Non-Sponsored Content
HEPATITIS C VIRUS
Risk of thrombosis with SARS-CoV-2 infection
Medical writer: Kirsty LEE | Last updated: 27th August 2020 | In: Cardiovascular, COVID-19, Critical Care Medicine, Infectious Disease, Internal Medicine, SARS-CoV2
Article Keywords
2019-nCoV, ARDS, COVID-19, D-Dimer, ELVO, fibrinogen, hypoxia, immunothrombosis, ischaemic stroke, neutrophils, pneumonia, RT-PCR, thrombosis
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/2019-nCoV) in late 2019 has led to a global pandemic.1Hajra A et al. Drugs. doi: 10.1007/s40265-020-01377-x Infection with SARS-CoV-2 causes coronavirus disease 2019 (COVID-19), which presents most severely with interstitial pneumonia that progresses to acute respiratory distress syndrome (ARDS) and multi-organ failure.1Hajra A et al. Drugs. doi: 10.1007/s40265-020-01377-x Non-pulmonary organ damage has emerged as a predictor of mortality.2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 However, the underlying mechanisms of COVID-19 tissue injury are currently not sufficiently understood. Current evidence indicates a prothrombotic state in COVID-19 patients that could contribute to an increased mortality rate.1,2Hajra A et al. Drugs. doi: 10.1007/s40265-020-01377-x.
Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488. Immunothrombosis is a process that under certain inflammatory conditions, is the cumulative impact of neutrophils, platelets, and the coagulation cascade to contain invading pathogens, that can aggravate tissue damage by triggering vessel occlusion and hypoxia.2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
Clinical, biochemical, and molecular evidence of this prothrombotic state and immunothrombotic dysregulation in COVID-19 has been reported, with increased frequency of pulmonary embolism, evidence of platelet-fibrin thrombi in lung tissues, and increased fibrinogen and D-Dimer levels.3Carfora V et al. J Thromb Thrombolysis. doi: 10.1007/s11239-020-02242-0 Recent trials and observational case series have highlighted that COVID-19 positive patients are at an increased risk for thrombotic events.2,4Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488.
Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397
A recent cohort study performed a histopathological assessment of autopsy cases and a myriad of other assays and tests to demonstrate immunothrombotic dysregulation as a key marker of disease severity in COVID-19.2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 The study included 62 patients in 4 cohorts – the control (n=19), COVID-19 ward patients (n=20), COVID-19 intensive care unit (ICU) patients (n=18), and non-COVID-19 pneumonia patients (n=5).2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 Patients in the COVID-19 cohorts were confirmed cases from reverse transcriptase-polymerase chain reaction (RT-PCR).2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 Reasons for exclusion from the study included severe pre-existing kidney or liver dysfunction, severe autoimmune diseases, immunosuppression, chronic infection, patients requiring extracorporeal membrane oxygenation (ECMO) therapy, and patients receiving antiplatelet medication.2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
Histopathological staining of specimens from a deceased patient with RT-PCR-confirmed SARS-CoV-2 infection revealed microvascular clots in the lung that contained platelets, fibrin, and large numbers of granulocytes.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 Immunofluorescence was further used to confirm the presence of neutrophils in the microthrombi, which were embedded in the fibrin clot.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488This finding was confirmed in four additional COVID-19 cases.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 These neutrophil-rich depositions were also present in renal and cardiac microvessels, leading to the hypothesis of activated neutrophils and immunogenic platelets driving dysregulated immunothrombosis, and thus contributing to organ injury and a systemic thrombogenic state in COVID-19.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
Results from flow cytometric activation marker analysis and isolation and staining of peripheral blood neutrophils from COVID-19 ICU patients showed the formation of circulating platelet-neutrophil-aggregates correlated linearly with pulmonary disease severity.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 D-Dimer levels were also strongly elevated in COVID-19 patients, with a significant correlation to disease severity, indicating the constant activation of the coagulation cascade in these patients.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488 The results of this study indicate that platelets, neutrophils, and the coagulation cascade contribute to disease severity, and COVID-19 patients are at risk for increased thrombotic events due to the procoagulant state.2 Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
