scholarly journals SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy

2021 ◽  
Author(s):  
Jae Kyu Ryu ◽  
Elif G. Sozmen ◽  
Karuna Dixit ◽  
Mauricio Montano ◽  
Yusuke Matsui ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Pulmonary Embolism ◽  
Acute Infection ◽  
Coagulation Factor ◽  
Spike Protein ◽  
Central Feature ◽  
Lung Pathology ◽  
Dependent Lung ◽  
Blood Clots ◽  
Proinflammatory Activity

Blood clots are a central feature of coronavirus disease-2019 (COVID-19) and can culminate in pulmonary embolism, stroke, and sudden death. However, it is not known how abnormal blood clots form in COVID-19 or why they occur even in asymptomatic and convalescent patients. Here we report that the Spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the blood coagulation factor fibrinogen and induces structurally abnormal blood clots with heightened proinflammatory activity. SARS-CoV-2 Spike virions enhanced fibrin-mediated microglia activation and induced fibrinogen-dependent lung pathology. COVID-19 patients had fibrin autoantibodies that persisted long after acute infection. Monoclonal antibody 5B8, targeting the cryptic inflammatory fibrin epitope, inhibited thromboinflammation. Our results reveal a procoagulant role for the SARS-CoV-2 Spike and propose fibrin-targeting interventions as a treatment for thromboinflammation in COVID-19.

Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting

The Lancet ◽  
2006 ◽  
Vol 367 (9516) ◽  
pp. 1075-1079 ◽  
Author(s):  
Liam Smeeth ◽  
Claire Cook ◽  
Sara Thomas ◽  
Andrew J Hall ◽  
Richard Hubbard ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Acute Infection ◽  
Community Setting ◽  
Vein Thrombosis ◽  
Deep Vein

scholarly journals Astragalin Inhibits Pulmonary Inflammation in Cigarette Smoking-Induced Embolism

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1526-1526
Author(s):  
Yun-Ho Kim ◽  
Young-Hee Kang
Keyword(s):  
Pulmonary Embolism ◽  
Cigarette Smoking ◽  
Pulmonary Inflammation ◽  
A549 Cells ◽  
Coagulation Factor ◽  
Alveolar Epithelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Alveolar Cells ◽  
Alveolar Epithelial

Abstract Objectives Thrombin generation is crucial to the regulation of hemostasis and thrombosis and is essential to the pathogenesis of cardiovascular disease and venous thrombosis. Pulmonary embolism is a blockage in one of the pulmonary arteries in your lung caused by blood clots due to risk factors including tobacco use. Astragalin (kaempferol 3-O-glucoside) is a flavonoid present in persimmon leaves and green tea seeds and exhibits diverse activities such as asthma and obstructive pulmonary disease. This study investigated that astragalin encumbered pulmonary inflammation caused by cigarette smoking-induced embolism. Methods Pulmonary embolism was evoked through exposure of BALB/c mice to cigarette smoke for 30 min, five days a week for eight weeks. Mice were orally administrated with 10 or 20 mg/kg astragalin for 8 weeks. For the in vitro studies, 10 U/ml thrombin was loaded to alveolar epithelial A549 cells in the absence and presence of 1–20 μM astragalin. Results Oral supplementation of astragalin reduced tissue factor and urokinase-type plasminogen activator elevated in cigarette smoking-exposed lungs. In addition, 1–20 μM astragalin attenuated the induction of protease activated receptor-1 known as coagulation factor II (thrombin) receptor-like-1, in 10 U/ml thrombin-loaded alveolar epithelial cells. Astragalin curtailed induction of the inflammatory mediators of cyclooxygenase-2, intercellular adhesion molecule-1 and inducible nitric oxide synthase in alveolar cells subjected to thrombin. Furthermore, astragalin inhibited inflammatory signaling entailing MAPK/ERK pathway. Conclusions Astragalin may be a potential agent alleviating pulmonary inflammation induced by cigarette smoking-induced embolism. Funding Sources This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A3A01094891).

Effect of selective embolization of various sized pulmonary arteries in dogs

1963 ◽  
Vol 204 (4) ◽  
pp. 619-625 ◽  
Author(s):  
John W. Hyland ◽  
George T. Smith ◽  
Lockhart B. McGuire ◽  
Donald C. Harrison ◽  
Florence W. Haynes ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Internal Diameter ◽  
Polystyrene Spheres ◽  
Selective Embolization ◽  
Blood Clots ◽  
Pulmonary Arterial ◽  
The Right

Pulmonary embolism was produced in 30 closed-chest 8-kg dogs with polystyrene spheres, glass beads, or blood clots of precise graded size. The sizes matched selectively the internal diameter of pulmonary arteries from lobar branches (5–6 mm) down to atrial arteries (0.17 mm). Emboli were injected into the right atrium until the pressure in the pulmonary artery rose 5–10 mm Hg. The number of emboli of a given size required to produce this incipient pulmonary hypertension was compared with the number of vessels of that same size as determined from the literature as well as by postmortem injection with Schlesinger mass. The number of emboli bore a constant relation to the number of vessels of that same size. With each size, the majority of vessels had to be occluded before pulmonary hypertension appeared. This was true even in the absence of anesthesia. The results support the thesis that mechanical blockade rather than vasoconstriction is the mechanism by which pulmonary hypertension is produced by emboli occluding pulmonary arterial (as opposed to arteriolar) vessels.

