# ent

id: cord-274542-fpzk5k79
type: GGP
entity:
  P2Y 12 receptor inhibitors lopinavir ritonavir and atazanavir reduce the antiplatelet effect of clopidogrel and prasugrel


id: cord-277146-4a4vz36h
type: ORG
entity:
  the Scientific Standardization Committee of the International Society on Thrombosis Haemostasis 2020 Scientific


id: cord-261629-ylajz928
type: ORG
entity:
  American College of Sports Medicine Resource Manual for Guidelines for Exercise Testing and Prescription


id: cord-306997-84pjfawk
type: GGP
entity:
  LDH p 0 04 and IL 6 p 0 04 were observed in VTE patients in comparison to non VTE patients In conclusion our findings showed a quite high prevalence of VTE in COVID 19 patients Raised inflammatory indexes and increased serum levels of pro inflammatory cytokines


id: cord-306997-84pjfawk
type: GGP
entity:
  CRP p 0 0001 r s 0 13392 or LDH p 0 0013 r s 0 05438 and it inversely correlated with MPV p 0 0001 r s 0 75608 MPV


id: cord-000728-ligqoj24
type: GGP
entity:
  sine kinase ZAP70 T cell surface antigens especially CD3 membrane surface immune receptor complex and T cell granzymes


id: cord-257939-tgpsd3r7
type: PROTEIN
entity:
  C reactive protein CRP 392 2 mg L lactic acid 1 1 mmol L serum sodium 135 mmol L serum potassium 5 2 mmol L


id: cord-301493-32l52q3s
type: PROTEIN
entity:
  ORCID profile K C 0000 0001 5139 6939 Correspondence Jason B Hill OMC NS Hospital Medicine Associate CMIO Ochsner Health System 100 Medical Center Dr Slidell LA 70460 e


id: cord-342603-k0f33p3l
type: ORG
entity:
  VTE Validation of Risk Assessment Models of Venous Thromboembolism in Hospitalized Medical Patients External


id: cord-283267-72wrzw09
type: ORG
entity:
  Improve Venous Thromboembolism Risk Stratification Validation of Risk Assessment Models of Venous Thromboembolism in Hospitalized Medical Patients External


id: cord-282636-u0ea02fc
type: WORK_OF_ART
entity:
  The Emerging Role of Neutrophil Extracellular Traps in Respiratory Disease Neutrophil Extracellular Traps


id: cord-353692-2zotqreu
type: WORK_OF_ART
entity:
  Hospitalized Patients Using a System wide Multifaceted Quality Improvement Intervention Rationale and Design


id: cord-353692-2zotqreu
type: ORG
entity:
  Chinese Prevention Strategy for Venous Thromboembolism Graduate School of Peking Union Medical College Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China 6 Department of information management Formal


id: cord-353692-2zotqreu
type: ORG
entity:
  Chinese Prevention Strategy for Venous Thromboembolism Graduate School of Peking Union Medical College Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China 6 Department


id: cord-328220-toeq4xq0
type: ORG
entity:
  Practical Considerations in Prevention and Treatment of Venous Thromboembolism in Hospitalized Patients


id: cord-328220-toeq4xq0
type: ORG
entity:
  Haemostasis of the Scientific and Standardization Committee of the International Society on Thrombosis


id: cord-339695-3ij5pjjy
type: WORK_OF_ART
entity:
  Thrombotic or Thromboembolic Disease Implications for Prevention Antithrombotic Therapy and Follow up Prevention Diagnosis and Treatment of VTE in Patients With COVID 19 CHEST Guideline and Expert Panel Report Total of patients


id: cord-336000-v88bq4bx
type: ORG
entity:
  the Uniform Requirements for Manuscripts Submitted to Biomedical Journals www icmje org October 2008


id: cord-336000-v88bq4bx
type: ORG
entity:
  Subcommittee on Control of Anticoagulation of the S Standardization Committee of the International Society on T Haemostasis Definition


id: cord-006870-f5w6fw6q
type: DISEASE
entity:
  pneumonia venous thromboembolism pulmonary embolism sepsis septic shock pulmonary edema gastrointestinal bleeding


id: cord-009997-oecpqf1j
type: DNA
entity:
  t 12 21 p13 q22 11q23 rearrangements KMT2A iAmp21 t 1 19 q23 p13 1 t 9 22 q34 q11 hypodiploidy hyperdiploidy


id: cord-009997-oecpqf1j
type: CELL_LINE
entity:
  California San Diego La Jolla California United States Background Clinical outcomes after allogeneic hematopoietic stem cell transplantation HSCT


id: cord-009997-oecpqf1j
type: GGP
entity:
  Asmaa Salama Eman D El Desouky Lobna Shalaby National Cancer Institute Cairo Cairo Egypt Background Hodgkin lymphoma HL


id: cord-009997-oecpqf1j
type: ORG
entity:
  the SIOP International Society of Paediatric Oncology PODC Paediatric Oncology in Developing Countries Abandonment of Treatment Working Group


id: cord-009997-oecpqf1j
type: WORK_OF_ART
entity:
  OS Children s Mercy Hospital Kansas City Kansas City Missouri United States Background Post Consolidation


id: cord-009997-oecpqf1j
type: DISEASE
entity:
  B cell lymphoma posttransplant lymphoproliferative disease Wilms tumor rhabdomyosarcoma Ewings sarcoma osteosarcoma neuroblastoma


id: cord-009997-oecpqf1j
type: DISEASE
entity:
  rhabdomyosarcoma RMS n 2 alveolar histology primary site nasopharynx n 1 and lower extremity n 1 Ewing s sarcoma


# bib

id: cord-000716-fhm8abxp
title: Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics
author: Wang, Hao
date: 2012-07-11
txt: ./txt/cord-000716-fhm8abxp.txt
cache: ./cache/cord-000716-fhm8abxp.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399218/
doi: 10.7150/ijms.4641
summary:
  BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE). Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. However, mRNA expression of P-selectin (mainly distributed on the surface of ECs and platelets) and E-selection (mainly distributed on the surface of activated ECs) are not elevated in PE group which indicate venous endothelial cells are not impaired in patients with PE (Fig.2) . Gene ontology analysis exhibited compromised T cell mediated immune function, and t test indicated associated genes were significantly down-regulated in patients with PE than in control groups. Two genes with down-regulated expressions are closely related to the T cell mediated immunity according to GO analysis (with high value of Enrichment). Patient outcomes after deep vein thrombosis and pulmonary embolism: the Worcester Venous Thromboembolism Study

abstract:
  BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE). METHODS: Twenty patients with PE and 20 age and gender matched patients without PE as controls were enrolled into the present study in the same period. The diagnosis of PE was based on the clinical manifestations and findings on imaging examinations. Acute arterial and/or venous thrombosis was excluded in controls. The whole human genome oligo microarray was employed for detection. Statistical analysis was performed with t test following analysis of very small samples of repeated measurements and Gene Ontology (GO) analysis. RESULTS: Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity. CONCLUSION: The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated. Genomic results may provide a new clue for clinical diagnosis, treatment and prevention of VTE.


id: cord-000728-ligqoj24
title: Symptomatic Venous Thromboembolism Is a Disease Related to Infection and Immune Dysfunction
author: Duan, Qianglin
date: 2012-07-26
txt: ./txt/cord-000728-ligqoj24.txt
cache: ./cache/cord-000728-ligqoj24.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410365/
doi: 10.7150/ijms.4453
summary:
  The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE. In addition, in 2010, we detected virus-like microorganisms in the lymphocytes of a young pulmonary hypertension patient with increased D-Dimer, which morphologically confirmed the attack of T cells by virus, and peripheral decreased CD3 + and CD8 + level also indicated virus infection caused significantly compromised function of T cells (10) . In addition, flow cytometry was performed to investigate the changes in immune cells in VTE patients, which aimed to validate the results from genome analysis. The Go analysis of the genomic study targeted the decreased immune function of T cells and immune receptor complex in PE patients, suggesting the occurrence of PE is closely related to the immune dysfunction.

abstract:
  The characteristics of human genomics and cellular immune function between clinically symptomatic venous thromboembolism (VTE) and controls were systematically compared to explore the immunologic pathogenesis of VTE. Microarray assay showed the mRNA expressions of genes related to non-specific cellarer immune and cytokines were significantly down-regulated. Abnormal expressions of CD3+, CD4+, CD8+, NK marker CD16+56+, CD19 and aberrant CD4+/CD8+ ratio were detected in 54 among 56 patients. In PE patients, microarray assay revealed the imbalance in the expressions of genes related to the immune system. The expressions of genes related to non-specific immune cells and cytokines were markedly up-regulated and those associated with cellular immune were dramatically down-regulated. In VTE patients, cytological examination indicated the functions of NK cells were significantly compromised, and the antigen recognition and killing function of T cells markedly decreased. The consistence between genomic and cytological examination suggests the symptomatic VTE is closely associated with the infection and immune dysfunction.