A retrospective, observational case series conducted in the Mount Sinai Health System Hospitals across New York City over the peak three weeks of hospitalisation and death from COVID-19 (March 21 to April 12, 2020) also found that over half of emergent large vessel occlusion (ELVO) patients during this period were COVID-19 patients.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 A diagnosis of ELVO required vascular imaging confirmation of occlusion, with concomitant acute neurological deficit.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397
Over the 21-day study period, 45 patients with ELVO were identified, with a mean age of 66, 38% women, and 38% Black. Of these patients, 24 tested positive for SARS-CoV-2.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 An exploratory analysis comparing the prevalence and demographic data of ELVO patients during the COVID-19 outbreak to the ELVO patients from the year prior (March/April 2019) found a two-fold increase in the number of ELVO patients during the COVID-19 period.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 Over 50% of ELVO patients presenting during this three-week COVID-19 peak tested positive, which was significantly higher than the 19.9% infection rate in the general New York City population.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 These patients were younger, more likely to be male, and less likely to be White.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 These findings suggest an association between COVID-19 and large-vessel ischaemic stroke.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397
The data from these two studies point to a prothrombotic state upon infection with SARS-CoV-2 that is correlated with disease severity. Patients presenting with acute ischemic stroke, particularly those without typical cardiovascular risk factors, should be tested for SARS-CoV-2 infection during the pandemic.4Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397 Clinicians treating COVID-19 patients should consider prophylactic anticoagulants and vigilant monitoring for thrombotic complications.2Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
Reference
- Hajra A et al. Drugs. doi: 10.1007/s40265-020-01377-x
- Nicolai L et al. Circulation. doi: 10.1161/CIRCULATIONAHA.120.048488
- Carfora V et al. J Thromb Thrombolysis. doi: 10.1007/s11239-020-02242-0
- Majidi Shahram et al. Stroke. doi: 10.1161/STROKEAHA.120.030397
Disclaimer
This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
© Copyright 2020 MediPaper Medical Communications Ltd. – Risk of thrombosis with SARS-CoV-2 infection
YOU MAY ALSO LIKE
© Copyright 2020 MediPaper Medical Communications Ltd. – Risk of thrombosis with SARS-CoV-2 infection
The evolving role of NK1 in CINV management
Lung Cancer Update April 2021
Abemaciclib: A review of the evidence through clinical cases
The Role of Patient Blood Management for Inflammatory Bowel Disease
Breast cancer update January 2021
Osimertinib approved as the first adjuvant treatment for early non-small cell lung cancer
Increasing dose frequency of lanreotide autogel injections in neuroendocrine tumours
Cabotegravir and rilpivirine intramuscular combination safe in women
HCV-infected kidneys safe for transplantation with antiviral treatment
Baloxavir marboxil recommended as post-exposure prophylaxis to influenza by EMA
US FDA approved immune-checkpoint inhibitors updated 08-Dec-2020
Detecting metastases with PSMA-PET in prostate cancer
ASCO Guidelines for the Use of Systemic Therapies in Advanced Hepatocellular Cancer
Sotorasib for the treatment of KRASG12C mutated lung cancer
Capmatinib therapy for the treatment of MET-positive non-small cell lung cancer
Selpercatinib displays efficacy in RET fusion-positive non-small cell lung cancer
First liquid biopsy for NSCLC to receive FDA approval
ESMO releases the first guideline on NGS testing in cancers
Residual risk of hepatocellular carcinoma in older Hepatitis C patients even after viral clearance
Updated human papillomavirus vaccination and testing recommendations from the American Cancer Society
Lower-risk MDS patients benefit from novel drug, imetelstat
Carboplatin plus paclitaxel to be the new standard of care for anal cancer
ASCO 2020 Lung, Breast, and Liver Cancer Update
Second-line treatment of gastric cancer or cancer of the gastroesophegeal junction: a case study of ramucirumab in Hong Kong
Capivasertib added to fulvestrant improves progression-free survival in advanced breast cancer patients
Capivasertib plus paclitaxel improves survival of metastatic triple-negative breast cancer patients
Olaparib plus Bevacizumab as Maintenance Therapy in Ovarian Cancer
Ribociclib plus Fulvestrant Improves Survival in Advanced Breast Cancer
ASCO 2019 Lung Cancer: 36 Oral Presentations of the ASCO19 lung cancer track summarised
ASCO 2019 Breast Cancer: The ASCO19 breast cancer track summarised
Venetoclax FDA approved for CLL and SLL
FDA approves avelumab plus axitinib for renal cell carcinoma
Ramucirumab FDA approved for hepatocellular carcinoma
T-DM1 FDA approved for early breast cancer
Ivosidenib FDA-approved as first-line treatment for AML patients with IDH1 mutation
Can a novel, temporary, and fully resorbable surgical implant improve the outcome of common hockey and soccer injuries?
