Thromboembolism In COVID-19 Research Articles

Abstract 13625: Association of Antiphospholipid Antibodies With Venous Thromboembolism in COVID-19

Introduction: Coagulation abnormalities leading to arterial and venous thrombotic events have been described in patients with COVID-19 and studies have reported an overall pooled incidence of venous thromboembolism (VTE) of 17%, however little is known regarding VTE association with antiphospholipid antibodies in patients with COVID-19. Hypothesis: Antiphospholipid antibodies are associated with VTE events in COVID-19. Methods: This is a retrospective cohort study of COVID-19 patients hospitalized at the University of Virginia Medical Center (UVA). Serum samples were collected and stored in the UVA COVID-19 biorepository. Anti-cardiolipin (aCL) and anti-b2glycoprotein1(ab2GLP1), IgM/IgG titres, were measured from stored samples, using the enzyme-linked immunosorbent assay (ELISA). Specimens were analysed at two distinct time-points/days during the patient’s hospitalization for COVID-19. VTE incidence was collected retrospectively by chart review. The study was approved by the Institutional Review Board at UVA. Two-tailed Mann-Whitney two-sample rank-sum tests were conducted to examine whether there were significant differences in APS antibody levels, and mean change in APS levels between the two time points analysed, and VTE events. Additionally, logistic regression models were constructed to examine whether APS antibody levels and mean change in APS levels had a significant effect on the odds of observing a case of VTE. Results: There were 53 patients included in the study. The mean age of participants was 57.2 years (SD 13.9). VTE did not corelate with the levels of APS at studied time points, or the mean change in APS levels during the disease course. aCL IgM (p = 0.24), aCL IgG (p = 0.92), ab2GLP1 IgM (p = 0.79), and ab2GLP1 IgG (p = 0.79). Changes in the APS antibody levels during the course of the disease were not predictive of the odds of having VTE. Similarly, these changes did not predict the need for ICU care. Conclusions: This study shows that neither the presence of antiphospholipid antibodies nor the change in APS levels during the course of COVID-19 correlated with VTE events.

Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis

Background: A high incidence of venous thromboembolism (VTE) is reported in hospitalized COVID-19 patients, in particular in patients admitted to the intensive care unit (ICU). In patients with respiratory tract infections, including influenza A (H1N1), many studies have demonstrated an increased incidence of thromboses, but evidence is lacking regarding the risk difference (RD) of the occurrence of VTE between COVID-19 and non-COVID-19 patients. Methods: In this systematic review with meta-analysis, we evaluated the RD of the occurrence of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) between COVID-19 and other pulmonary infection cohorts, in particular H1N1, and in an ICU setting. We searched for all studies comparing COVID-19 vs. non-COVID-19 regarding VTE, PE, and DVT. Results: The systematic review included 12 studies and 1,013,495 patients. The RD for VTE in COVID-19 compared to non-COVID-19 patients was 0.06 (95% CI 0.11–0.25, p = 0.011, I2 = 97%), and 0.16 in ICU (95% CI 0.045–0.27, p = 0.006, I2 = 80%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.03 (95% CI, 0.006–0.045, p = 0.01, I2 = 89%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.021 in retrospective studies (95% CI 0.00–0.04, p = 0.048, I2 = 92%) and 0.11 in ICU studies (95% CI 0.06–0.16, p < 0.001, I2 = 0%). Conclusions: The growing awareness and understanding of a massive inflammatory response combined with a hypercoagulable state that predisposes patients to thrombosis in COVID-19, in particular in the ICU, may contribute to a more appropriate strategy of prevention and earlier detection of the thrombotic events.