id: cord-006870-f5w6fw6q
title: Abstracts Presented at the Neurocritical Care Society (NCS) 15th Annual Meeting
author: nan
date: 2017-09-19
txt: ./txt/cord-006870-f5w6fw6q.txt
cache: ./cache/cord-006870-f5w6fw6q.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103238/
doi: 10.1007/s12028-017-0465-9
abstract: nan
summary:
  Subjective perceptions of recovery were assessed via responses to the forced-choice dichotomized question, "Do you feel that you have made a complete recovery from the arrest?"Objective outcome measures of recovery included: Repeatable Battery for Neuropsychological Status (RBANS), Modified Lawton Physical Self-Maintenance Scale (L-ADL), Barthel Index (BI), Cerebral Performance Category Scale (CPC), Center for Epidemiological Studies-Depression scale (CES-D), and Post traumatic stress disorder-checklist (PTSD-C). Utilizing data from the Citicoline Brain Injury Treatment (COBRIT) trial, a prospective multicenter study, we identified 224 patients who met the inclusion criteria; 1) placement of an ICP monitoring device, 2) Glasgow coma score (GCS) less than 9, 3) EVD placement prior to arrival or within 6 hours of arrival at the study institution. The objective of this study was to examine the incidence rates of pre-specified medical and neurological ICU complications, and their impact on post-traumatic in-hospital mortality and 12month functional outcomes.


id: cord-009997-oecpqf1j
title: 2018 ASPHO ABSTRACTS
author: nan
date: 2018-03-31
txt: ./txt/cord-009997-oecpqf1j.txt
cache: ./cache/cord-009997-oecpqf1j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167873/
doi: 10.1002/pbc.27057
abstract: nan
summary:
  Completed cranial radiation and proceeded to allogeneic stem cell transplant with unrelated cord marrow donor and is disease free at approximately day +200.Case 2: 5 year-old female diagnosed with FLT3 and MLL negative AML and completed treatment per COG AAML1031 study on the low risk arm without Bortezomib. Design/Method: This study was a retrospective chart review that included patients 3 to 23 years old with sickle cell disease type SS and S 0 followed at St. Christopher''s Hospital for Children. Background: Hydroxyurea, chronic blood transfusion, and bone marrow transplantation can reduce complications, and improve survival in sickle cell disease (SCD), but are associated with a significant decisional dilemma because of the inherent risk-benefit tradeoffs, and the lack of comparative studies. Brown University -Hasbro Children''s Hospital, Providence, Rhode Island, United States Background: Despite clinical advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant source of disease-related morbidity.


id: cord-257939-tgpsd3r7
author: Haider, Maryam B.
date: 2020-07-20
txt: ./txt/cord-257939-tgpsd3r7.txt
cache: ./cache/cord-257939-tgpsd3r7.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.12659/ajcr.925794
doi: 10.12659/ajcr.925794
summary:
  title: A 46-Year-Old Woman Who Presented with Diabetic Ketoacidosis and COVID-19 Pneumonia with Multiple Pulmonary Thromboemboli: A Case Report Patient: Female, 46-year-old Final Diagnosis: COVID provoked thromboembolism Symptoms: Cough • dyspnea Medication:— Clinical Procedure: — Specialty: Infectious Diseases • General and Internal Medicine OBJECTIVE: Unknown ethiology BACKGROUND: Coronavirus disease 2019 (COVID-19) occurs because of a novel enveloped ribonucleic acid coronavirus called severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2). Here we describe a case of COVID-19 provoked pulmonary embolism in a young patient already receiving prophylactic treatment for VTE. CONCLUSIONS: The finding of the case suggested that low-molecular-weight heparin prophylaxis may not be sufficient to prevent VTE in COVID-19 pneumonia. Here, we describe a case of COVID-19 that provoked PE in a young patient already receiving prophylactic treatment of venous thromboembolism (VTE). The findings of the case suggested that low-molecular-weight heparin prophylaxis may not be sufficient to prevent VTE in COVID-19 patients with proinflammatory state.

title:
  A 46-Year-Old Woman Who Presented with Diabetic Ketoacidosis and COVID-19 Pneumonia with Multiple Pulmonary Thromboemboli: A Case Report

abstract:
  Patient: Female, 46-year-old Final Diagnosis: COVID provoked thromboembolism Symptoms: Cough • dyspnea Medication:— Clinical Procedure: — Specialty: Infectious Diseases • General and Internal Medicine OBJECTIVE: Unknown ethiology BACKGROUND: Coronavirus disease 2019 (COVID-19) occurs because of a novel enveloped ribonucleic acid coronavirus called severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2). One of the major reported complications of COVID-19 includes both arterial and venous thromboembolism (VTE). Here we describe a case of COVID-19 provoked pulmonary embolism in a young patient already receiving prophylactic treatment for VTE. CASE REPORT: A 46-year-old female with past medical history of diabetes mellites, hypertension, and asthma presented in the emergency department (ED) with dyspnea requiring 6 liters per minute of oxygen on presentation. Her main complaints were cough and vomiting. In the ED, hypoxemia worsened, and she ultimately required endotracheal intubation. Labs were suggestive of diabetic ketoacidosis (DKA) and showed increase in all inflammatory markers and absolute lymphocytopenia. Chest X-ray showed bilateral diffuse patchy airspace opacities. Standard DKA management was started. She was also started on ceftriaxone, azithromycin, hydroxychloroquine, and subcutaneous heparin (5000 U every 8 h) for VTE prophylaxis. SARS-Cov2 reverse transcription-polymerase chain reaction returned positive. Ceftriaxone and azithromycin were discontinued the very next day because of low suspicion of bacterial infection while hydroxychloroquine was completed for 5 days. On the third day of admission, the patient self-extubated and was immediately placed on nonrebreather with spO(2) in low 90s. On the fourth day of admission, D-dimer came back 4.74 mg/L, which was elevated from a prior value, so computed tomography angiography of the lungs was done, which disclosed multiple emboli in the lungs. She was started on therapeutic doses of enoxaparin sodium, which was continued through her admission. She was switched to Apixaban on discharge. CONCLUSIONS: The finding of the case suggested that low-molecular-weight heparin prophylaxis may not be sufficient to prevent VTE in COVID-19 pneumonia. Some of these patients may benefit from receiving prophylactic half doses or full doses of anticoagulants.


id: cord-261629-ylajz928
author: Demirci, Ufuk
date: 2020-07-10
txt: ./txt/cord-261629-ylajz928.txt
cache: ./cache/cord-261629-ylajz928.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1177/1076029620933947
doi: 10.1177/1076029620933947
abstract: nan
summary:
  title: Reducing the Risk of Venous Thrombosis During Self-Isolation and COVID-19 Pandemic for Patients With Cancer: Focus on Home Exercises Prescription Recent studies have demonstrated that active ankle dorsiflexion, plantar flexion, subtalar inversion, and eversion exercises increase venous return in the lower extremity, which suggest that combination of these exercises will be effective to reduce and even prevent the stasis and so forth, VTE. 4 According to the American Society of Hematology 2019 guidelines for management of VTE, it is appropriate to use compression stocks in acutely or critically ill patients, who are not appropriate for anticoagulant prophylaxis because of bleeding risk. In conclusion, we recommend all caregivers to include a reasonable yet effective prescription of home exercise for all patients with malignancies. Ufuk Demirci https://orcid.org/0000-0001-6923-1470 Elif G. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update

title:
  Reducing the Risk of Venous Thrombosis During Self-Isolation and COVID-19 Pandemic for Patients With Cancer: Focus on Home Exercises Prescription


id: cord-262125-0vajpo98
author: Doyle, Andrew J.
date: 2020-10-08
txt: ./txt/cord-262125-0vajpo98.txt
cache: ./cache/cord-262125-0vajpo98.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.thromres.2020.10.007
doi: 10.1016/j.thromres.2020.10.007
abstract: nan
summary:
  title: Updated hospital associated venous thromboembolism outcomes with 90-days follow-up after hospitalisation for severe COVID-19 in two UK critical care units Hospitalisation with COVID-19 infection has been associated with an increased incidence of thrombosis, particularly in the critical care setting. Our two centres have previously described the early in-patient incidence of venous thromboembolism (VTE) at the peak of the COVID-19 outbreak in the United Kingdom1,2. The risk of hospital-associated VTE (HAT) for patients has been shown to extend from admission to 90 days following discharge with an early peak within the first weeks of this period3. We conducted an observational study of our previous cohorts with a minimum of 90 days follow-up from their critical care admission at our centres. The estimated cumulative incidence of VTE over a minimum of 90 days following critical care admission was 18.6% shown in Figure 1 (a) (95% confidence interval 12.4-25.8). Post-discharge venous thromboembolism following hospital admission with COVID-19

title:
  Updated hospital associated venous thromboembolism outcomes with 90-days follow-up after hospitalisation for severe COVID-19 in two UK critical care units


id: cord-274542-fpzk5k79
author: Patti, Giuseppe
date: 2020-11-03
txt: ./txt/cord-274542-fpzk5k79.txt
cache: ./cache/cord-274542-fpzk5k79.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s40256-020-00446-6
doi: 10.1007/s40256-020-00446-6
summary:
  UFH should be limited to patients with CrCl < 30 mL/min An invasive "catheter"-based therapy for PE is indicated in selected cases with contraindication to anticoagulant drugs, recurrent events despite adequate anticoagulation, or when systemic fibrinolysis cannot be performed For the risk stratification of patients with VTE, monitoring of the following parameters is useful: troponin, BNP, D-dimer, blood cell count, fibrinogen, prothrombin time, activated partial thromboplastin time, and degradation products of fibrin After the initial approach, DOACs may represent an option for in-hospital treatment of a VTE episode in patients with clinical stability and decreasing inflammation After a VTE episode, DOACs should represent the therapy of choice at discharge The use of imaging techniques in diagnosing a VTE episode is complex, because of the risk of viral transmission to other patients and to healthcare workers, and must be regulated by specific in-hospital protocols aimed at limiting such risk.

