. Most patients received antithrombotic treatment. The most frequent bleeding complication was intracranial hemorrhage, primarily with isolated stroke. Overall mortality was 33.6% (74/220). Despite a wide range of COVID-19 severity, a high proportion had AT as a complication of non-severe disease. AT can affect different vascular territories; mortality is associated with stroke, intensive care unit stay, and severe COVID-19.

Patients who undergo metabolic and bariatric surgery (MBS) are at risk for thromboembolism. Patients are susceptible to coronavirus throughout the perioperative period, which also has a well-known association with thrombotic complications.

To identify and define the association between venous thromboembolism (VTE) and postoperative coronavirus diagnosis in bariatric surgery patients.

United States.

We conducted a retrospective cohort study using the MBS Accreditation and Quality Improvement Program (MBSAQIP) 2021 database to analyze the incidence of VTE within 30 days of surgery. VTE was a composite variable defined as either postoperative pulmonary embolism or postoperative venous thrombus requiring treatment. Cohorts were stratified by whether the patient was diagnosed with postoperative coronavirus. We created a multivariable logistic regression model to determine the adjusted odds of postoperative VTE based on various factors. Additionally, we conducted subset analyses of sleeve gastrectomy and Roux-en-Y bypass cases, the 2 most frequent bariatric operations in the United States.

Patients diagnosed with postoperative coronavirus were significantly more likely to develop postoperative VTE (1.1% versus .3%, P < .001). In our logistic regression model, the adjusted odds of postoperative VTE for patients with postoperative coronavirus was 3.55 (95% CI: 2.15-5.87, P < .001). For patients who underwent Roux-en-Y bypass, the adjusted odds was even greater at 5.69 (95% CI: 2.76-11.70, P < .001).

Early postoperative coronavirus infection after MBS is associated with higher odds of postoperative VTE. This persisted on subset analyses of the 2 most common procedures and appeared particularly important for Roux-en-Y bypass. COVID infection after MBS may warrant prolonged VTE prophylaxis.

There is no information on renal vein thrombosis induced by COVID-19 infection in a neonate. Few cases of renal vein thrombosis caused by COVID-19 infection have been reported in predominantly adult patients. On day 25 after birth, a newborn whose mother was infected with COVID-19 had renal vein thrombosis. We believed that our patient's renal vein thrombosis was caused by postnatal transmission of the COVID-19 infection that the mother had acquired during birth. The clinical and radiologic findings of these unusual renal complications in a neonate, as well as treatment options, are presented.

In 2019, the emergence of SARS-CoV-2 marked the beginning of the COVID-19 global pandemic, which reached its peak in 2020. Initially designated as a novel coronavirus, SARS-CoV-2 emerged as a respiratory illness and later began causing multi-organ complications in recovered patients.

This article presents a hospital-based retrospective cohort study conducted via telephone interviews with patients in a tertiary hospital. After obtaining verbal consent from the subjects, the study utilized a semi-structured questionnaire to gather data.

In the 54-person cohort group, 64.8% were males and 35.1% were females. The mean duration of the male patients' hospital stays was greater than that of the female patients. However, the mean lag time between the onset of comorbidities and recovery from COVID-19 was shorter in females than in males. Upon further analysis, it was revealed that female patients are more susceptible to the development of multiple comorbidities at once, occurring in 37.5% of the female patients in this study. Diabetes mellitus alone had the highest incidence rate (12.9%), followed by ST-elevation myocardial Infarctions (7.4%) and thrombocytopenia (5.5%). Of the cohort group, 51.8% developed comorbidities after exposure to COVID-19, while about 14.8% of the control group developed comorbidities from March 2020 onwards, i.e. from the commencement of the COVID-19 global pandemic. The relative risk assessed for this study is 3.5. The study's attributable risk is 71.42%.

The incidence of comorbidities in the cohort group was greater than that in the control group, demonstrating COVID-19 as a risk factor for post-exposure comorbidities. It is clear that there is a direct association between COVID-19 and the development of comorbidities, which is inferred with a relative risk of 3.5.

Objective: Observational studies show the correlation between COVID-19 and venous thromboembolism (VTE) risk. However, the causal effects remain uncertain. We aimed to explore the potential causal association between COVID-19 and VTE using Mendelian randomization (MR) design. Methods: Two-sample MR was used to evaluate the potential causality between COVID-19 and VTE by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The weighted median, MR-Egger, simple mode, and weighted mode were employed as supplementary methods for MR estimations, with the inverse-variance weighted (IVW) method serving as the principal analysis. In addition, we took sensitivity analyses, including Cochran's test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analysis to ensure that we obtained stable and reliable results. Results: Our study selected 26 COVID-19 severity, 31 COVID-19 hospitalization, and 13 COVID-19 susceptibility SNPs as instrumental variables. The IVW analysis results revealed that there was no causal relationship between COVID-19 severity, hospitalization, or susceptibility and VTE, with odds ratios of 0.974 (95%CI: 0.936-1.013, p = 0.19), 0.976 (95%CI: 0.918-1.039, p = 0.447), and 0.908 (95%CI: 0.775-1.065, p = 0.235), respectively. The IVW approach yielded consistent results with MR-Egger, Weighted Median simple mode, and weighted mode. MR-PRESSO and sensitivity analysis further confirmed the stability and consistency of the MR results. Conclusions: This study did not find evidence to support a causal relationship between COVID-19 and VTE at the genetic level. Further investigation is warranted to determine if the significant association reported in previous observational studies between the two is due to confounding factors.