County-Level Social Vulnerability Is Associated with Increased Risk for Venous Thromboembolism in COVID-19

County-Level Social Vulnerability Is Associated with Increased Risk for Venous Thromboembolism in COVID-19

Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with risk for thromboembolic complications and mortality in patients with COVID-19

Abstract Background/Introduction The high prevalence of thromboembolism in patients with COVID-19 causes significant morbidity and mortality. The soluble urokinase-type plasminogen activator receptor (suPAR), a known inflammatory and immune mediator in several renal and cardiovascular conditions, has recently been shown to correlate with acute kidney injury and severe respiratory failure in COVID-19. To date, no study has investigated the association between suPAR and thromboembolism in COVID-19. Purpose To evaluate associations between suPAR, thromboembolic complications, and mortality in COVID-19. Methods We conducted a retrospective cohort study of a random sample of 109 patients among those hospitalised at a tertiary medical centre comprising three hospitals between March and June 2020 for COVID-19 who had blood samples collected and stored on admission. Serum suPAR was measured using a commercially available enzyme immunoassay. Baseline (hospital admission) variables extracted from electronic medical records included age, sex, race/ethnicity, body mass index (BMI), history of cardiovascular disease (including deep venous thrombosis [DVT] and pulmonary embolism [PE]), serum creatinine, serum D-dimer, incident DVT/PE, and death during hospitalization. Patients were subsequently grouped by suPAR quartiles. Associations between suPAR, thromboembolic complications (PE and/or DVT), and overall mortality were evaluated using multivariable logistic regression. Results Among the 109 patients, mean age was 56 (standard deviation [SD], 16) years, 34 (39%) were women, mean BMI was 35 (SD, 8) kg/m2, 78 (71%) had coexisting cardiovascular disease, median creatinine level was 1.2 (interquartile range [IQR]: 0.8–2.3) mg/dl, median D-dimer level was 1.5 (IQR, 0.8–6.4) μg/ml, and median suPAR level was 10.1 (IQR: 4.1–14.4) pg/mL. Seven (6%) patients were found to have PE, 18 (17%) developed PE/DVT, and 22 (20%) died during the admission (Table). Per quartile higher suPAR level, there was higher risk for PE or DVT (OR=2.02, 95% CI 1.07–3.83, p=0.03). Compared to those in the lowest suPAR quartile, patients in the highest quartile had 11.1 times higher risk for PE/DVT (OR=11.1, 95% CI 1.51–81.8, p=0.02, Figure). SuPAR is also associated with overall mortality, with 2.25 times higher risk of death seen per quartile increase in suPAR level (OR= 2.25, 95% CI 1.24–4.06, p=0.007). Conclusion Higher suPAR levels at the time of hospital admission is associated with higher risk for thromboembolic complications i.e., PE and DVT, as well as mortality in patients with COVID-19. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Rush University Medical Center

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TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID-19 is associated with arterial and venous thrombosis with incidence of 2.3-22% in severe cases and 0-6% in mild cases. Very few case reports exist about cardiac thrombus in COVID-19 patients with Myocardial infarction (MI) but our patient purely had increased thromboembolic risk from COVID-19 without MI. CASE PRESENTATION: A 49-year-old male with a history of HTN, IDDM, CKD stage 3, and asthma presented to the hospital with six days of progressive dyspnea with fever, fatigue, and cough. He tested positive for COVID-19 two days prior. He was hypoxic at 83% on room air. Pertinent physical exam revealed coarse breath sounds bilaterally and no murmurs. Lab work showed creatinine 1.93 mg/dl, troponin 0.357 ng/ml, B-natriuretic peptide (BNP) 275 pg/ml. D-dimer 1,369 ng/ml, Ferritin 1,569 ng/ml, and CRP >8 mg/dl. Chest x-ray showed bilateral patchy nodular opacities. CTA chest showed pneumonia and bilateral effusions without pulmonary embolism. The patient was started on oxygen supplementation, dexamethasone, and enoxaparin 30 mg every 12 hours. On day 2, Remdesivir was initiated as kidney function had improved. The enoxaparin dose was increased to 0.5mg/kg (60 mg every 12 hours) due to worsening D-dimer at 2268 ng/ml. On day 3, he had worsening respiratory failure and was transitioned to a high flow respiratory system on 60L. Repeat BNP increased to 475.4 pg/ml and D-dimer to >7650 ng/ml. Troponin plateaued at 0.3 ng/ml. He was switched to a low-intensity heparin protocol of 10 units/kg/hr. A trans-thoracic echocardiogram (TTE) showed an ejection fraction of 57% with a questionable apical clot and without wall motion abnormality. A TTE with contrast showed a spherical echogenic mass 1.87 x 1.64 cm, consistent with left ventricular (LV) thrombus attached to the septum. He was then switched to a high-intensity heparin protocol of 15 units/kg/hr and then transitioned to warfarin with a plan for outpatient cardiac MRI. On day 11, he was discharged home on 2L of oxygen. DISCUSSION: Thromboembolic disease is a well-known complication of COVID-19. The pathophysiology of thromboembolism in COVID-19 is multifactorial including platelet dysfunction, viral-mediated endothelial inflammation, hypercoagulability, and acquired antiphospholipid antibodies.LV thrombus is a known complication of MI and dilated cardiomyopathy but our patient did not have associated MI. His only apparent predisposing factor was hypercoagulability due to COVID-19. TTE with contrast increases the visibility of the thrombus. But, cardiac MRI with contrast remains the gold standard for its diagnosis. Anticoagulation is the mainstay of treatment as it reduces the major adverse cardiac events (MACE) and overall mortality. CONCLUSIONS: Cardiac thrombus is a rare thromboembolic phenomenon that needs to be considered in COVID-19 patients with or without MI. Immediate parenteral anticoagulation is key for reducing complications. REFERENCE #1: Roberts KA, Colley L, Agbaedeng TA, Ellison-Hughes GM, Ross MD. Vascular Manifestations of COVID-19 – Thromboembolism and Microvascular Dysfunction. Front Cardiovasc Med. 2020;7:598400. doi:10.3389/fcvm.2020.598400 REFERENCE #2: Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432 REFERENCE #3: Jadhav KP, Jariwala P. Intra-Cardiac Thrombus in COVID-19 pandemic – Case Series and Review. Eur J Cardiovasc Med. Published online November 23, 2020. doi:10.5083/ejcm20424884.180 DISCLOSURES: No relevant relationships by Tundun babalola, source=Web Response No relevant relationships by Francis Jenkins, source=Web Response No relevant relationships by Nirvi Shah, source=Web Response No relevant relationships by Shraddha Tongia, source=Web Response