title:
  Questions and Answers on Practical Thrombotic Issues in SARS-CoV-2 Infection: A Guidance Document from the Italian Working Group on Atherosclerosis, Thrombosis and Vascular Biology

abstract:
  In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk–benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.


id: cord-277146-4a4vz36h
title: Hemostatic Abnormalities in COVID-19: An Update
author: Aggarwal, Mukul
date: 2020-08-11
txt: ./txt/cord-277146-4a4vz36h.txt
cache: ./cache/cord-277146-4a4vz36h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32837053/
doi: 10.1007/s12288-020-01328-2
summary:
  Multiple reports have reported the presence of deranged parameters of coagulation in patients of In this review, we will discuss the various pathophysiological mechanisms leading to COVID-19 associated coagulopathy (CAC), derangement in laboratory parameters, incidence, and risk factors of venous thromboembolism (VTE) and prevention and treatment of CAC. Pulmonary Intravascular Coagulation, its Histopathological Evidence and Contribution of Cytokine Storm COVID-19 patients have been shown to have high levels of D-dimer [8, 9] but unlike patients of sepsis, they only have a mild prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT), mild thrombocytopenia [4, 9] . They recommend standard dose LMWH as most preferred agent followed by UFH then DOAC for acutely ill and critical hospitalized patients with COVID-19. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

abstract:
  COVID-19 has emerged as a pandemic with lung being the primarily afflicted organ. Deranged hemostasis has been observed in patients with COVID-19 with scales tipped towards a prothrombotic state. The pathogenesis differs from disseminated intravascular coagulation with a primary pulmonary localization. This is referred to as pulmonary intravascular coagulopathy with strong component of thrombo-inflammation. This is reflected in the lab tests with an increase in D-dimer which correlates with severity and outcomes of disease. Common coagulation tests such as prothrombin time, activated partial thromboplastin time are only mildly prolonged while most patients have normal to increased fibrinogen and marginal thrombocytopenia. Overall, the patients have an increase in venous and arterial thrombotic events especially in ICU patients. Routine thromboprophylaxis with low molecular weight heparin is recommended in all hospitalized patients to reduce the incidence of thrombosis. Bleeding is uncommon and treated with blood products transfusion. This review shall discuss the hemostatic abnormalities in COVID-19 patients and their impact on prognosis. In addition, strategy of thromboprophylaxis and various academic society guidelines are discussed in detail.


id: cord-277201-jzjxsetx
title: More than Just Pneumonia: Acute Pulmonary Embolism in Two Middle-Aged Patients with COVID-19
author: Mazo, Jahinover
date: 2020-07-30
txt: ./txt/cord-277201-jzjxsetx.txt
cache: ./cache/cord-277201-jzjxsetx.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1155/2020/4812036
doi: 10.1155/2020/4812036
summary:
  We suspect that a prothrombotic inflammatory response provoked by coronavirus disease could be the culprit, acting as an additive effect on middle-aged patients with known risk factors for venous thromboembolism. In addition to coagulation factor abnormalities, other reported findings of increased D-dimers, ferritin, and lactate dehydrogenase further support the assertion that a prothrombotic response to the virus is driving the thromboembolic events among COVID-19 patients [9] . Severe COVID-19 infections have also been associated with an inflammatory prothrombotic state, also potentially playing a key role behind the increase in reported thromboembolic complications. We suspect that the existing risk factors present along with the superimposed prothrombotic state induced by COVID-19 induced inflammatory response may have precipitated the development of the venous thromboembolism resulting in PE. e CHEST Guideline and Expert Panel Report on management of venous thromboembolism (VTE) in COVID-19 patients outlines various recommendations for management of acute VTE.

abstract:
  BACKGROUND: Although severe pneumonia and respiratory compromise have remained the predominant complications of coronavirus disease 19, we are now learning this virus is much more varied in its presentation. In particular, there are increasingly reported cases of thromboembolic events occurring in infected patients. Case Report. In this report, we present two patients, both under the age of 40 with known risk factors for venous thromboembolism, who presented with respiratory distress. Both patients were diagnosed with SARS-CoV-2 pneumonia and pulmonary embolism requiring management with anticoagulation. Both patients were discharged after a short course in the hospital. CONCLUSION: The discussion of a hypercoagulable state induced by coronavirus disease 19 has been well documented; however, the exact mechanisms remain unknown. We suspect that a prothrombotic inflammatory response provoked by coronavirus disease could be the culprit, acting as an additive effect on middle-aged patients with known risk factors for venous thromboembolism. We recommend clinicians closely monitor those with known risk factors for pulmonary embolism.


id: cord-282636-u0ea02fc
title: Neutrophil extracellular traps and thrombosis in COVID-19
author: Zuo, Y.
date: 2020-05-05
txt: ./txt/cord-282636-u0ea02fc.txt
cache: ./cache/cord-282636-u0ea02fc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32511553/
doi: 10.1101/2020.04.30.20086736
summary:
  For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19. Neutrophil-derived neutrophil extracellular traps (NETs) play a pathogenic role in many thrombo-inflammatory states including sepsis 4, 5 , thrombosis [6] [7] [8] , and respiratory failure 9, 10 . We identified four patients admitted to a large academic medical center with COVID-19 who also developed VTE (either deep vein thrombosis or pulmonary embolism) despite immediate initiation of prophylactic-dose heparin. 30.20086736 doi: medRxiv preprint elevated by the time the patient was diagnosed with deep vein thrombosis on day 20 ( Table 2) . Vivo Role of Neutrophil Extracellular Traps in Antiphospholipid Antibody-Mediated Venous Thrombosis

abstract:
  Here, we report on four patients whose hospitalizations for COVID-19 were complicated by venous thromboembolism (VTE). All demonstrated high levels of D-dimer as well as high neutrophil-to-lymphocyte ratios. For three patients, we were able to test sera for neutrophil extracellular trap (NET) remnants and found significantly elevated levels of cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3. Neutrophil-derived S100A8/A9 (calprotectin) was also elevated. Given strong links between hyperactive neutrophils, NET release, and thrombosis in many inflammatory diseases, the potential relationship between NETs and VTE should be further investigated in COVID-19.


id: cord-283267-72wrzw09
author: Moores, Lisa K.
date: 2020-06-02
txt: ./txt/cord-283267-72wrzw09.txt
cache: ./cache/cord-283267-72wrzw09.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32502594/
doi: 10.1016/j.chest.2020.05.559
summary:
  The recognition of the coagulopathy with COVID-19, and the early evidence that suggests that thrombosis in these patients is higher than that seen in similarly ill hospitalized patients with other respiratory infections has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. 19 Pooled risk estimates for benefits and harms of anticoagulant thromboprophylaxis in critically ill medical patients without COVID-19 differ across meta-analyses, 19, 22, 46 but practice guidelines consistently recommend anticoagulant thromboprophylaxis with LMWH (or unfractionated heparin [UFH]) over no such therapy. Our literature search did not identify any randomized trials assessing the efficacy and safety of anticoagulants for the treatment of acute VTE in hospitalized or critically ill COVID-19 patients. Our literature search did not identify any randomized trials or prospective cohort studies assessing the efficacy or safety of any thrombolytic therapies for the management of critically ill patients with COVID-19 without objective evidence of VTE and VTE-associated hypotension.

title:
  Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report

abstract:
  Abstract: Background Emerging evidence shows that severe COVID-19 can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and venous thromboembolism (VTE). This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE. Methods A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19. MEDLINE (via PubMed or Ovid), Embase and Cochrane Controlled Register of Trials were systematically searched for relevant literature and references were screened for inclusion. Validated evaluation tools were used to grade the level of evidence to support each recommendation. When evidence did not exist, guidance was developed based on consensus using the modified Delphi process. Results The systematic review and critical analysis of the literature based on13 PICO questions resulted in 22 statements. Very little evidence exists in the COVID-19 population. The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements. Conclusions The evidence on the optimal strategies to prevent, diagnose, and treat venous thromboembolism in patients with COVID-19 is sparse, but rapidly evolving.


id: cord-288626-7bp92xyo
author: Spyropoulos, Alex C.
date: 2020-06-30
txt: ./txt/cord-288626-7bp92xyo.txt
cache: ./cache/cord-288626-7bp92xyo.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0735109720352293
doi: 10.1016/j.jacc.2020.04.071
summary:
  OBJECTIVES: The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge. The lower 7.5 mg dose of rivaroxaban used in patients with moderate renal insufficiency was found to be ineffective (8) A meta-analysis of arterial thrombosis (including MI and ischemic stroke) of older studies involving w11,000 medically ill inpatients receiving heparinbased prophylaxis did not find a reduction of these events compared with control subjects (odds ratio: On-treatment includes all data from randomization to 2 days after the last dose of the study drug (inclusive). Our analysis suggests that in at-risk medically ill patients who are discharged from the hospital, extended-duration rivaroxaban at the 10 mg daily dose leads to a significant risk reduction in a composite of fatal and major thromboembolic eventsincluding symptomatic VTE, MI, nonhemorrhagic stroke, and CV death-without a significant increase in major bleeding, compared with placebo.