Pembrolizumab plus axitinib FDA approved for the first-line treatment of advanced renal cell carcinoma patients
KEYNOTE-158: pembrolizumab in previously treated advanced cervical cancer
Atezolizumab +/- cobimetinib vs regorafenib for previously treated metastatic colorectal cancer (IMblaze370)
Palbociclib approved for the treatment of male breast cancer
Erdafitinib FDA approved for the treatment of metastatic urothelial carcinoma
Atezolizumab FDA approved for extensive-stage small cell lung cancer (SCLC)
Atezolizumab FDA approved for PD-L1 positive unresectable triple-negative breast cancer
Combinations: upcoming treatment strategies in metastatic renal cell carcinoma
Trifluridine/tipiracil combination FDA approved for metastatic gastric or GEJ adenocarcinoma
Pembrolizumab FDA approved for adjuvant treatment of melanoma
Trastuzumab-biosimilar Ontruzant® FDA approved in several indications
Cabozantinib FDA approved in HCC patients failing sorafenib
Erasmus University MC investigating a new surgical matrix to reduce post-operative complications
Keytruda® FDA approved for recurrent and metastatic Merkel cell carcinoma
Calaspargase pegol-mknl (Asparlas®) FDA approved in paediatric and young adult acute lymphoblastic leukaemia (ALL) patients
Elzonris™ FDA approved for blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Olaparib (Lynparza) FDA approved as maintenance for BRCAm ovarian cancer
Trastuzumab-biosimilar Herzuma® FDA approved in HER2+ breast cancer
Frontline atezolizumab plus bevacizumab and chemotherapy FDA approved for metastatic non-squamous NSCLC
MURANO: off-drug progression-free survival after 2 years venetoclax plus 6 cycles Rituximab
TIGR®Matrix shows promising results when used for incisional hernia prevention in septic patients undergoing laparoscopy
Gilteritinib (Xospata®) FDA approved for relapsed or refractory AML harbouring FLT3 mutations
TKR inhibitor larotrectinib (Vitrakvi®) FDA approved for cancers with NTRK gene fusion
FDA Approves Truxima as Biosimilar to Rituxan
Venetoclax plus azacitidine, decitabine, or low-dose cytarabine FDA approved in elderly AML patients
Glasdegib plus low-dose cytarabine (LDAC) approved in elderly AML patients
The Emerging Role of Yttrium-90 in Primary and Metastatic Liver Cancer
Emapalumab FDA approved in adult and paediatric patients with primary hemophagocytic lymphohistiocytosis
Brentuximab vedotin (Adcetris®) plus chemotherapy approved for several CD30 expressing lymphomas
Fully resorbable synthetic matrix offers improved safety for breast cancer patients undergoing immediate breast reconstruction
Pembrolizumab FDA approved in hepatocellular carcinoma patients pretreated with sorafenib
Lorlatinib FDA approved for metastatic ALK-positive NSCLC
ESMO 2018 HCC: The ESMO18 hepatobiliary cancer track summarised
Pembrolizumab plus chemotherapy approved for metastatic squamous NSCLC
Management of Immune-Mediated Hepatitis: a Case Report
PARPi talazoparib FDA approved for deleterious gBRCAm HER2‑negative breast cancer
Anti-PD1 sintilimab plus biosimilar bevacizumab receive IND-status by China NMPA
IMpower133: first-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer
Pembrolizumab plus chemotherapy effective in squamous NSCLC
Ipilimumab plus nivolumab for persistent or recurrent ovarian cancer
Brigatinib prolongs PFS compared to crizotinib in ALK-Positive NSCLC
