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1.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

2.
Eur J Ophthalmol ; 32(1): NP168-NP172, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1633471

ABSTRACT

INTRODUCTION: Papillophlebitis is a rare condition characterized by venous congestion and optic disc edema, which has been suggested to occur as a consequence of inflammation of the retinal veins or, possibly, the capillaries of the optic disc, leading to venous insufficiency and compression of the central retina vein. The disease affects healthy young adults and commonly has a benign course, however, if complications such as macular edema or ischemia appears, treatment should be instituted immediately to avoid poor prognosis. CASE REPORT: A 40-year old white male patient consulted for a slight decrease in the sensitivity of the visual field in his left eye (OS). Visual acuities (VA) were 20/20 in both eyes. OS fundus examination showed dilated and tortuous retinal vessels, disc edema, and retinal hemorrhages. The patient was diagnosed with papillophlebitis. OS VA decreased to 20/200 due to macular edema, and he was treated with a intravitreal dexamethasone implant. An exhaustive and interdisciplinary exploration process was performed, identifying a recent disease and recovery of Covid-19 as the only factor of inflammation and coagulation alteration. Other systemic diseases were excluded. We also describe a rapid decrease in disc and macular edema after intravitreal dexametasone injection, which could support the inflammatory hypothesis. CONCLUSION: The importance of this case lies in the possible association of papillophlebitis with the new Covid-19 disease. We believe that the inflammatory reaction and the coagulation alteration present in our patient due to Sars-Cov2 coronavirus may have acted as risk factors for the development of papillophlebitis.


Subject(s)
COVID-19 , Macular Edema , Retinal Vein Occlusion , Adult , Humans , Inflammation , Male , RNA, Viral , SARS-CoV-2
3.
Thromb Haemost ; 121(8): 1031-1042, 2021 08.
Article in English | MEDLINE | ID: covidwho-1324458

ABSTRACT

Hemostatic changes induced by extracorporeal membrane oxygenation (ECMO) support have been yet poorly documented in coronavirus-19 (COVID-19) patients who have a baseline complex hypercoagulable state. In this prospective monocentric study of patients with severe acute respiratory distress syndrome (ARDS) rescued by ECMO, we performed longitudinal measurements of coagulation and fibrinolysis markers throughout the course of ECMO support in 20 COVID-19 and 10 non-COVID-19 patients. Blood was sampled before and then 24 hours, 7, and 14 days after ECMO implantation. Clinical outcomes were prospectively assessed until discharge from the intensive care unit or death. The median age of participants was 47 (35-56) years, with a median body mass index of 30 (27-35) kg/m2, and a Sepsis-related Organ Failure Assessment score of 12 (8-16). Baseline levels of von Willebrand factor, fibrinogen, factor VIII, prothrombin F1 + 2, thrombin-antithrombin, D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were elevated in both COVID-19 and non-COVID-19 ARDS patients, indicating that endothelial activation, endogenous thrombin generation, and fibrinolysis shutdown occur in all ARDS patients before ECMO implantation. From baseline to day 7, thrombin generation (prothrombin F1 + 2, p < 0.01) and fibrin formation markers (fibrin monomers, p < 0.001) significantly increased, further resulting in significant decreases in platelet count (p < 0.0001) and fibrinogen level (p < 0.001). PAI-1 levels significantly decreased from baseline to day 7 (p < 0.0001) in all ARDS patients. These changes were more marked in COVID-19 patients, resulting in 14 nonfatal and 3 fatal bleeding. Additional studies are warranted to determine whether monitoring of thrombin generation and fibrinolysis markers might help to early predict bleeding complications in COVID-19 patients supported by ECMO.


Subject(s)
Blood Coagulation , COVID-19/therapy , Extracorporeal Membrane Oxygenation/adverse effects , Fibrinolysis , Respiratory Distress Syndrome/therapy , Adult , COVID-19/blood , COVID-19/complications , Female , Hemorrhage/etiology , Humans , Male , Middle Aged , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/complications , von Willebrand Factor/analysis
4.
Front Med (Lausanne) ; 8: 626384, 2021.
Article in English | MEDLINE | ID: covidwho-1263009