title:
  Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill Patients

abstract:
  BACKGROUND: Hospitalized acutely ill medical patients are at risk for fatal and major thromboembolic events. Whether use of extended-duration primary thromboprophylaxis can prevent such events is unknown. OBJECTIVES: The purpose of this study was to evaluate whether extended-duration rivaroxaban reduces the risk of venous and arterial fatal and major thromboembolic events without significantly increasing major bleeding in acutely ill medical patients after discharge. METHODS: MARINER (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients) studied acutely ill medical patients with additional risk factors for venous thromboembolism (VTE). Medically ill patients with a baseline creatinine clearance ≥50 ml/min were randomized in a double-blind fashion to rivaroxaban 10 mg or placebo daily at hospital discharge for 45 days. Exploratory efficacy analyses were performed with the intent-to-treat population including all data through day 45. Time-to-event curves were calculated using the Kaplan-Meier method. A blinded independent committee adjudicated all clinical events. RESULTS: In total, 4,909 patients were assigned to rivaroxaban and 4,913 patients to placebo. The mean age was 67.8 years, 55.5% were men, mean baseline creatinine clearance was 87.8 ml/min, and mean duration of hospitalization was 6.7 days. The pre-specified composite efficacy endpoint (symptomatic VTE, myocardial infarction, nonhemorrhagic stroke, and cardiovascular death) occurred in 1.28% and 1.77% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 0.72; 95% confidence interval: 0.52 to 1.00; p = 0.049), whereas major bleeding occurred in 0.27% and 0.18% of patients in the rivaroxaban and placebo groups, respectively (hazard ratio: 1.44; 95% confidence interval: 0.62 to 3.37; p = 0.398). CONCLUSIONS: Extended-duration rivaroxaban in hospitalized medically ill patients resulted in a 28% reduction in fatal and major thromboembolic events without a significant increase in major bleeding. (A Study of Rivaroxaban [JNJ-39039039] on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients [MARINER]; NCT02111564)


id: cord-291483-ni6toh8c
title: A Review of Venous Thromboembolism Phenomena in COVID-19 Patients
author: Kermani-Alghoraishi, Mohammad
date: 2020-08-28
txt: ./txt/cord-291483-ni6toh8c.txt
cache: ./cache/cord-291483-ni6toh8c.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.cpcardiol.2020.100692
doi: 10.1016/j.cpcardiol.2020.100692
summary:
  One of the most important known complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the occurrence of venous thromboembolic (VTE) events, especially in critically ill patients and hospitalized in the intensive care unit. Diagnosis of VTE disease, especially pulmonary embolism, in patients with SARS-CoV 2 infections are incredibly difficult and challenging. As the first para-clinical approach in the diagnostic algorithm of pulmonary embolism, the use of D-dimer in the patients admitted with SARS-CoV 2 infection is controversial, because this marker has been increased as an acute reaction factor in hospitalized patients in need of respiratory care and loses its predictive value due to its low specificity (28) . Finally, according to recent studies, it is recommended that most of the hospitalized COVID-19 patients, especially critically ill patients admitted to ICU or cases with high D-dimer level, use pharmacological VTE prophylaxis (23, 37) .

abstract:
  With the outbreak of the second peak of COVID-19 in many countries of the world, re-attention to the symptoms and complications of this disease has received much attention. One of the most important known complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the occurrence of venous thromboembolic (VTE) events, especially in critically ill patients and hospitalized in the intensive care unit. The pathology of this event is complex and multifactorial, but the main problem now is the timely diagnosis of these phenomena, which can reduce the mortality and morbidity of patients. Deterioration of clinical condition in patients with SARS-CoV-2 infection along with increased coagulation markers can increase clinical suspicion of VTE events. Imaging techniques, especially computed tomography pulmonary angiography, can well solve this puzzle and lead to timely treatment of these patients.


id: cord-296607-h2zwlyz7
author: Watson, Ryan A.
date: 2020-06-09
txt: ./txt/cord-296607-h2zwlyz7.txt
cache: ./cache/cord-296607-h2zwlyz7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32429774/
doi: 10.1080/21548331.2020.1772639
summary:
  What is clear is that patients appear to be at higher risk for thrombotic disease states including acute coronary syndrome (ACS), venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE), or stroke. In most scenarios, direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin due to large randomized controlled trials showing noninferiority or superiority for stroke reduction and superiority for bleeding risk in patients with non-valvular atrial fibrillation [29] [30] [31] [32] . The use of UFH or LMWH may be considered in patients with high potential stroke risk and new onset atrial fibrillation; however, heparin drips require constant monitoring and titration of dosing during hospitalization leading to increased nursing exposure to potential COVID-19 patients. A French cohort of ICU patients on pharmacologic prophylaxis found a high prevalence of thrombotic complications including PE, stroke, circuit clotting of continuous renal replacement therapy or extracorporeal membrane oxygenation (ECMO) with minimal bleeding risk suggesting the need for higher doses of prophylactic anticoagulation in this patient population [70] .

title:
  Anti-coagulant and anti-platelet therapy in the COVID-19 patient: a best practices quality initiative across a large health system

abstract:
  The coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged health-care systems and physicians worldwide to attempt to provide the best care to their patients with an evolving understanding of this unique pathogen. This disease and its worldwide impact have sparked tremendous interest in the epidemiology, pathogenesis, and clinical consequences of COVID-19. This accumulating body of evidence has centered around case series and often empiric therapies as controlled trials are just getting underway. What is clear is that patients appear to be at higher risk for thrombotic disease states including acute coronary syndrome (ACS), venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE), or stroke. Patients with underlying cardiovascular disease are also at higher risk for morbidity and mortality if infected. These patients are commonly treated with anticoagulation and/or antiplatelet medications and less commonly thrombolysis during hospitalization, potentially with great benefit but the management of these medications can be difficult in potentially critically ill patients. In an effort to align practice patterns across a large health system (Jefferson Health 2,622 staffed inpatient beds and 319 intensive care unit (ICU) beds across 14 facilities), a task force was assembled to address the utilization of anti-thrombotic and anti-platelet therapy in COVID-19 positive or suspected patients. The task force incorporated experts in Cardiology, Vascular Medicine, Hematology, Vascular Surgery, Pharmacy, and Vascular Neurology. Current guidelines, consensus documents, and policy documents from specialty organizations were used to formulate health system recommendations. OBJECTIVE: Our goal is to provide guidance to the utilization of antithrombotic and antiplatelet therapies in patients with known or suspected COVID-19.


id: cord-297001-4g3wb8qi
title: Venous Thromboembolism Complicated with COVID-19: What Do We Know So Far?
author: Tal, Shir
date: 2020-05-12
txt: ./txt/cord-297001-4g3wb8qi.txt
cache: ./cache/cord-297001-4g3wb8qi.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1159/000508233
doi: 10.1159/000508233
summary:
  Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease. However, many of the COVID-19 patients may present with high levels of D-dimer due to other causes -inflammation, disseminated intravascular coagulation, advanced age, or infection [23] suggesting the need for CTPA as an initial rule-out test as well. Finally, based on the correlation between high levels of D-dimer and severe COVID-19 disease [7, 37] as well as higher mortality rate [5, 38] , the International Society on Thrombosis and Haemosthasis (ISTH) and American Society of Hematology (ASH) guidelines [39] advises prophylactic LMWH in all hospitalized COVID-19 patients in the absence of any contraindications (active bleeding and platelet count less than 25 × 10 9 /L) [34, 40] .

abstract:
  Coronavirus disease (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is responsible for the ongoing 2019–2020 pandemic. Venous thromboembolism (VTE), a frequent cardiovascular and/or respiratory complication among hospitalized patients, is one of the known sequelae of the illness. Hospitalized COVID-19 patients are often elderly, immobile, and show signs of coagulopathy. Therefore, it is reasonable to assume a high incidence of VTE among these patients. Presently, the incidence of VTE is estimated at around 25% of patients hospitalized in the intensive care unit for COVID-19 even under anticoagulant treatment at prophylactic doses. In this review, we discuss present knowledge of the topic, the unique challenges of diagnosis and treatment of VTE, as well as some of the potential mechanisms of increased risk for VTE during the illness. Understanding the true impact of VTE on patients with COVID-19 will potentially improve our ability to reach a timely diagnosis and initiate proper treatment, mitigating the risk for this susceptible population during a complicated disease.


id: cord-301493-32l52q3s
title: Frequency of venous thromboembolism in 6513 patients with COVID-19: a retrospective study
author: Hill, Jason B.
date: 2020-11-02
txt: ./txt/cord-301493-32l52q3s.txt
cache: ./cache/cord-301493-32l52q3s.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1182/bloodadvances.2020003083
doi: 10.1182/bloodadvances.2020003083
summary:
  From this cohort, patients with confirmed VTE (either during or after their hospital encounter) were identified by administrative query of the EHR.: Between 1 March 2020 and 1 May 2020, 6153 patients with COVID-19 were identified; 2748 of these patients were admitted, while 3405 received care exclusively through the emergency department. 7 To provide additional information about the association of VTE with COVID-19, we present a large retrospective cohort study examining all polymerase chain reaction-confirmed COVID-19 patients admitted to hospitals or treated in emergency departments affiliated with the Ochsner Health System. To estimate the rate of failure of VTE prophylaxis among COVID-19-positive hospitalized patients, we defined failure as any DVT or PE event diagnosed $3 days after the admission of a patient who had received $2 days of evidence-based mechanical or pharmacologic VTE prophylaxis immediately prior.