AORTOILIAC THROMBOSIS AND LYMPHOCYTOSIS IN A PATIENT WITH COVID-19

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Venous thromboembolism (VTE) and arterial thrombosis (AT) are known complications associated with critically ill COVID-19 patients. We report a case of a patient that developed an acute aortoiliac thrombosis and acute limb ischemia despite high-dose VTE prophylaxis and was subsequently found to have chronic lymphocytic leukemia (CLL). CASE PRESENTATION: A 62-year-old male with coronary artery disease and diabetes was admitted to the intensive care unit for acute hypoxemic respiratory failure from COVID-19 pneumonia. He was treated with Remdesivir, dexamethasone 6mg daily, and enoxaparin 30mg twice daily. On hospital day 5, he developed acute left lower extremity pain with sensory and motor loss and bilateral lower extremities became cold and pale. He had no palpable femoral or popliteal pulses and posterior tibial and dorsalis pedis pulses were not detected by doppler. A CTA demonstrated an acute, nearly occlusive thrombus at the level of the distal infrarenal aorta with extension to bilateral iliac and femoral arteries. The patient was taken emergently to the operating room and underwent percutaneous thrombectomy and left lower extremity fasciotomy. On further review, he was noted to have significant lymphocytosis (83% on admission), an unexpected finding for a patient with COVID-19. As a result, peripheral flow cytometry was performed and demonstrated CD5 positive B-cell leukemia. The patient eventually discharged to acute rehab after a 42-day hospitalization. DISCUSSION: Since the start of the pandemic, the thrombotic complications of COVID-19 have been a major research focus given the high incidence and associated increased risk of mortality. Most of the research has centered around VTE as the incidence among ICU patients with COVID-19 is estimated at 20-30%. The rate of AT is much less with an overall incidence between 2-4% and only 0.4% associated with acute limb ischemia. Our patient was at higher risk for thrombotic complications given his underlying but undiagnosed CLL. His lymphocytosis was striking, particularly because lymphopenia is the usual finding in patients with COVID-19, and further work up revealed the CLL diagnosis. CONCLUSIONS: Thrombotic complications are common and carry a higher risk of mortality in patients with COVID-19. While the rate of AT is much less compared with VTE, critical care practitioners must remain vigilant, particularly when patients are receiving mechanical ventilation and unable to report symptoms, and be mindful of other conditions, potentially undiagnosed, that may further predispose to thrombosis. REFERENCE #1: Jimenez D, Garcia-Sanchez A, Rali P, Muriel A, Bikdeli B, Ruiz-Artacho P, Le Mao R, Rodriguez C, Hunt BJ, Monreal M. Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis. Chest. 2021 Mar;159(3):1182-1196. REFERENCE #2: Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: A systematic review and meta-analysis. EClinicalMedicine. 2020 Dec;29:100639. REFERENCE #3: Tan BK, Mainbourg S, Friggeri A, Bertoletti L, Douplat M, Dargaud Y, Grange C, Lobbes H, Provencher S, Lega JC. Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis. Thorax. 2021 Feb 23:thoraxjnl-2020-215383. DISCLOSURES: No relevant relationships by Amanda Jobe, source=Web Response No relevant relationships by Mohamed Ramez Mourad, source=Web Response