ABSTRACT

Objective: We aimed to explore the dynamic changes in coagulation function and the effect of age on coagulation function in patients with pneumonia under admission and non-admission treatment. Methods: We included 178 confirmed adult inpatients with COVID-19 from Wuhan Union Hospital Affiliated to Huazhong University of Science and Technology (Wuhan, China). Patients were classified into common types, and all were cured and discharged after hospitalization. We recorded the time of the first clinical symptoms of the patients and performed blood coagulation tests at the time of admission and after admission. In total, eight factors (TT, FIB, INR, APTT, PT, DD, ATIII, and FDP) were analyzed. Patients were classified into four groups according to the time from the first symptom onset to hospital admission for comparative analysis. The patients who were admitted within 2 weeks of disease onset were analyzed for the dynamic changes in their blood coagulation tests. Further division into two groups, one group comprising patients admitted to the hospital within 2 weeks after the onset of disease and the other comprising patients admitted to the hospital 2 weeks after disease onset, was performed to form two groups based on whether the patient ages were over or under 55 years. Chi-square tests and T tests were used to explore the dynamic changes in coagulation function and the influence of age on the results of coagulation function tests. Results: A total of 178 inpatients, 34 of whom underwent dynamic detection, were included in this analysis. We divided these patients into four groups according to the interval between the onset of COVID-19 pneumonia and the time to admission in the hospital: the 1-7 days (group 1), 8-14 days (group 2), 15-21 days (group 3), and >21-days (group 4). Eight factors all increased within 2 weeks after onset and gradually decreased to normal 2 weeks before the patient was admitted. The changes in coagulation function of patients admitted to the hospital were similar. After being admitted to the hospital, the most significant decreases among the eight factors were between week 2 and 3. There were distinct differences among the eight factors between people older than 55 years and those younger than 55 years. In the first 2 weeks after being admitted, the levels of the eight factors in patients >55 years were significantly higher than those in patients <55 years, and after another 2 weeks of treatment, the factor levels in both age groups returned to normal. Conclusion: The eight factors all increased within 2 weeks after onset and gradually decreased to normal after 2 weeks regardless of treatment. Compared with patients younger than 55 years, patients older than 55 years have greater changes in their blood coagulation test values.

5.
Thromb J ; 19(1): 35, 2021 May 31.
Article in English | MEDLINE | ID: covidwho-1249557

ABSTRACT

BACKGROUND: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. METHODS: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. RESULTS: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 µg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 µg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. CONCLUSION: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.

6.
Expert Rev Anti Infect Ther ; 19(11): 1397-1413, 2021 11.
Article in English | MEDLINE | ID: covidwho-1174805

ABSTRACT

INTRODUCTION: SARS-CoV-2, the causative agent of COVID-19, attacks the immune system causing an exaggerated and uncontrolled release of pro-inflammatory mediators (cytokine storm). Recent studies propose an active role of coagulation disorders in disease progression. This hypercoagulability has been displayed by marked increase in D-dimer in hospitalized patients. AREAS COVERED: This review summarizes the pathogenesis of SARS-CoV-2 infection, generation of cytokine storm, the interdependence between inflammation and coagulation, its consequences and the possible management options for coagulation complications like venous thromboembolism (VTE), microthrombosis, disseminated intravascular coagulation (DIC), and systemic and local coagulopathy. We searched PubMed, Scopus, and Google Scholar for relevant reports using COVID-19, cytokine storm, and coagulation as keywords. EXPERT OPINION: A prophylactic dose of 5000-7500 units of low molecular weight heparin (LMWH) has been recommended for hospitalized COVID-19 patients in order to prevent VTE. Treatment dose of LMWH, based on disease severity, is being contemplated for patients showing a marked rise in levels of D-dimer due to possible pulmonary thrombi. Additionally, targeting PAR-1, thrombin, coagulation factor Xa and the complement system may be potentially useful in reducing SARS-CoV-2 infection induced lung injury, microvascular thrombosis, VTE and related outcomes like DIC and multi-organ failure.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Cytokine Release Syndrome , Venous Thromboembolism , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/virology , COVID-19/complications , Cytokine Release Syndrome/virology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Venous Thromboembolism/drug therapy , Venous Thromboembolism/virology
7.
Mol Biol Rep ; 48(3): 2917-2928, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1173966