abstract:
  Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appear to be at increased risk for venous thromboembolism (VTE), especially if they become critically ill with COVID-19. Some centers have reported very high rates of thrombosis despite anticoagulant prophylaxis. The electronic health record (EHR) of a New Orleans–based health system was searched for all patients with polymerase chain reaction–confirmed SARS-CoV-2 infection who were either admitted to hospital or treated and discharged from an emergency department between 1 March 2020 and 1 May 2020. From this cohort, patients with confirmed VTE (either during or after their hospital encounter) were identified by administrative query of the EHR.: Between 1 March 2020 and 1 May 2020, 6153 patients with COVID-19 were identified; 2748 of these patients were admitted, while 3405 received care exclusively through the emergency department. In total, 637 patients required mechanical ventilation and 206 required renal replacement therapy. Within the hospitalized cohort, the overall mortality rate was 24.5% and VTE occurred in 86 patients (3.1%). In the 637 patients who required mechanical ventilation at some point during their hospital stay, 45 developed VTE (7.2%). After a median follow-up of 14.6 days, VTE had been diagnosed in 3 of the 2075 admitted who were discharged alive (0.14%). Among 6153 patients with COVID-19 who were hospitalized or treated in emergency departments, we did not find evidence of unusually high VTE risk. Pending further evidence from prospective, controlled trials, our findings support a traditional approach to primary VTE prevention in patients with COVID-19.


id: cord-306997-84pjfawk
author: Melazzini, Federica
date: 2020-11-08
txt: ./txt/cord-306997-84pjfawk.txt
cache: ./cache/cord-306997-84pjfawk.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11739-020-02550-6
doi: 10.1007/s11739-020-02550-6
summary:
  A number of pathogenic mechanisms have been hypothesized for VTE in COVID-19 patients, including active inflammation, immobilization and intensive care treatments, but the limited evidence available in the literature does not allow to estimate the relative contribution of each of the abovementioned factors [8] . Starting from these premises, we here aimed to define VTE rates and types, not considering peripheral and central catheter-related thrombosis, among a cohort of COVID-19 patients during their hospital stay at the San Matteo Hospital Foundation (Pavia, Northern Italy). We extracted data from medical records of all 259 consecutive patients with a diagnosis of COVID-19 admitted to the Departments of Internal Medicine, Infectious Disease, Intensive Care, and Respiratory Disease of the San Matteo Hospital Foundation (Pavia, Northern Italy), between March 19th and April 6th, 2020. We reviewed records of all 259 COVID-19 patients for demographic information, co-morbidities, risk factors for VTE according to the Padua prediction score [16] , laboratory tests and anticoagulation treatment at the time of hospital admission.

title:
  Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy

abstract:
  Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p < 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p < 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p < 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02550-6) contains supplementary material, which is available to authorized users.


id: cord-311622-fqptz6v3
title: Venous thromboembolism in COVID‐19 patients
author: Porfidia, Angelo
date: 2020-04-15
txt: ./txt/cord-311622-fqptz6v3.txt
cache: ./cache/cord-311622-fqptz6v3.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/jth.14842
doi: 10.1111/jth.14842
summary:
  We read with interest the study published by Tang and coll.(1) in a recent issue of the Journal of Thrombosis and Haemostasis. The definition of severe COVID‐19 was the presence of at least one of following: respiratory rate ≥30 breaths /min; arterial oxygen saturation ≤93% at rest; PaO2/FiO2 ≤300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D‐dimer levels. In this retrospective analysis, conducted at the Tongji Hospital of Wuhan, China, it is reported that heparin treatment reduces mortality in subjects affected by severe COVID-19 who have "sepsis-induced coagulopathy". The definition of severe COVID-19 was the presence of at least one of following: respiratory rate ≥30 breaths /min; arterial oxygen saturation ≤93% at rest; PaO2/FiO2 ≤300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D-dimer levels.

abstract:
  We read with interest the study published by Tang and coll.(1) in a recent issue of the Journal of Thrombosis and Haemostasis. In this retrospective analysis, conducted at the Tongji Hospital of Wuhan, China, it is reported that heparin treatment reduces mortality in subjects affected by severe COVID‐19 who have “sepsis‐induced coagulopathy”. The definition of severe COVID‐19 was the presence of at least one of following: respiratory rate ≥30 breaths /min; arterial oxygen saturation ≤93% at rest; PaO2/FiO2 ≤300 mmHg. The Authors of this study also reported that, among subjects not treated with heparin, mortality raised according with D‐dimer levels. Of note, patients that received heparin in this study were mostly treated with enoxaparin, at the thromboprophylactic dose of 40‐60 mg/day, for at least 7 days.


id: cord-312388-pc89ybxw
title: Current Overview on Hypercoagulability in COVID-19
author: Singhania, Namrata
date: 2020-08-04
txt: ./txt/cord-312388-pc89ybxw.txt
cache: ./cache/cord-312388-pc89ybxw.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32748336/
doi: 10.1007/s40256-020-00431-z
summary:
  ACE-2 angiotensin-converting enzyme 2, C4d complement 4d, C5b-9 complement 5b-9, COVID-19 coronavirus disease 2019, IL interleukin, K clot formation time, LY30 clot lysis at 30 min, MA maximum amplitude, MAC membrane attack complex, MASP2 mannose-binding proteinassociated serine protease 2, R reaction time, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, TEG thromboelastography, vWF von Willebrand factor showed small and firm thrombi in peripheral parenchyma [5] . Routine laboratory testing was performed in 24 critically ill COVID-19 patients and identified several abnormalities, including normal or slightly prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), normal or increased platelet count, and increased D-dimer and fibrinogen levels [12] . In a series of 184 patients (all patients receiving prophylactic anticoagulation) with severe COVID-19 and in the ICU, VTE was reported in 27% [16] ; the study was associated with a 13% mortality rate.

abstract:
  The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.


id: cord-313243-pwmi765q
title: Incidence of venous thromboembolism in hospitalized patients with COVID‐19
author: Middeldorp, Saskia
date: 2020-07-27
txt: ./txt/cord-313243-pwmi765q.txt
cache: ./cache/cord-313243-pwmi765q.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32369666/
doi: 10.1111/jth.14888
summary:
  OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19. CONCLUSIONS: The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. 1, 2 Additionally, more pronounced coagulation activation seems to be correlated with a severe disease course, including admission to the intensive care unit (ICU) and death. In a cohort of 81 ICU patients in China, in which routine thromboprophylaxis was not the standard of care, the proportion of patients who were diagnosed with DVT was 25%; a follow-up duration or cumulative incidence was not reported. The 3% risk of VTE among patients who were not admitted to ICU is considerable, despite the standard use of thrombosis prophylaxis. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis Incidence of venous thromboembolism in hospitalized patients with COVID-19

abstract:
  BACKGROUND: Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications. OBJECTIVES: To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19. METHODS: Single‐center cohort study of 198 hospitalized patients with COVID‐19. RESULTS: Seventy‐five patients (38%) were admitted to the intensive care unit (ICU). At time of data collection, 16 (8%) were still hospitalized and 19% had died. During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis. The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively. For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36). VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5). The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days). CONCLUSIONS: The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE. Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.


id: cord-314259-26jriik0
author: Pizzolo, Francesca
date: 2020-08-06
txt: ./txt/cord-314259-26jriik0.txt
cache: ./cache/cord-314259-26jriik0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0049384820304461
doi: 10.1016/j.thromres.2020.08.008
abstract: [Figure: see text]
summary:
  The prevalence of deep vein thrombosis (DVT) in patients hospitalized for SARS-CoV-2 infection remains, however, not well defined, especially for those admitted to COVID-19 Standard Care Units (SCU). Therefore, we designed a study with the aims of assessing the prevalence of DVT among subjects with SARS-CoV-2 pneumonia in the setting of SCU and investigating the clinical and laboratory characteristics associated with DVT in COVID-19 patients. The findings of a high prevalence of DVT in patients taking the usual thromboprophylaxis and estimated at low risk of thrombotic complications according to the traditional risk assessment model (such as the Padua Prediction Score), emphasize some unsolved issues: i) potential SARS-CoV-2-related hypercoagulable state, ii) appropriate VTE risk stratification for hospitalized COVID-19 patients, and iii) the choice of anticoagulant agents and relative doses, which require further investigations [2] .

title:
  Deep vein thrombosis in SARS-CoV-2 pneumonia-affected patients within standard care units: Exploring a submerged portion of the iceberg


id: cord-320822-etibcspx
title: Fibrinolysis Shutdown Correlates to Thromboembolic Events in Severe COVID-19 Infection
author: Wright, Franklin L.
date: 2020-05-15
txt: ./txt/cord-320822-etibcspx.txt
cache: ./cache/cord-320822-etibcspx.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1072751520304002
doi: 10.1016/j.jamcollsurg.2020.05.007
summary:
  CONCLUSIONS: Fibrinolysis shutdown, as evidenced by elevated D-Dimer and complete failure of clot lysis at 30 minutes on thromboelastography, predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. While not significant, thrombotic stroke rate was also increased from 7% to 30% (p=0.274 In the trauma population, hypercoagulable TEG parameters predict venous thromboembolism (VTE) 2.4 -6.7 fold higher based on higher maximum amplitude (MA) parameters despite appropriate prophylactic anticoagulation [16] [17] [18] [19] . Elevated D-dimer levels were also associated with potential micro-thrombotic disease leading to Recently, acute fibrinolysis shutdown has been demonstrated in early sepsis and found to correlate to increased morbidity and mortality 32 . A TEG LY30 of 0% and a D-dimer of greater than 2600 ng/ml together suggest complete fibrinolysis shutdown and markedly elevated risk of renal failure, VTE, and thrombotic events.