Rigorous Assessment of Guidelines on COVID-19-Related Thrombotic or Thromboembolic Disease: Implications for Clinical Practice of Prevention, Diagnosis, and Treatment.

Purpose Severe COVID-19 patients were prone to develop venous thromboembolism. Unfortunately, to date, there is no evidence of any effective medications for thromboembolism in COVID-19. The management of the disease relies on symptomatic and supportive treatments, giving rise to a variety of guidelines. However, the quality of methodology and clinical recommendations remains unknown. Materials and Methods We searched Medline, Cochrane Library, Web of Science, websites of international organizations and medical societies, and gray literature databases. Four well-trained appraisers independently evaluated the quality of eligible guidelines and extracted recommendations using well-recognized guideline appraisal tools. Furthermore, recommendations were extracted and reclassified according to a composite grading system. Results The search identified 23 guidelines that offered 108 recommendations. Guidelines scored average on AGREE II criteria, with Scope and Purpose and Clarity of Presentation highest. Only five (22%) guidelines provided high-quality recommendations. The existed clinical recommendations were inconsistent in terms of prophylaxis, diagnosis, and treatment of thromboembolic disease to some extent. Conclusion Current guidelines for COVID-19 thromboembolism are generally of low quality, and clinical recommendations on thromboembolism are principally supported by insufficient evidence. There is still an urgent need for more well-designed clinical trials as evidence to prevent adverse events and improve prognosis during COVID-19 treatment.

Title: Covid-19-associated coagulopathy

COVID-19, primarily a respiratory disease, is considered a multi-systemic disease as symptom severity increases. Blood coagulation abnormalities are key features of patients with severe symptoms and indicative of the high risk of both venous and arterial thromboembolism in COVID-19. This prothrombotic condition caused by an interplay of the infectious agent, inflammation, and the blood coagulation system is referred to as COVID-19-associated coagulopathy and characterized by greatly increased D-dimer, high fibrinogen, an extended prothrombin time, and a reduced number of platelets. Due to this high thrombotic potential, prophylactic anticoagulation is recommended in all hospitalized patients. However, the optimal dosage of anticoagulation is still debated. In this article, we provide an overview of the current state of knowledge about COVID-19-associated coagulopathy and discuss clinical therapeutic consequences.

Clinical Guidance of Prevention of Venous Thromboembolism in COVID-19

新型コロナウイルス感染症（COVID-19）では，静脈血栓塞栓症（VTE）を主とした血栓症を高頻度に合併する．そこで，日本のアンケート調査を踏まえ，診療手引きや他のガイドラインを参考に，COVID-19でのVTE予防診療指針を改定し，予防法を提案する．「軽症」：基本的に抗凝固療法は不要とし理学療法（離床，下肢運動，弾性ストッキング）を中心とする．理学療法はVTE予防の基本である．「中等症I」（息切れ，肺炎所見）：抗凝固療法は不要とし，理学療法（間欠的空気圧迫法も含む）を中心とする．「中等症II」（酸素投与が必要）：予防用量である低用量未分画ヘパリンの使用を考慮する．APTT測定による用量調節は必要としない．抗凝固療法中の理学療法併用は必須ではない．「重症」（ICU管理あるいは人工呼吸器）：未分画ヘパリンの投与を行う．投与量は出血リスクを勘案し予防用量とする．Dダイマーの継続的なモニタリングを実施する．本指針は今後も改定する予定である．

Pulmonary Thrombosis and Thromboembolism in COVID-19.