ABSTRACT

The renin-angiotensin-aldosterone system and its metabolites play an important role in homeostasis of body, especially the cardiovascular system. In this study, we discuss the imbalance of multiple systems during the infection and the importance of therapeutic choice, dosing, and laboratory monitoring of cardiac and anti-coagulant therapies in COVID-19 patients. The crosstalk between angiotensin, kinin-kallikrein system, as well as inflammatory and coagulation systems plays an essential role in COVID-19. Cardiac complications and coagulopathies imply the crosstalks between the mentioned systems. We believe that the blockage of bradykinin can be a good option in the management of COVID-19 and CVD in patients and that supportive treatment of respiratory and cardiologic complications is needed in COVID-19 patients. Ninety-one percent of COVID-19 patients who were admitted to hospital with a prolonged aPTT were positive for lupus anticoagulant, which increases the risk of thrombosis and prolonged aPTT. Therefore, the question that is posed at this juncture is whether it is safe to use the prophylactic dose of heparin particularly in those with elevated D-dimer levels. It should be noted that timing is of high importance in anti-coagulant therapy; therefore, we should consider the level of D-dimer, fibrinogen, drug-drug interactions, and risk factors during thromboprophylaxis administration. Fibrinogen is an independent predictor of resistance to heparin and should be considered before thromboprophylaxis. Alteplase and Futhan might be a good choice to assess the condition of heparin resistance. Finally, the treatment option, dosing, and laboratory monitoring of anticoagulant therapy are critical decisions in COVID-19 patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Thrombosis , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Bradykinin/blood , COVID-19/complications , COVID-19/immunology , COVID-19/physiopathology , COVID-19/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation/immunology , Inflammation/virology , Kallikreins/blood , Renin-Angiotensin System/immunology , Renin-Angiotensin System/physiology , Thrombosis/drug therapy , Thrombosis/prevention & control , Thrombosis/virology
8.
J Clin Med ; 10(6)2021 Mar 15.
Article in English | MEDLINE | ID: covidwho-1136512

ABSTRACT

Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated. Kidney susceptibility to SARS-CoV-2 infection is determined by the presence of angiotensin-converting enzyme 2 (ACE2) receptor which is used as port of the viral entry into targeted cells, tissue tropism, pathogenicity and subsequent viral replication. The SARS-CoV-2 cellular entry receptor, ACE2, is widely expressed in proximal epithelial cells, vascular endothelial and smooth muscle cells and podocytes, where it supports kidney integrity and function via the enzymatic production of Angiotensin 1-7 (Ang 1-7), which exerts vasodilatory, anti-inflammatory, antifibrotic and diuretic/natriuretic actions via activation of the Mas receptor axis. Loss of this activity constitutes the potential basis for the renal damage that occurs in COVID-19 patients. Indeed, several studies in a small sample of COVID-19 patients revealed relatively high incidence of acute kidney injury (AKI) among them. Although SARS-CoV-1 -induced AKI was attributed to multiorgan failure and cytokine release syndrome, as the virus was not detectable in the renal tissue of infected patients, SARS-CoV-2 antigens were detected in kidney tubules, suggesting that SARS-CoV-2 infects the human kidney directly, and eventually induces AKI characterized with high morbidity and mortality. The mechanisms underlying this phenomenon are largely unknown. However, the fact that ACE2 plays a crucial role against renal injury, the deprivation of the kidney of this advantageous enzyme, along with local viral replication, probably plays a central role. The current review focuses on the critical role of ACE2 in renal physiology, its involvement in the development of kidney injury during SARS-CoV-2 infection, renal manifestations and therapeutic options. The latter includes exogenous administration of Ang (1-7) as an appealing option, given the high incidence of AKI in this ACE2-depleted disorder, and the benefits of ACE2/Ang1-7 including vasodilation, diuresis, natriuresis, attenuation of inflammation, oxidative stress, cell proliferation, apoptosis and coagulation.