abstract:
  BACKGROUND: Coronavirus disease 2019 (COVID-19) predisposes patients to a prothrombotic state with demonstrated microvascular involvement. The degree of hypercoagulability appears to correlate with outcomes, however optimal criteria to assess for the highest risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography (TEG) measurements of coagulation would correlate with thromboembolic events. METHODS: Patients admitted to an intensive care unit with COVID-19 diagnoses that had TEG analyses performed were studied. Conventional coagulation assays, D-dimer levels, and viscoelastic parameters were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new onset renal failure. RESULTS: Forty-four patients with COVID-19 were included in the analysis. Derangements in coagulation laboratory values including elevated D-Dimer, fibrinogen, PT, and PTT were confirmed; viscoelastic parameters showed an elevated maximum amplitude and low lysis at 30 minutes. A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted VTE with an AUROC of .742 (p=0.021). A D-Dimer cutoff of 2600 ng/ml predicted need for dialysis with an AUROC of .779 (p=0.005). Overall, patients with no lysis of clot at 30 minutes and a D-Dimer of greater than 2600 ng/ml had a rate of VTE of 50% compared to 0% for patients with neither risk factor (p=0.008) and had a hemodialysis rate of 80% compared to 14% (p=0.004). CONCLUSIONS: Fibrinolysis shutdown, as evidenced by elevated D-Dimer and complete failure of clot lysis at 30 minutes on thromboelastography, predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19. Further clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.


id: cord-324245-cfiekxr4
author: Giorgi-Pierfranceschi, Matteo
date: 2020-08-25
txt: ./txt/cord-324245-cfiekxr4.txt
cache: ./cache/cord-324245-cfiekxr4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32840805/
doi: 10.1007/s11739-020-02472-3
summary:
  In a single-center cross-sectional study, all patients hospitalized for more than 5 days in Internal Medicine Department with confirmed COVID-19 pneumonia received 2-point compressive ultrasound assessment (CUS) of the leg vein system during a single day. Aim of our study was to evaluate the prevalence of deep vein thrombosis of the legs in a cohort of patients admitted to Internal Medicine of Cremona Hospital, with severe SARS-Cov-2 infection and treated with standard thromboprophylaxis, in a period between 5 and 10 days from hospitalization. The main demographic and clinical characteristics of the patients with DVT are shown in Table 2 Discussion Our study shows that in patients admitted to a hospital medical ward because of COVID-19-associated pneumonia, the prevalence of silent proximal DVT was as high as 13.6%, despite standard anticoagulant prophylaxis.

title:
  Prevalence of asymptomatic deep vein thrombosis in patients hospitalized with SARS-CoV-2 pneumonia: a cross-sectional study

abstract:
  The association between coronavirus disease 2019 (COVID-19) pneumonia and venous thrombotic disorders is still unclear. We assessed the association between COVID-19 infection-related pneumonia and proximal deep-vein thrombosis (DVT) in a cohort of patients admitted to our hospital during the European outbreak in the front line of Cremona, Lombardy. In a single-center cross-sectional study, all patients hospitalized for more than 5 days in Internal Medicine Department with confirmed COVID-19 pneumonia received 2-point compressive ultrasound assessment (CUS) of the leg vein system during a single day. Ninety-four percent of patients received enoxaparin as standard pharmacological prophylaxis for venous thromboembolism. The presence of DVT was defined as incompressibility of popliteal or common femoral vein. Out of 121 patients with COVID-19 pneumonia (mean age 71.8, 66.3% males) hospitalized on March 31st, 70 stayed in hospital for over 5 days and 66 of them underwent CUS of deep venous system of the legs. The presence of asymptomatic DVT was found in 9 patients (13.6%). No symptomatic DVT was found. Patients with DVT showed mean age = 75.7 years, mean D-dimer levels = 4.02 ng/ml and all of them received enoxaparin for thromboprophylaxis, except one. Computed tomography pulmonary angiogram confirmed pulmonary embolism in five patients. One every seven patients with COVID-19-related pneumonia, hospitalized for more than 5 days, had asymptomatic proximal DVT and half of them had confirmed PE despite standard pharmacological thromboprophylaxis. This observational study suggests the need of an active surveillance through CUS in patients hospitalized with acute SARS-COV-2 and underline the need of a more intense thromboprophylaxis.


id: cord-324265-j3v3i8vm
title: COVID-19, coagulopathy and venous thromboembolism: more questions than answers
author: Marietta, Marco
date: 2020-07-11
txt: ./txt/cord-324265-j3v3i8vm.txt
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mime: text/plain
url: https://doi.org/10.1007/s11739-020-02432-x
doi: 10.1007/s11739-020-02432-x
summary:
  The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. In these patients, low molecular weight heparin (LMWH) or unfractionated heparin (UFH) at doses registered for prevention of venous thromboembolism (VTE) seemed to be associated with a lower risk of death [10] and is currently recommended by the World Health Organization [11] and by several scientific societies [12] [13] [14] [15] [16] [17] [18] (Table 1) .

abstract:
  The acute respiratory illnesses caused by severe acquired respiratory syndrome corona Virus-2 (SARS-CoV-2) is a global health emergency, involving more than 8.6 million people worldwide with more than 450,000 deaths. Among the clinical manifestations of COVID-19, the disease that results from SARS-CoV-2 infection in humans, a prominent feature is a pro-thrombotic derangement of the hemostatic system, possibly representing a peculiar clinicopathologic manifestation of viral sepsis. The severity of the derangement of coagulation parameters in COVID-19 patients has been associated with a poor prognosis, and the use of low molecular weight heparin (LMWH) at doses registered for prevention of venous thromboembolism (VTE) has been endorsed by the World Health Organization and by Several Scientific societies. However, some relevant issues on the relationships between COVID-19, coagulopathy and VTE have yet to be fully elucidated. This review is particularly focused on four clinical questions: What is the incidence of VTE in COVID-19 patients? How do we frame the COVID-19 associated coagulopathy? Which role, if any, do antiphospolipid antibodies have? How do we tackle COVID-19 coagulopathy? In the complex scenario of an overwhelming pandemic, most everyday clinical decisions have to be taken without delay, although not yet supported by a sound scientific evidence. This review discusses the most recent findings of basic and clinical research about the COVID-associated coagulopathy, to foster a more thorough knowledge of the mechanisms underlying this compelling disease.


id: cord-326272-ya3r0h1t
title: Coagulopathy, Venous Thromboembolism, and Anticoagulation in Patients with COVID‐19
author: Dobesh, Paul P.
date: 2020-10-01
txt: ./txt/cord-326272-ya3r0h1t.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.1002/phar.2465
doi: 10.1002/phar.2465
summary:
  30 Other trials have evaluated VTE rates in CUS screened ICU patients with COVID-19 receiving pharmacologic prophylaxis with rates as high as 69% to 85%, which are higher than reported in typical ICU patients (Table 3) . Most hospitalized patients with COVID-19 are over age 40 years and have a number of risk factors for VTE, such as pneumonia, obesity, immobility, respiratory disease, elevated D-dimer levels, as well as potentially underlying heart failure, smoking, varicose veins, cancer, and previous VTE. 82 An observational cohort study of critically ill patients with severe ARDS from H1N1 viral pneumonia demonstrated that empiric systemic heparinization titrated to a goal heparin level of 0.3 -0.7 anti-Xa units/mL was significantly better at reducing VTE rates than standard prophylactic doses of either UFH or LMWH. 32 As discussed previously, a number of observational studies have reported higher than expected rates of VTE in critically ill patients with COVID-19, despite the use of standard dose anticoagulant prophylaxis.

abstract:
  Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)has led to a world‐wide pandemic, and patients with the infection are referred to as having COVID‐19. Although COVID‐19 is commonly considered a respiratory disease, there is clearly a thrombotic potential that was not expected. The pathophysiology of the disease and subsequent coagulopathy produce an inflammatory, hypercoagulable, and hypofibrinolytic state. Several observational studies have demonstrated surprisingly high rates of venous thromboembolism (VTE) in both general ward and intensive care patients with COVID‐19. Many of these observational studies demonstrate high rates of VTE despite patients being on standard, or even higher intensity, pharmacologic VTE prophylaxis. Fibrinolytic therapy has also been used in patients with acute respiratory distress syndrome. Unfortunately, high quality randomized controlled trials are lacking. A literature search was performed to provide the most up‐to‐date information on the pathophysiology, coagulopathy, risk of VTE, and prevention and treatment of VTE in patients with COVID‐19. These topics are reviewed in detail, along with practical issues of anticoagulant selection and duration. Although a number of international organizations have produced guideline or consensus statements, they do not all cover the same issues regarding anticoagulant therapy for patients with COVID‐19, and they do not all agree. These statements and the most recent literature are combined into a list of clinical considerations that clinicians can use for the prevention and treatment of VTE in patients with COVID‐19.


id: cord-327370-zo0n8wf6
author: Vadukul, Prakash
date: 2020-09-13
txt: ./txt/cord-327370-zo0n8wf6.txt
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url: https://doi.org/10.1136/bcr-2020-238168
doi: 10.1136/bcr-2020-238168
summary:
  We present the case of a patient with an initial presentation of COVID-19 pneumonitis requiring mechanical ventilation for nearly 2 weeks and total admission time of 3 weeks. 1 This case examines aspects of COVID-19 emphasising the increased thrombogenicity seen during infection and the potential need for extended anticoagulation following recovery particularly in those patients with severe illness and pre-existing risk factors. 18 Initial data suggest that patients with complicated COVID-19 infection have nearly three times the concentration of IL-6 compared with those exhibiting less severe disease. 24 The International Society for Thrombosis and Haemostasis suggests that prophylactic treatment with LMWH is prudent in all patients with COVID-19, particularly with severe disease or Findings that shed new light on the possible pathogenesis of a disease or an adverse effect extreme derangements in clotting parameters. 2 Compared with other populations, patients with COVID-19 appear to have higher incidences of VTE particularly with deranged clotting markers, critical care admission or reduced mobility.