Use of a New Monoclonal Antibody-Based Enzyme Immunoassay for Soluble Fibrin to Exclude Pulmonary Embolism

2000 ◽  
Vol 84 (09) ◽  
pp. 474-477 ◽  
Author(s):  
Bernd-Jan Sanson ◽  
Wouter de Monyé ◽  
Jeroen Lijmer ◽  
Menno Huisman ◽  
Harry Büller ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Pulmonary Embolism ◽  
Diagnostic Accuracy ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Diagnostic Performance ◽  
Area Under The Curve ◽  
Study Cohort ◽  
Suspected Pulmonary Embolism ◽  
Soluble Fibrin

SummaryWe prospectively evaluated the diagnostic performance of a new soluble fibrin assay in 303 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off levels at which this disease can be safely excluded. In addition, the diagnostic accuracy was calculated in the subgroups of in- and outpatients. The ROC curve of the assay in the total study cohort had an area under the curve of 0.69. The cut-off level associated with a sensitivity and negative predictive value of 100% was 20 ng/ml, but the specificity was only 4%. The cut-off level with a sensitivity of 90% was 30 ng/ml, which corresponded with a specificity and negative predictive value of 27% and 86%, respectively. The diagnostic performance was comparable in the subgroups of in- and outpatients. We conclude that the soluble fibrin assay has a low diagnostic accuracy and seems unsuitable as a screening test for the exclusion of pulmonary embolism.

scholarly journals Hematology of Experimental Acute Sarcocystis bovicanis Infection in Calves. II. Serum Biochemistry and Hemostasis Studies

1981 ◽  
Vol 18 (3) ◽  
pp. 358-367 ◽  
Author(s):  
K. W. Prasse ◽  
R. Fayer
Keyword(s):  
Acute Infection ◽  
Lactic Dehydrogenase ◽  
Serum Biochemistry ◽  
Factor Vii ◽  
Thrombin Time ◽  
Holstein Friesian ◽  
Blood Smears ◽  
Blood Clots ◽  
And Control ◽  
Potassium Magnesium

Of four Holstein-Friesian calves infected with 200,000 sporocysts of Sarcocystis bovicanis, three become ill and died on days 35, 55, and 59 of a 63-day experiment. No control calves became ill or died. Serum biochemicals and hematologic indicators of hemostasis from both groups were measured throughout the experiment. Creatine phosphokinase values for both groups increased markedly during acute infection. Lactic dehydrogenase and aspartate aminotransferase values were high in infected calves on days 25 to 35 and days 24 to 63, respectively, indicating injury of muscle, liver, or other tissues. Sorbitol dehydrogenase values were significantly higher for infected than for control calves on days 25 and 35, indicating liver injury. Serum bilirubin and blood urea nitrogen values were significantly increased in three anemic infected calves from day 25 or 26 to day 35, probably reflecting destruction of erythrocytes. The fourth infected calf was not anemic and had no hyperbilirubinemia and only minimal azotemia. Serum protein and albumin values decreased in infected calves on days 21 to 30 or 35, when, although hypoalbuminemia persisted, total protein concentration increased. Glucose, calcium, sodium, and chloride values decreased in infected calves slightly before onset of illness and remained low throughout the experiment. Potassium, magnesium, and phosphorus values did not differ between infected and control calves. Activated partial thromboplastin time and Russell's viper venom time were normal; prothrombin time was significantly higher from day 27 to day 49 in infected calves. This pattern was interpreted as evidence for acquired factor VII deficiency. Abnormal retraction of blood clots and enlarged platelets in blood smears, which indicate platelet dysfunction and increased platelet turnover, respectively, were seen on days 27 through 35 in anemic infected calves. Values for thrombin time (three calves) and fibrin degradation product concentration (one calf) increased just before death of the infected calves.

Assessment of coagulation factor activation during cardiopulmonary bypass with a new monoclonal antibody

1994 ◽  
Vol 8 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Didier Journois ◽  
Philippe Mauriat ◽  
Philippe Pouard ◽  
Patrick Marchot ◽  
Jean Arniral ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cardiopulmonary Bypass ◽  
Coagulation Factor
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