9.
Vopr Virusol ; 66(1): 40-46, 2021 03 07.
Article in Russian | MEDLINE | ID: covidwho-1120830

ABSTRACT

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , COVID-19/drug therapy , Coronary Disease/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Hypertension/drug therapy , Intracranial Arteriosclerosis/drug therapy , Acetylcysteine/therapeutic use , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Atrial Fibrillation/diagnosis , Atrial Fibrillation/mortality , Atrial Fibrillation/virology , Azithromycin/therapeutic use , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Cohort Studies , Comorbidity , Coronary Disease/diagnosis , Coronary Disease/mortality , Coronary Disease/virology , Dabigatran/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Female , Humans , Hypertension/diagnosis , Hypertension/mortality , Hypertension/virology , Indoles/therapeutic use , Interferon alpha-2/therapeutic use , Intracranial Arteriosclerosis/diagnosis , Intracranial Arteriosclerosis/mortality , Intracranial Arteriosclerosis/virology , Male , Middle Aged , Pyrazoles/therapeutic use , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Severity of Illness Index , Survival Analysis
10.
Cureus ; 13(1): e12990, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1115544

ABSTRACT

Thrombocytopenia occurs in one-third of patients with coronavirus disease 2019 (COVID-19) infection and can indicate the severity of disease and may also increase the bleeding risk of performing invasive procedures. We present a pregnant patient with COVID-19 infection with the lowest platelet count described in the literature to date. The patient presented in labor at 38 weeks gestation with no other symptoms and was found to be positive on routine COVID-19 testing. The routine complete blood count upon admission was significant for a platelet count of 6 x 109/L which was rechecked and resulted in a platelet count of 8 x 109/L. The etiology of her thrombocytopenia was not clear prior to delivery as preeclampsia with severe features and lupus exacerbation were also possibilities that were considered. However, after delivery it became apparent that COVID-19 likely had a significant impact contributing to her severe thrombocytopenia. Her care was complicated by postpartum hemorrhage resulting in massive transfusion. This case highlights the importance of evaluating platelet count and coagulation status in COVID-19 patients, even if asymptomatic.

11.
Eur Heart J Acute Cardiovasc Care ; 10(3): 310-319, 2021 May 11.
Article in English | MEDLINE | ID: covidwho-1114844

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.


Subject(s)
Cardiovascular Diseases/blood , Fibrin Fibrinogen Degradation Products/metabolism , Pandemics , Troponin/blood , Biomarkers/blood , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Comorbidity , Humans , Prognosis , Risk Factors , SARS-CoV-2
12.
Adv Exp Med Biol ; 1321: 33-43, 2021.
Article in English | MEDLINE | ID: covidwho-1114234

ABSTRACT

A number of different viral species are known to have effects on the endothelium. These include dengue, Ebola, Marburg, Lassa fever, yellow fever and influenza viruses, cytomegalovirus and coronaviruses. There are currently seven human endemic coronaviruses, all of which cause respiratory diseases and bind to receptors found within the endothelium. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) is highly infectious. Like its predecessor, SARS-CoV, it binds to angiotensin-converting enzyme-2 (ACE-2), which is expressed in many cell types, particularly in the lung, including endothelial cells. The initiation of a cytokine storm by the virus along with infection of endothelial cells leads to apoptosis and structural and functional changes that attenuate vascular integrity in many organs including the lungs, heart, liver and kidney. Endothelial damage also enhances the coagulation pathway leading to thrombus formation in major vessels and capillaries. Infection with SARS-CoV-2 has an adverse outcome for individuals with particular comorbid diseases, e.g. hypertension, obesity, type 2 diabetes and cardiovascular disease. It is possible that this is due to the presence of pre-existing endothelial dysfunction and systemic inflammation in subjects with these diseases. Therapies for COVID-19 that target the endothelium, the inflammatory response and the coagulation pathway are currently under trial.


Subject(s)
COVID-19 , Coronavirus , Diabetes Mellitus, Type 2 , Endothelial Cells , Humans , SARS-CoV-2
13.
J Intensive Care Med ; 36(6): 689-695, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1109888