title:
  Massive pulmonary embolism following recovery from COVID-19 infection: inflammation, thrombosis and the role of extended thromboprophylaxis

abstract:
  COVID-19 is the infectious disease caused by a recently discovered SARS-CoV-2. Following an initial outbreak in December 2019 in Wuhan, China, the virus has spread globally culminating in the WHO declaring a pandemic on 11 March 2020. We present the case of a patient with an initial presentation of COVID-19 pneumonitis requiring mechanical ventilation for nearly 2 weeks and total admission time of 3 weeks. She was given prophylactic dose anticoagulation according to hospital protocol during this time. Following a week at home, she was readmitted with acute massive pulmonary embolism with severe respiratory and cardiac failure, representing the first such case in the literature.


id: cord-328220-toeq4xq0
author: Smith, Kelly
date: 2020-07-06
txt: ./txt/cord-328220-toeq4xq0.txt
cache: ./cache/cord-328220-toeq4xq0.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/ajhp/zxaa245
doi: 10.1093/ajhp/zxaa245
summary:
  Areas of management requiring clinical equipoise include agent selection and dosing, continuation vs interruption of home oral anticoagulant therapy during hospital admission, and postdischarge VTE prophylaxis. CONCLUSION: Practical guidance on anticoagulation considerations and dosing suggestions are provided to assist clinicians faced with challenging anticoagulation-related situations in caring for hospitalized COVID patients until formal evidence-based guidelines become available. [8] [9] [10] [11] [12] Areas of current clinical uncertainty include dose and agent of choice, continuation vs interruption of home oral anticoagulant therapy while admitted, and postdischarge VTE prophylaxis. Upon review of the available evidence, we believe that clinicians may wish to consider a 3-tiered approach to stratifying anticoagulation intensity ( Figure 1 ), with consideration of the aforementioned factors to guide and assist in decision making. A patient may be categorized into tier II based on acuity and/or VTE risk factors (eg, a patient who is on a general medical floor but clinically deteriorating, with an upward trend in inflammatory marker and/or D-dimer levels).

title:
  Practical Considerations in Prevention and Treatment of Venous Thromboembolism in Hospitalized Patients with COVID-19

abstract:
  PURPOSE: There are increasing reports in the literature of high rates of coagulopathy and venous thromboembolism (VTE) among hospitalized patients with coronavirus disease 2019 (COVID-19). Understanding of these abnormalities is continually evolving, but these conditions may pose a risk to COVID-19 patients beyond the risk typically seen in critically ill patients. SUMMARY: There are currently no widely accepted evidence-based guidelines regarding specifics related to treatment and prevention of COVID-19–related coagulopathies. Areas of management requiring clinical equipoise include agent selection and dosing, continuation vs interruption of home oral anticoagulant therapy during hospital admission, and postdischarge VTE prophylaxis. Clinicians may wish to consider use of a stratified, 3-tiered approach of low-intensity anticoagulation, intermediate-intensity anticoagulation, and therapeutic-dose anticoagulation. Patients can be categorized by tier depending on their risk factors for VTE, acuity of illness, and laboratory values such as D-dimer level. CONCLUSION: Practical guidance on anticoagulation considerations and dosing suggestions are provided to assist clinicians faced with challenging anticoagulation-related situations in caring for hospitalized COVID patients until formal evidence-based guidelines become available.


id: cord-335020-at43c8q7
author: Porfidia, Angelo
date: 2020-05-04
txt: ./txt/cord-335020-at43c8q7.txt
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url: https://doi.org/10.1007/s11239-020-02125-4
doi: 10.1007/s11239-020-02125-4
abstract: nan
summary:
  In this article, we discuss the many doubts currently existing on the use of heparins and the correct prevention and diagnosis of VTE in COVID-19 patients, with physicians that juggle between pragmatic choices, different suggestions being released on a daily by hospital and medical societies, and the lack of solid evidence or guidelines. To support this concept, it is worth mentioning the report published by Danzi and coll., which describes the case of a 75-year-old woman who was hospitalized in Cremona, Italy, after 10 days of fever and a recent onset of dyspnea at home and was diagnosed with severe COVID-19-positive bilateral pneumonia and concomitant acute PE two days after hospital admission [19] . This issue is critical and has been taken into consideration in a recent position paper from the Italian Society on Thrombosis and Haemostasis (SISET), in which it is suggested to maintain thromboprophylaxis at home for 7-14 days after hospital discharge or in the pre-hospital phase, at least in subjects with pre-existing or persisting VTE risk factors [16] .

title:
  Venous thromboembolism and heparin use in COVID-19 patients: juggling between pragmatic choices, suggestions of medical societies


id: cord-336000-v88bq4bx
author: Barco, Stefano
date: 2020-09-09
txt: ./txt/cord-336000-v88bq4bx.txt
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mime: text/plain
url: https://doi.org/10.1186/s13063-020-04678-4
doi: 10.1186/s13063-020-04678-4
summary:
  OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. The OVID study will show whether prophylactic-dose enoxaparin improves survival and reduces any hospitalizations in ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. <30% of the expected number of patients six months after the enrolment of the first patient, also based on the course of SARS-CoV2 infections in Switzerland;  when the safety of the participants is doubtful or at risk, respectively, based on recommendations received from DSMB committee;  changes in accepted clinical practice that make the continuation of a clinical trial unwise, including the results of similar studies or the publication of international guidances.

title:
  Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial

abstract:
  OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study’s background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 10(9) cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. Secondary outcomes: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1−β = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


id: cord-339695-3ij5pjjy
title: Risk of venous thromboembolism in patients with COVID‐19: A systematic review and meta‐analysis
author: Nopp, Stephan
date: 2020-09-25
txt: ./txt/cord-339695-3ij5pjjy.txt
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extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33043231/
doi: 10.1002/rth2.12439
summary:
  [1] [2] [3] Early studies already reported on coagulation abnormalities and coagulopathy with a rather prothrombotic phenotype in patients with 5] With the better understanding of COVID-19 and its clinical course, venous thromboembolism (VTE), a disease entity covering pulmonary embolism (PE) and deep vein thrombosis (DVT), has been recognized as a particular complication of the disease. These included methodological specifics of the studies (study design, health care setting), clinical information of the study population (demographics, comorbidities, disease severity, use of pharmacological thromboprophylaxis, ultrasound screening, and D-dimer levels), and outcome specifics (definition, type, and rate of VTE). After excluding studies with a high risk of underlying bias, quantitative results from 66 studies were aggregated within a meta-analysis, including 28,173 patients (1, Figure 2 shows a Forrest plot of VTE rates, together with information on health care setting, the performance of screening and outcome definition of respective studies.

abstract:
  BACKGROUND: Venous thromboembolism (VTE) is frequently observed in patients with coronavirus disease 2019 (COVID‐19). However, reported VTE‐rates differ substantially. OBJECTIVES: We aimed at evaluating available data and estimating the prevalence of VTE in COVID‐19 patients. METHODS: We conducted a systematic literature search (MEDLINE, EMBASE, WHO COVID‐19 database) to identify studies reporting VTE‐rates in COVID‐19 patients. Studies with suspected high risk of bias were excluded from quantitative synthesis. Pooled outcome rates were obtained within a random effects meta‐analysis. Subgroup analyses were performed for different settings (intensive care unit (ICU) vs. non‐ICU hospitalization and screening vs. no screening) and the association of D‐dimer levels and VTE‐risk was explored. RESULTS: Eighty‐six studies (33,970 patients) were identified and 66 (28,173 patients, mean age: 62.6 years, 60% men, 20% ICU‐patients) were included in quantitative analysis. The overall VTE‐prevalence estimate was 14.1% (95%CI 11.6‐16.9), 40.3% (95%CI 27.0‐54.3) with ultrasound‐screening and 9.5% (95%CI 7.5‐11.7) without screening. Subgroup analysis revealed high heterogeneity, with a VTE‐prevalence of 7.9% (95%CI 5.1‐11.2) in non‐ICU and 22.7% (95%CI 18.1‐27.6) in ICU patients. Prevalence of pulmonary embolism (PE) in non‐ICU and ICU patients was 3.5% (95%CI 2.2‐5.1) and 13.7% (95%CI 10.0‐17.9). Patients developing VTE had higher D‐dimer levels (weighted mean difference 3.26 µg/ml (95%CI 2.76‐3.77) than non‐VTE patients. CONCLUSION: VTE occurs in 22.7% of patients with COVID‐19 in the ICU, but VTE risk is also increased in non‐ICU hospitalized patients. Patients developing VTE had higher D‐dimer levels. Studies evaluating thromboprophylaxis strategies in patients with COVID‐19 are needed to improve prevention of VTE.