COVID-19, the disease responsible for the devastating pandemic that began at the end of 2019, has been associated with a significantly increased risk of pulmonary thrombosis, even in patients receiving prophylactic anticoagulation. The predilection for thrombosis in COVID-19 may be driven by at least two distinct, but interrelated, processes: a hypercoagulable state responsible for large-vessel thrombosis and thromboembolism and direct vascular and endothelial injury responsible for in situ microvascular thrombosis. The presence of pulmonary thrombosis may explain why hypoxemia is out of proportion to impairment in lung compliance in some patients with COVID-19 pneumonia. Because pulmonary embolism (PE) and COVID-19 pneumonia share many signs and symptoms, diagnosing PE in patients with COVID-19 can be challenging. Given the high mortality and morbidity associated with severe COVID-19 and the concern that aspects of the disease may be driven by thrombosis, many hospital systems have instituted aggressive anticoagulation protocols above standard VTE prophylaxis. In this review, the epidemiologic and pathophysiologic features, diagnosis, and treatment of COVID-19 pulmonary thrombosis and thromboembolism are discussed.

Venous thromboembolism in COVID-19 compared to non-COVID-19 cohorts: A systematic review with meta-analysis

BackgroundMany studies confirmed an association between COVID-19 and venous thromboembolism (VTE). Whether the risk of VTE significantly differed between COVID-19 cohorts and non-COVID-19 cohorts with similar disease severity remains unknown. ObjectivesThe aim of this systematic review with meta-analysis was to compare the rate of VTE between COVID-19 and non-COVID-19 cohorts with similar disease severity. MethodsA systematic literature search (MEDLINE, Embase and Google Scholar) was conducted from January 1, 2020 to March 31, 2021 to identify studies reporting VTE in COVID-19. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals. ResultsSeven studies (41,768 patients) evaluated VTE in COVID-19 cohorts compared to non-COVID-19 cohorts. The overall risk of VTE (RR 1.18; 95%CI 0.79–1.77; p = 0.42; I2 = 54%), pulmonary embolism (RR 1.25; 95%CI 0.77–2.03; p = 0.36; I2 = 52%) and deep venous thrombosis (RR 0.92; 95%CI 0.52–1.65; p = 0.78; I2 = 0%) did not significantly differ between COVID-19 and non-COVID-19 cohorts. However, subgroup analyses suggested an increased risk of VTE amongst CODID-19 versus non COVID-19 cohorts when only patients hospitalized within the intensive care unit (ICU) were considered (RR 3.10; 95%CI 1.54–6.23), which was not observed in cohorts of predominantly non-ICU patients (RR 0.95; 95%CI 0.81–1.11) (Pinteraction = 0.001). ConclusionThere was no signal for a difference in VTE in COVID-19 cohorts compared to non-COVID-19 cohorts, except for the subgroup of patients hospitalized in the ICU. These results should be viewed as exploratory and further studies are needed to confirm these results.

Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis

BackgroundThe prevalence of venous thromboembolic event (VTE) and arterial thromboembolic event (ATE) thromboembolic events in patients with COVID-19 remains largely unknown.MethodsIn this meta-analysis, we systematically searched for observational studies describing...

Exploring the link between vitamin D and clinical outcomes in COVID-19.

The immunomodulating role of vitamin D might play a role in COVID-19 disease. We studied the association between vitamin D and clinical outcomes in COVID-19 patients. This is a retrospective cohort study on COVID-19 patients with documented vitamin D levels within the last year. Vitamin D levels were grouped as ≥ 20 ng/mL or < 20 ng/mL. Main outcomes were mortality, need for mechanical ventilation, new DVT or pulmonary embolism, and ICU admission. A total of 270 patients (mean ± SD) age, 63.81 (14.69) years); 117 (43.3%) males; 216 (80%) Blacks; 139 (51.5%) in 65 and older age group were included. Vitamin D levels were less than 20 ng/mL in 95 (35.2%) patients. During admission, 72 patients (26.7%) died, 59 (21.9%) needed mechanical ventilation, and 87 (32.2%) required ICU. Vitamin D levels showed no significant association with mortality (OR = 0.69; 95% CI, 0.39-1.24; P = 0.21), need for mechanical ventilation (OR = 1.23; 95% CI, 0.68-2.24; P = 0.49), new DVT or PE(OR= 0.92; 95% CI, 0.16-5.11; P = 1.00) or ICU admission (OR = 1.38; 95% CI, 0.81-2.34; P = 0.23). We did not find any significant association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission and the development of thromboembolism in COVID-19 patients.NEW & NOTEWORTHY Low vitamin D has been associated with increased frequency and severity of respiratory tract infections in the past. Current literature linking clinical outcomes in COVID-19 with low vitamin D is debatable. This study evaluated the role of vitamin D in severe disease outcomes among COVID-19 patients and found no association of vitamin D levels with mortality, the need for mechanical ventilation, ICU admission, and thromboembolism in COVID-19.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19

ObjectivesCOVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear.MethodsWe applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19.ResultsIn blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (β [SE]=0.42 [0.09], P = 4.75 × 10−06 and β [SE]=-0.48 [0.11], P = 6.76 × 10−06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation.ConclusionsWe identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

Abstract 14699: Arterial and Venous Thromboembolism in Covid-19: A Study-level Meta-analysis

Introduction: The prevalence of venous (VTE) and arterial (ATE) thromboembolic events in patients with COVID-19 remains largely unknown. Methods: In this systematic review and meta-analysis, we systematically searched Pubmed MEDLINE, Google Scholar, and Web of Science for observational studies describing the prevalence of VTE and ATE amongst patients with COVID-19 published between Jan 1, 2020 and May 20, 2020. The websites of major journals were also searched. Results: We analysed findings from 15 studies totalizing 1,755 patients, mainly in intensive care units (ICU). The weighted frequency of COVID-19-related VTE was 16.6% (95%CI 9.5-25.1%, I 2 =94%, 13 studies: 1,546 patients). The overall prevalence of PE and deep vein thrombosis (DVT) were 9.1% (95%CI 3.7-16.6%, I 2 =95%; 15 studies; 1,755 patients) and, 7.8% (95%CI 3.4-13.8%; I 2 =92%; 13 studies; 1,445 patients), respectively. Few were isolated subsegmental PE or distal DVT. The VTE prevalence was significantly higher in ICU (21.6%; 95%CI 12.6-32.2%; I2=91% versus 4.6%; 95%CI 1.0-10.7%, I 2 =87%, p interaction =0.002 in subgroup analysis). The weighted frequency of myocardial infarction/acute coronary syndrome, stroke, and other ATE (6 studies, 812 patients) was 3.2% (95%CI 2.1-4.5%, I 2 =0%), 0.7% (95%CI 0.0-2.2%, I 2 =64%), 2.0% (95%CI 1.2-3.0%, I 2 =40%), and 0.5% (95%CI 0.0-1.6%, I 2 =60%), respectively. Conclusions: Patients admitted in the ICU for severe COVID-19 had a high risk of VTE. Conversely, further studies are needed to determine the specific effects of COVID-19 on the risk of ATE or VTE in less severe forms of the disease.

Venous Thromboembolism in COVID-19: Are Women Different?

AbstractThe epidemiological data suggests predominant male prevalence, morbidity and mortality with SARS COVID-2. Similarly, venous thromboembolic (VTE) events have a male sex predilection with variant mechanisms involving angiotensin-converting enzyme 2 (ACE-2) expression and pathways in women. COVID-19 could directly affect or it could be an indirect action of the disease via critical ailment hypoxemia, or hemostatic abnormalities might be the underlying mechanisms of VTE in a COVID-19 patient with baseline risk factor profile. VTE diagnosis in a COVID scenario has issues of a prone positioned patient, exposure of health workers and minimal therapeutic benefits in a critically ill patient with acute respiratory distress syndrome (ARDS). Anticoagulation with low-molecular weight heparin (LMWH) can be chosen over unfractionated heparin (UFH) with less monitoring requirements and thereby low exposure to healthcare workers. Variant guidelines for thromboprophylaxis (in hospital/extended postdischarge) have come up, stating anticoagulant administration, according to baseline risk profile and hemostatic biomarkers. Catheter-directed interventions should be reserved only for life-threatening situations. In women, hormonal milieu (for e.g., 17 β-estradiol) might influence occurrence of favorable ACE 2 polymorphisms with less VTE events. The management strategies in a female patient with VTE would be more or less similar to males. Combined oral contraceptives (COC) and estrogen replacement therapies (ERT) may be curtailed in COVID-19 positive patients, given their thrombogenic potential. Pregnancy and postpartum state in COVID-19 positive patient need VTE prophylaxis all the more in the presence of risk profile favoring VTE. Also, VTE prophylaxis when indicated should be continued in women in a normal menstrual cycle. Bleeding risks specific to women (menorrhagia secondary to dysfunctional uterine bleeding [DUB], fibroids, adnexal malignancies and masses, hypothyroidism, etc.) need to be weighed while taking a decision for indicated anticoagulation regimen.