ABSTRACT

BACKGROUND: D-dimer concentration has been used by institutions to identify candidates for intensified anticoagulant treatment for venous thromboembolism prevention and for the mitigation of the microthrombotic complications associated with COVID-19. Thromboelastography (TEG) maximum amplitude (MA) has been validated as a marker of hypercoagulability and MA ≥68 mm has been utilized as a marker of hypercoagulability in other conditions. METHODS: The goal of this study was to evaluate the relationship between coagulation, inflammatory, and TEG parameters in patients with COVID-19 on extracorporeal membrane oxygenation (ECMO). We performed a single-center retrospective analysis of consecutive patients that received ECMO for the treatment of COVID-19. TEG, inflammatory, and coagulation markers were compared in patients with and without a thrombotic complication. Correlation tests were performed to identify the coagulation and inflammatory markers that best predict hypercoagulability as defined by an elevated TEG MA. RESULTS: A total of 168 TEGs were available in 24 patients. C-reactive protein and fibrinogen were significantly higher in patients that developed a thrombotic event versus those that did not (P = 0.04 and P = 0.04 respectively). D-dimer was negatively correlated with TEG MA (P < 0.01), while fibrinogen was positively correlated (P < 0.01). A fibrinogen >441 mg/dL was found to have a sensitivity of 91.2% and specificity of 85.7% for the detection of MA ≥68 mm. CONCLUSIONS: In critically ill patients with COVID-19 treated with ECMO, D-dimer concentration had an inverse relationship with degree of hypercoagulability as measured by TEG MA. D-dimer elevation may potentially reflect hemostatic perturbation in patients on ECMO or the severity of COVID-19 related sepsis rather than designate patients likely to benefit from anticoagulation. Fibrinogen concentration may represent a more useful marker of hypercoagulability in this population.


Subject(s)
COVID-19/blood , Extracorporeal Membrane Oxygenation , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Thrombophilia/blood , Thrombophilia/virology , Adult , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Thrombelastography
14.
J Cardiothorac Vasc Anesth ; 35(7): 1953-1963, 2021 07.
Article in English | MEDLINE | ID: covidwho-1093370

ABSTRACT

The European Association of Cardiothoracic Anaesthesiology (EACTA) and the Society of Cardiovascular Anesthesiologists (SCA) aimed to create joint recommendations for the perioperative management of patients with suspected or proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing cardiac surgery or invasive cardiac procedures. To produce appropriate recommendations, the authors combined the evidence from the literature review, reevaluating the clinical experience of routine cardiac surgery in similar cases during the Middle East Respiratory Syndrome (MERS-CoV) outbreak and the current pandemic with suspected coronavirus disease 2019 (COVID-19) patients, and the expert opinions through broad discussions within the EACTA and SCA. The authors took into consideration the balance between established procedures and the feasibility during the present outbreak. The authors present an agreement between the European and US practices in managing patients during the COVID-19 pandemic. The recommendations take into consideration a broad spectrum of issues, with a focus on preoperative testing, safety concerns, overall approaches to general and specific aspects of preparation for anesthesia, airway management, transesophageal echocardiography, perioperative ventilation, coagulation, hemodynamic control, and postoperative care. As the COVID-19 pandemic is spreading, it will continue to present a challenge for the worldwide anesthesiology community. To allow these recommendations to be updated as long as possible, the authors provided weblinks to international public and academic sources providing timely updated data. This document should be the basis of future task forces to develop a more comprehensive consensus considering new evidence uncovered during the COVID-19 pandemic.


Subject(s)
Anesthesia, Cardiac Procedures , Anesthesiology , COVID-19 , Anesthesiologists , China , Consensus , Humans , Pandemics , SARS-CoV-2
15.
Mol Cell Biochem ; 476(6): 2421-2427, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1092035

ABSTRACT

Aggressive inflammatory response leading to hypercoagulability has been found to be associated with disease severity in COVID-19 patients and portends bad treatment outcome. A state of acute disseminated intravascular coagulation (DIC), along with pulmonary embolism and/or deep vein thrombosis, has been observed in critically ill ICU patients. Autopsy reports of COVID-19 patients demonstrated microthrombi in lungs and in other organs, as well as marked inflammatory changes, characteristic clinicopathological features that exacerbate disease severity. Vitamin D supplementation was recommended by many clinicians across the globe to improve clinical symptoms of COVID-19 patients, mainly because of its immunomodulatory roles on immune cells. Furthermore, vitamin D and its associated molecules are also known to directly or indirectly regulate various thrombotic pathways. We propose that vitamin D supplementation not only attenuates the risk of Acute Respiratory Disease Syndrome (ARDS) but it also may have a role in reducing coagulation abnormalities in critically ill COVID-19 patients. The overarching goal of this review is to discuss the effects of vitamin D on coagulation pathways and other intertwined processes leading to thrombosis. Many clinical trials are currently investigating the efficacy of vitamin D supplementation in reducing the risk of COVID-19 infection. However, randomized placebo control clinical trials are also necessary to ascertain the effect of vitamin D supplementation on reducing the risk of coagulopathy in COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/etiology , Vitamin D/pharmacology , Vitamin D/physiology , Blood Coagulation Disorders/virology , COVID-19/complications , Humans , Urachal Cyst/etiology , Vitamin D Deficiency/virology
16.
Medicine (Baltimore) ; 100(7): e24537, 2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1091184