id: cord-342603-k0f33p3l
author: Spyropoulos, Alex C.
date: 2020-05-27
txt: ./txt/cord-342603-k0f33p3l.txt
cache: ./cache/cord-342603-k0f33p3l.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32459046/
doi: 10.1111/jth.14929
summary:
  Hospitalized acutely-ill medical patients, including those with infections such as viral pneumonia, are at increased risk for VTE, and antithrombotic practice guidelines recommend thromboprophylaxis with twice-or thrice-daily subcutaneous unfractionated heparin (UFH) oncedaily subcutaneous low-molecular-weight heparin (LMWH), or fondaparinux to reduce this risk, although fondaparinux is infrequently used due to its long half-life and reversibility concerns [11, 12] . All rights reserved the absence of COVID-19-specific data, it is reasonable to consider extended-duration thromboprophylaxis with LMWH or a DOAC for at least 2 weeks and up to 6 weeks post-hospital discharge in selected COVID-19 patients who are at low risk for bleeding and with key VTE risk factors such as advanced age, stay in the ICU, cancer, a prior history of VTE, thrombophilia, severe immobility, an elevated D-dimer (>2 times ULN), and an IMPROVE VTE score of 4 or more.

title:
  Scientific and Standardization Committee Communication: Clinical Guidance on the Diagnosis, Prevention and Treatment of Venous Thromboembolism in Hospitalized Patients with COVID‐19

abstract:
  The novel coronavirus disease of 2019 (COVID‐19) pandemic, as declared by the World Health Organization, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2). Cardiovascular disease and, in particular, venous thromboembolism (VTE) has emerged as an important consideration in the management of hospitalized patients with COVID‐19. The diagnosis of VTE using standardized objective testing is problematic in these patients, given the risk of infecting non‐COVID‐19 hospitalized patients and hospital personnel, coupled with the usual challenges of performing diagnostic testing in critically‐ill patients. Early reports suggest a high incidence of VTE in hospitalized COVID‐19 patients, particularly those with severe illness, that is similar to the high VTE rates observed in patients with other viral pneumonias, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS‐CoV).


id: cord-346135-uidvtpjw
author: Parks, Anna L.
date: 2020-09-16
txt: ./txt/cord-346135-uidvtpjw.txt
cache: ./cache/cord-346135-uidvtpjw.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1016/j.thromres.2020.09.018
doi: 10.1016/j.thromres.2020.09.018
summary:
  We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. Among the protocols that J o u r n a l P r e -p r o o f Journal Pre-proof addressed a clinical question, we then reported the proportion of institutions that supported a specific practice ("consensus"). Although there was near-universal agreement on the need for heparin-based VTE prophylaxis for COVID-19 inpatients without contraindications, recommended dosing strategies varied across institutions (Figure 1a) . In contrast, four protocols (19%) specifically recommended against empiric therapeutic dosing of anticoagulation based on lab values in the absence of other clinical indications such as proven VTE.

title:
  COVID-19 coagulopathy and thrombosis: Analysis of hospital protocols in response to the rapidly evolving pandemic

abstract:
  As the Coronavirus disease 2019 (COVID-19) pandemic spread to the US, so too did descriptions of an associated coagulopathy and thrombotic complications. Hospitals created institutional protocols for inpatient management of COVID-19 coagulopathy and thrombosis in response to this developing data. We collected and analyzed protocols from 21 US academic medical centers developed between January and May 2020. We found greatest consensus on recommendations for heparin-based pharmacologic venous thromboembolism (VTE) prophylaxis in COVID-19 patients without contraindications. Protocols differed regarding incorporation of D-dimer tests, dosing of VTE prophylaxis, indications for post-discharge pharmacologic VTE prophylaxis, how to evaluate for VTE, and the use of empiric therapeutic anticoagulation. These findings support ongoing efforts to establish international, evidence-based guidelines.


id: cord-351101-l8b2cv4z
author: Uppuluri, Ellen M
date: 2020-08-11
txt: ./txt/cord-351101-l8b2cv4z.txt
cache: ./cache/cord-351101-l8b2cv4z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32780839/
doi: 10.1093/ajhp/zxaa286
summary:
  SUMMARY: Here we report development of a pulmonary embolism (PE) in a young patient without other VTE risk factors who was treated for COVID-19 in an emergency department (ED) and discharged home without VTE prophylaxis, which was consistent with current recommendations. 2, [5] [6] [7] In this article we report a case of pulmonary embolism (PE) in an ambulatory patient that developed 2 weeks after discharge from an emergency department (ED) following diagnosis of COVID-19 and treatment without DVT prophylaxis. Results were normal except for a slightly low serum sodium concentration (133 mEq/L), chloride Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis concentration (96 mmol/L), and absolute lymphocyte count (12,000/µL). [15] [16] [17] The results from these studies do not support the routine use of extended postdischarge thromboprophylaxis, and current guidelines do not recommend extended-duration outpatient VTE prophylaxis in acutely ill hospitalized medical patients, critically ill medical patients, or medical outpatients with minor risk factors for VTE, such as infection.

title:
  Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis

abstract:
  PURPOSE: Coronavirus disease 2019 (COVID-19) has been associated with thrombotic complications such as stroke and venous thromboembolism (VTE), and VTE prophylaxis for hospitalized patients with COVID-19 is recommended. However, extended postdischarge VTE prophylaxis and VTE prophylaxis for nonhospitalized patients with COVID-19 are not routinely recommended due to uncertain benefit in these populations. SUMMARY: Here we report development of a pulmonary embolism (PE) in a young patient without other VTE risk factors who was treated for COVID-19 in an emergency department (ED) and discharged home without VTE prophylaxis, which was consistent with current recommendations. The patient presented to the ED 12 days later with complaints of chest pain for 1 day and was found to have a PE within the segmental and subsegmental branches of the left lower lobe. CONCLUSION: This case suggests that nonhospitalized patients with COVID-19 may be at higher risk for VTE than patients with other medical illnesses and warrants further research into the risk of VTE in outpatients with COVID-19.


id: cord-352793-50ym7h4t
title: Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia
author: Cui, Songping
date: 2020-05-06
txt: ./txt/cord-352793-50ym7h4t.txt
cache: ./cache/cord-352793-50ym7h4t.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1111/jth.14830
doi: 10.1111/jth.14830
summary:
  Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned. METHODS: In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled. A number of studies have shown that coagulation dysfunction exists in patients with severe novel coronavirus pneumonia (NCP), [1] [2] [3] [4] which is clearly correlated with poor prognosis. Table 3 shows the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of different D-dimer levels in predicting VTE in patients with severe NCP. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

abstract:
  BACKGROUND: Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world. Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned. OBJECTIVES: To determine the incidence of VTE in patients with severe NCP. METHODS: In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled. The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed. RESULTS: The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died. The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc. If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%. CONCLUSIONS: The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis. The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.


id: cord-353692-2zotqreu
author: Dong, Fen
date: 2020-05-07
txt: ./txt/cord-353692-2zotqreu.txt
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mime: text/plain
url: https://doi.org/10.1016/j.ahj.2020.04.020
doi: 10.1016/j.ahj.2020.04.020
summary:
  title: Effect on Thromboprophylaxis among Hospitalized Patients Using a System-wide Multifaceted Quality Improvement Intervention: Rationale and Design for a Multicenter Cluster Randomized Clinical Trial in China Methods To facilitate implementation of guideline recommendations, we conduct a multicenter, adjudicator-blinded, cluster-randomized clinical trial, aiming to assess the effectiveness of a system-wide multifaceted quality improvement (QI) strategy on VTE prophylaxis improvement and thromboembolism reduction in clinical setting. In intervention group, hospitals receive the concept of appropriate in-hospital thromboprophylaxis plus a multifaceted QI which encompasses four components: (1) an electronic alert combining computer-based clinical decision support system and electronic reminders, (2) appropriate prophylaxis based on dynamic VTE and bleeding risk assessments, (3) periodical audit and interactive feedback on performance, (4) strengthened training and patient education. To better understand usual care in control group in this study, we will conduct a baseline survey in recruited hospitals before cluster randomization, collecting information on VTE and bleeding risk assessment, prophylactic approaches, initiating time for prophylaxis, etc.

title:
  Effect on Thromboprophylaxis among Hospitalized Patients Using a System-wide Multifaceted Quality Improvement Intervention: Rationale and Design for a Multicenter Cluster Randomized Clinical Trial in China

abstract:
  ABSTRACT Background Venous thromboembolism (VTE) is a life-threatening disease that can affect each hospitalized patient. But the current in-hospital thromboprophylaxis remains suboptimal and there exists a large gap between clinical practice and guideline-recommended care in China. Methods To facilitate implementation of guideline recommendations, we conduct a multicenter, adjudicator-blinded, cluster-randomized clinical trial, aiming to assess the effectiveness of a system-wide multifaceted quality improvement (QI) strategy on VTE prophylaxis improvement and thromboembolism reduction in clinical setting. Hospitals are randomized into intervention or control group. In intervention group, hospitals receive the concept of appropriate in-hospital thromboprophylaxis plus a multifaceted QI which encompasses four components: (1) an electronic alert combining computer-based clinical decision support system and electronic reminders, (2) appropriate prophylaxis based on dynamic VTE and bleeding risk assessments, (3) periodical audit and interactive feedback on performance, (4) strengthened training and patient education. In control, hospitals receive the concept of recommended prophylaxis alone without QI. Thromboprophylaxis will be at the discretion of hospitals and conducted as usual. With a final sample size of 5760 hospitalized patients in 32 hospitals on mainland China, this trial will examine the effect of QI on improvement in thromboprophylaxis and patient-centered outcomes. This is an open-label trial that patients and healthcare professionals will know group allocation after enrollment, but endpoint adjudicators and statisticians will be blinded. RCT# NCT04211181 Conclusions The system-wide multifaceted QI intervention is expected to facilitate implementation of recommended VTE prophylaxis in hospital, thereafter reducing VTE incidence and relevant adverse events among hospitalized patients in China.