CAR-T axicabtagene ciloleucel granted Orphan Drug designation for B-Cell Lymphoma by the Japan MHLW
PD-1 mAB cemiplimab FDA approved for locally advanced and metastatic cutaneous squamous cell carcinoma (CSCC)
JAVELIN Lung 200: avelumab vs docetaxel for pretreated NSCLC
Dacomitinib FDA approved for the first-line treatment of metastatic EGFR-mutated NSCLC
Duvelisib FDA approved for adult patients with R/R CLL or SLL
Duvelisib FDA approved for adult patients with R/R follicular lymphoma
Frontline atezolizumab plus chemotherapy improves PFS in NSCLC
First-line osimertinib vs EGFR-TKI in Asian patients with advanced NSCLC
Early breast cancer treatment in China remains conservative
ImmunoOncology: Dr Oscar Chan on the treatment of irAE rash
Prof Stefan Kasper on I-O in EXTREME-ineligible SCCHN
Camrelizumab anti-PD-1 with or without chemotherapy for NPC
Moxetumomab pasudotox-tdfk FDA approved for hairy cell leukaemia
I-O in Special Populations: the Treatment of Immunotherapy-Induced Pneumonitis
Venetoclax FDA label updated to include Minimal Residual Disease negativity data
Quizartinib receives Orphan Drug designation for FLT3-mutated AML in Japan
Capmatinib plus gefitinib promising in MET-dysregulated NSCLC
CAR-TCR Summit 2018: Preliminary first-in-human data with CAR-Claudin18.2-T in gastric and pancreatic cancer
DRIVER connects cancer patients in China and the United States to the best care
Plasma TMB predicts response to atezolizumab in NSCLC patients
First-in-Class Oncology Vaccine BIL06v Starts Phase 1 Evaluation
Pembrolizumab and atezolizumab USPIs updated by FDA
Nivolumab FDA approved for patients with metastatic small cell lung cancer (SCLC)
Pembrolizumab plus pemetrexed-platinum FDA approved for first-line treatment of metastatic non-squamous NSCLC
Talazoparib in advanced breast cancer patients with a germline BRCA1/2 mutation
CheckMate 032: Nivolumab +/- ipilimumab for metastatic esophagogastric cancer
Lenvatinib FDA approved for 1st-line treatment of HCC
Pan-EGFR TKI pirotinib has commenced into Phase II clinical testing in China
FDA approved mogamulizumab for adult patients with relapsed or refractory CTCL
Lusutrombopag FDA approved for thrombocytopenia in adult chronic liver disease patients
Iobenguane I-131 FDA approved for rare adrenal neuroendocrine tumours
Osimertinib in patients with T790M-positive advanced non-small cell lung cancer and brain metastases (AURA3)
Anti-PD1 with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
Ivosidenib FDA approved for relapsed or refractory acute myeloid leukemia
Filgrastim-aafi FDA approved as Filgrastim Biosimilar
Ribociclib FDA label updated to include pre- and perimenopausal women
Enzalutamide FDA approved for castration-resistant prostate cancer (CRPC)
EBV, MSI, and CPS predict pembrolizumab outcome in gastric cancer
Ipilimumab plus nivolumab FDA approved for MSI-H and dMMR pre-treated mCRC
Combination encorafenib plus binimetinib for unresectable/metastatic BRAF V600E or V600K-positive melanoma FDA approved
ASCO 2018 NSCLC: The ASCO18 Lung Cancer Track Summarised
FDA limits use of atezolizumab and pembrolizumab in urothelial carcinoma
ASCO 2018 Breast Cancer: The ASCO18 breast cancer track summarised
Bevacizumab in combination with carboplatin and paclitaxel FDA approved for several types of gynaecological cancers
FDA approved pembrolizumab for 3rd-line PMBCL in adult and pediatric patients