ABSTRACT

BACKGROUND: The role of coagulation dysfunction in Severe Coronavirus Disease 2019 (COVID-19) is inconsistent. We aimed to explore the impact of coagulation dysfunction amongst patients with COVID-19. METHODS: We searched PubMed, Cochrane and Embase databases from December 1, 2019 to April 27, 2020 following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Data about coagulation (Platelets, PT, APTT, fibrin, fibrinogen degradation products, D-dimer), prevalence of coagulation dysfunction and mortality were extracted. Meta regression was used to explore the heterogeneity. RESULTS: Sixteen observational studies were included, comprising 2, 139 patients with confirmed COVID-19. More severe COVID-19 cases tended to have higher mean D-dimer (SMD 0.78, 95% CI 0.53 to 1.03, P < .001). The similar pattern occurred with PT and fibrin, with a contrary trend for PLTs. Coagulation dysfunction was more frequent in severe cases compared to less severe (SMD 0.46, 95% CI 0.25 to 0.67, P < .001). Higher mortality was associated with COVID-19-related coagulopathy (RR 10.86, 2.86 to 41.24, P < .001). Prevalence of ARDS was increased in more severe patients than less severe cases (RR 16.52, 11.27 to 24.22, P < .001). PT, fibrin and D-dimer levels elevated significantly in non-survivors during hospitalization. CONCLUSION: Presence of coagulation dysfunction might be associated with COVID-19 severity, and coagulopathy might be associated with mortality. Coagulation markers including PT, fibrin and D-dimer may imply the progression of COVID-19. This illuminates the necessity of effectively monitoring coagulation function for preventing COVID-19-related coagulopathy, especially in severe patients. For the obvious heterogeneity, the quality of the evidence is compromised. Future rigorous randomized controlled trials that assess the correlation between coagulation and COVID-19 are needed. TRIAL REGISTRATION: PROSPERO (CRD42020183514).


Subject(s)
Blood Coagulation Disorders/virology , Blood Coagulation Factors , COVID-19/complications , Biomarkers/blood , Blood Coagulation Disorders/mortality , COVID-19/mortality , Humans , SARS-CoV-2
17.
Thromb J ; 19(1): 8, 2021 Feb 10.
Article in English | MEDLINE | ID: covidwho-1079245

ABSTRACT

BACKGROUND: The progression of coagulation in COVID-19 patients with confirmed discharge status and the combination of autopsy with complete hemostasis parameters have not been well studied. OBJECTIVE: To clarify the thrombotic phenomena and hemostasis state in COVID-19 patients based on epidemiological statistics combining autopsy and statistical analysis. METHODS: Using autopsy results from 9 patients with COVID-19 pneumonia and the medical records of 407 patients, including 39 deceased patients whose discharge status was certain, time-sequential changes in 11 relevant indices within mild, severe and critical infection throughout hospitalization according to the Chinese National Health Commission (NHC) guidelines were evaluated. Statistical tools were applied to calculate the importance of 11 indices and the correlation between those indices and the severity of COVID-19. RESULTS: At the beginning of hospitalization, platelet (PLT) counts were significantly reduced in critically ill patients compared with severely or mildly ill patients. Blood glucose (GLU), prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer levels in critical patients were increased compared with mild and severe patients during the entire admission period. The International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) score was also high in critical patients. In the relatively late stage of nonsurvivors, the temporal changes in PLT count, PT, and D-dimer levels were significantly different from those in survivors. A random forest model indicated that the most important feature was PT followed by D-dimer, indicating their positive associations with disease severity. Autopsy of deceased patients fulfilling diagnostic criteria for DIC revealed microthromboses in multiple organs. CONCLUSIONS: Combining autopsy data, time-sequential changes and statistical methods to explore hemostasis-relevant indices among the different severities of the disease helps guide therapy and detect prognosis in COVID-19 infection.