Pulmonary Thromboembolism in COVID-19: Proposal for a Scoring System for Diagnosis

The first of these studies demonstrated an increase in the incidence of PTE by comparing 107 patients with COVID-19 and 196 patients without COVID-19 admitted to an intensive care unit (ICU) from February 27 to March 31, 2020. The incidence of PTE in both groups was 20.6% and 6.1%, respectively.

Venous thromboembolism in COVID-19: systematic review of reported risks and current guidelines.

Many centres have noticed a high number of venous thromboembolism (VTE) events among critically ill inpatients with COVID-19 pneumonia. The aims of this study were (1) to summarise the reported risk of VTE associated with COVID-19 infections and (2) to summarise guidance documents on thromboprophylaxis in COVID-19 patients, in a systematic review. We systematically searched for peer-reviewed evidence on the risk of VTE in patients with COVID-19, in PubMed, Embase and Twitter, and for guidelines or guidance documents for thromboprophylaxis, from international or national societies relevant to the field of thrombosis and haemostasis, up to April 30 2020. We found 11 studies (1 clinical trial, 7 retrospective cohorts and 3 prospective cohorts), which included a range of 16 to 388 in patients with COVID-19 (total of 1369 inpatients). The diagnoses of COVID-19 and VTE were of high quality, but the follow-up was often unclear. Most studies reported universal in-hospital thromboprophylaxis. Among all inpatients and among intensive care unit (ICU) inpatients with COVID-19, reported risks of VTE were 4.4&ndash;8.2% (three studies) and 0&ndash;35.3% (six studies), respectively. Two studies at least partially screened for VTE in ICU inpatients with COVID-19, and found risks of 24.7&ndash;53.8%. We found 12 guidelines for thromboprophylaxis of COVID-19 patients. The majority suggested universal pharmacological thromboprophylaxis in all COVID-19 inpatients, but there was heterogeneity in the suggested intensity of thromboprophylaxis: seven advised considering intensified doses of heparin according to the clinical or biological severity of the disease, especially in the ICU setting. Venous thromboembolism very commonly complicates the clinical course of inpatients with COVID-19, despite thromboprophylaxis. The risk appears highest among critically ill inpatients. We found no estimates of risks among outpatients. Many questions remain unresolved, as delineated by the heterogeneity of national and international guidelines. This situation calls for fast randomised clinical trials, comparing different schemes of thromboprophylaxis in COVID-19 inpatients.

Antithrombotic Therapies in COVID-19 Disease: a Systematic Review.

BackgroundInfection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state.ObjectiveThis rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19.Data SourcesWe searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria.Study Selection, Data Extraction, and SynthesisOne investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking.ResultsIncidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes.ConclusionsNew evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.

Possible Mechanism and Current Recommendation of Thromboembolism in COVID-19

The coronavirus disease (COVID-19) has become a global pandemic with a high mortality rate. There has been emerging evidence regarding the presence of thrombosis in patients with severe COVID-19 infection. In addition, prognosis of COVID patients, once they are complicated with DVT or fatal pulmonary emboli, will also significantly decline. Hence, understanding the pathomechanism and prompt treatment of thromboembolism is important in improving the outcome in COVID-19 patients. Prophylaxis anticoagulant was proposed for all hospitalized COVID-19 patients. The aim of this article is to review the current literature regarding pathomechanism, risk assessment, diagnosis, and management of VTE.