FDA approved pembrolizumab for chemotherapy-refractory r/m cervical cancer with PD-L1 CPS ≥1
ASCO 2018 HCC: The ASCO18 hepatocellular cancer track summarised
FDA approves venetoclax in 2nd-line for patients with CLL or SLL
FDA approved biosimilar pegfilgrastim to decrease the chance of febrile neutropenia in patients with non-myeloid cancers on myelosuppressive chemotherapy
AACR 2018: first-line atezolizumab, bevacizumab plus chemotherapy active in non-squamous NSCLC
US FDA approved CAR-T cell and BiTE immunotherapy – Updated 2-May-2018
Adjuvant dabrafenib plus trametinib FDA approved for BRAF V600E or V600K melanoma
Nivolumab-Ipilimumab Combination: A New Option for TMB-High NSCLC (CheckMate 227)
FDA approved osimertinib for the 1st-line treatment of patients with EGFR exon 19 deletions or exon 21 L858R mutations positive metastatic non-small cell lung cancer (NSCLC)
Frontline Combination of Pembrolizumab and Chemotherapy: A New Standard of Care for Non-squamous NSCLC
Frontline nivolumab plus ipilimumab approved for intermediate or poor risk advanced RCC
Pembrolizumab effective in frontline NSCLC with low PD-L1 expression
Everolimus suspension approved in TSC-associated partial-onset seizures
I-O in Special Populations: Diabetes and Concomitant Steroids
Crizotinib beneficial for East-Asian NSCLC patients with ROS1 alterations
Death due to cancer on the decline for most tumours in Europe
Nivolumab for NPC: immunotherapy active in nasopharyngeal carcinoma (NCI-9742)
FDA granted accelerated approval to blinatumomab for the treatment of adult and paediatric patients with B-cell precursor ALL in first or second complete remission with MRD ≥0.1%
Making sense of 1st-line immunotherapy in non-small cell lung cancer (NSCLC)
Achieving Long-Term Survival in the First-Line Treatment of Metastatic Renal Cell Carcinoma; A Balancing Act of Efficacy and Side-Effects
Do you know your lifetime risk on Pancreatic Cancer?
Luminal Breast Cancer: can CDK4/6 Inhibition by Palbociclib Improve on Chemotherapy?
Pembrolizumab approved for advanced gastric cancer
Nivolumab approved for sorafenib-refractory HCC
Nivolumab for Renal Carcinoma: Getting the Most Out of PD-1 Immunotherapy
Should all Women with Endocrine-Sensitive and Operable Breast Cancer Receive Adjuvant Hormonal Therapy?
Interested in Attending an Immunooncology Conference?
ESMO16 Breast Cancer: Palbociclib, Ribociclib and Abemaciclib Data
PD-L1 Biomarker: a Comparison of ASCO2016 PD-1 and PD-L1 Data
Novel Biomarker for Ipilimumab Treatment may aid Future Patient Selection in Several Malignancies
ESMO16 Ipilimumab data – Download the PPT
ESMO16 Pembrolizumab data – Download the PPT
ESMO16 Durvalumab, Avelumab, Tremelimumab Data – Download the PPT
ESMO16 Atezolizumab data – Download the PPT
ESMO16 Nivolumab data – Download the PPT
Cancer symptom awareness linked to survival
ASCO Guideline NeoAdjuvant Chemotherapy for Ovarian Cancer Updated
IMM101 plus Gemcitabine Hopeful in Metastatic Pancreatic Cancer
Palbociclib (Ibrance®): First in Class CDK4/6 Inhibitor
Ki67 in Breast Cancer: an overview
ASCO16 Ribociclib & Abemaciclib Data
ASCO16 palbociclib (Ibrance©) Data
ASCO16 Avelumab, Durvalumab, and Tremelimumab
ASCO16 Atezolizumab (Tecentriq©) Data
ASCO16 Ipilimumab (Yervoy©) Data
ASCO16 Nivolumab (Opdivo©) Data
ASCO16 Pembrolizumab (Keytruda©) Data