18.
TH Open ; 5(1): e43-e55, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1075296

ABSTRACT

COVID-19 (coronavirus disease 2019) patients often show excessive activation of coagulation, associated with increased risk of thrombosis. However, the diagnostic value of coagulation at initial clinical evaluation is not clear. We present an in-depth analysis of coagulation in patients presenting to the emergency department (ED) with suspected COVID-19. N = 58 patients with clinically suspected COVID-19 in the ED were enrolled. N = 17 subsequently tested positive using SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) swabs, while in n = 41 COVID-19 was ruled-out. We analyzed both standard and extended coagulation parameters, including thromboplastin time (INR), activated partial thromboplastin time (aPTT), antithrombin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), D-dimers, and fibrinogen at admission, as well as α2-antiplasmin, activated protein C -resistance, factor V, lupus anticoagulant, protein C, protein S, and von Willebrand diagnostics. These data, as well as mortality and further laboratory parameters, were compared across groups based on COVID-19 diagnosis and severity of disease. In patients with COVID-19, we detected frequent clotting abnormalities, including D-dimers. The comparison cohort in the ED, however, showed similarly altered coagulation. Furthermore, parameters previously shown to distinguish between severe and moderate COVID-19 courses, such as platelets, plasminogen, fibrinogen, aPTT, INR, and antithrombin, as well as multiple nonroutine coagulation analytes showed no significant differences between patients with and without COVID-19 when presenting to the ED. At admission to the ED the prevalence of coagulopathy in patients with COVID-19 is high, yet comparable to the non-COVID-19 cohort presenting with respiratory symptoms. Nevertheless, coagulopathy might worsen during disease progression with the need of subsequent risk stratification.

19.
Eur J Intern Med ; 83: 34-38, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065032

ABSTRACT

BACKGROUND: Many COVID-19 patients develop a hyperinflammatory response which activates blood coagulation and may contribute to the occurrence of thromboembolic complications. Blockade of interleukin-6, a key cytokine in COVID-19 pathogenesis, may improve the hypercoagulable state induced by inflammation. The aim of this study was to evaluate the effects of subcutaneous tocilizumab, a recombinant humanized monoclonal antibody against the interleukin-6 receptor on coagulation parameters. METHODS: Hospitalized adult patients with laboratory-confirmed moderate to critical COVID-19 pneumonia and hyperinflammation, who received a single 324 mg subcutaneous dose of tocilizumab on top of standard of care were enrolled in this analysis. Coagulation parameters were measured before tocilizumab and at day 1, 3, and 7 after treatment. All patients were followed-up for 35 days after admission or until death. RESULTS: 70 patients (mean age 60 years, interquartile range 52-75) were included. Treatment with tocilizumab was associated with a reduction in D-dimer levels (-56%; 95% confidence interval [CI], -68% to -44%), fibrinogen (-48%; 95%CI, -60% to -35%), C-reactive protein (-93%; 95%CI, -99% to -87%), prothrombin time (-4%; 95%CI,-9% to 0.8%), and activated thromboplastin time (-4%; 95%CI,-8.7% to 0.8%), and an increase in platelet count (34%; 95%CI, 23% to 45%). These changes occurred already one day after treatment with sustained reductions throughout day 7. The improvement in coagulation was consistently observed in patients receiving prophylactic or therapeutic dose anticoagulants, and was paralleled by a rapid improvement in respiratory function. CONCLUSIONS: Subcutaneous tocilizumab was associated with significant improvement of blood coagulation parameters independently of thromboprophylaxis dose.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Blood Coagulation/physiology , COVID-19/blood , COVID-19/drug therapy , COVID-19/therapy , Receptors, Interleukin-6/antagonists & inhibitors , Adult , Aged , Blood Cell Count , Blood Coagulation Tests , C-Reactive Protein , Cohort Studies , Combined Modality Therapy , Female , Hospitalization , Humans , Injections, Subcutaneous , Italy , Male , Middle Aged
20.
Food Chem Toxicol ; 148: 111974, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1009497

ABSTRACT

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.


Subject(s)
COVID-19/physiopathology , Hemostasis/drug effects , Heparin/therapeutic use , Thrombosis/complications , Tissue Plasminogen Activator/therapeutic use , Heparin/pharmacology , Humans , Tissue Plasminogen Activator/pharmacology
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