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1.
Sovrem Tekhnologii Med ; 12(5): 6-16, 2021.
Article in English | MEDLINE | ID: covidwho-1527051

ABSTRACT

The aim of the investigation was to study the clinical course of COVID-19 in the presence of diabetes mellitus (DM) and elucidate possible mechanisms of their mutual aggravation. Materials and Methods: The study included 64 patients with COVID-19; of them, 32 were with DM (main group) and 32 were DM-free (control group). The groups were formed according to the "case-control" principle. During hospitalization, the dynamics of clinical, glycemic, and coagulation parameters, markers of systemic inflammation, as well as kidney and liver functions were monitored and compared. Results: Among patients with DM, the course of viral pneumonia was more severe, as evidenced by a 2.2-fold higher number of people with extensive (>50%) lung damage (p=0.05), an increased risk of death according to the CURB-65 algorithm (1.3-fold, p=0.043), and a longer duration of insufficient blood oxygen saturation (p=0.0004). With the combination of COVID-19 and DM, hyperglycemia is persistent, without pronounced variability (MAGE - 1.5±0.6 mmol/L), the levels of C-reactive protein (p=0.028), creatinine (p=0.035), and fibrinogen (p=0.013) are higher, manifestations of hypercoagulability persist longer, including slower normalization of antithrombin III (p=0.012), fibrinogen (p=0.037), and D-dimer (p=0.035). Conclusion: The course of COVID-19 in patients with DM is associated with a high severity and extension of pneumonia, persistent decrease in oxygen supply, high hyperglycemia, accelerated renal dysfunction, systemic inflammation, and hypercoagulability.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Diabetes Mellitus , Blood Coagulation Disorders/epidemiology , Humans , Inflammation , SARS-CoV-2
2.
Front Immunol ; 12: 738093, 2021.
Article in English | MEDLINE | ID: covidwho-1518484

ABSTRACT

Disease caused by SARS-CoV-2 coronavirus (COVID-19) led to significant morbidity and mortality worldwide. A systemic hyper-inflammation characterizes severe COVID-19 disease, often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. Flow cytometry and next-generation sequencing were done on peripheral blood cells and urokinase-type plasminogen activator receptor (suPAR), and cytokines were measured from and mass spectrometry-based proteomics was done on plasma samples from an Indian cohort of COVID-19 patients. Publicly available single-cell RNA sequencing data were analyzed for validation of primary data. Statistical analyses were performed to validate risk stratification. We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcomes, in terms of both survival benefit (hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus, we identified suPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.


Subject(s)
COVID-19/blood , Receptors, Urokinase Plasminogen Activator/blood , SARS-CoV-2 , Adult , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/immunology , Blood Proteins/analysis , COVID-19/immunology , Cytokines/blood , Humans , Inflammation/blood , Inflammation/immunology , Middle Aged , Myeloid Cells/immunology , Proteome/analysis , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/immunology , Severity of Illness Index , Young Adult
3.
Dtsch Med Wochenschr ; 146(13-14): 899-903, 2021 Jul.
Article in German | MEDLINE | ID: covidwho-1493267

ABSTRACT

Infection with SARS-CoV-2 has a profound influence on the hematopoetic system that mediates clinical symptoms and mortality. Several studies have shown that treatment of the cytokine storm (CRS) with anti-inflammatory drugs like dexamethasone and tocilizumab can significantly improve survival. Systematic reviews confirm the safety of convalescent plasma administration and offer initial indications of its effectiveness in certain groups. COVID-associated coagulopathy (CAC) and vaccine-induced immune thrombotic thrombocytopenia (VITT) represent severe infection- or vaccination associated complications that require a specific diagnostic and therapeutic workup.


Subject(s)
COVID-19/blood , COVID-19/complications , Hematology , Hematopoiesis , Hemostasis , SARS-CoV-2/physiology , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/therapy , COVID-19/mortality , COVID-19/therapy , Humans , Immunization, Passive
4.
Hamostaseologie ; 41(5): 387-396, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1483190

ABSTRACT

Hypercoagulability and vascular injury, which characterize morbidity in COVID-19 disease, are frequently observed in the skin. Several pathomechanisms, such as inflammation caused by angiotensin-converting enzyme 2-mediated uptake into endothelial cells or SARS-CoV-2-initiated host immune responses, contribute to microthrombus formation and the appearance of vascular skin lesions. Besides pathophysiologic mechanisms observed in the skin, this review describes the clinical appearance of cutaneous vascular lesions and their association with COVID-19 disease, including acro-ischemia, reticular lesions, and cutaneous small vessel vasculitis. Clinicians need to be aware that skin manifestations may be the only symptom in SARS-CoV-2 infection, and that inflammatory and thrombotic SARS-CoV-2-driven processes observed in multiple organs and tissues appear identically in the skin as well.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Skin/blood supply , Angiotensin-Converting Enzyme 2/physiology , Antibodies, Antiphospholipid/blood , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/pathology , COVID-19/pathology , COVID-19/physiopathology , Complement Activation , Cytokines/metabolism , Host Microbial Interactions/immunology , Host Microbial Interactions/physiology , Humans , Microvessels/immunology , Microvessels/pathology , Microvessels/physiopathology , Pandemics , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Skin/immunology , Vasculitis/etiology , Vasculitis/pathology , Vasculitis/physiopathology , Virus Internalization
5.
Int J Mol Sci ; 22(21)2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1480798

ABSTRACT

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.


Subject(s)
Amides/therapeutic use , Blood Coagulation Disorders/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Ethanolamines/therapeutic use , Palmitic Acids/therapeutic use , Sepsis/complications , Amides/chemistry , Amides/pharmacology , Animals , Blood Coagulation Disorders/etiology , COVID-19/pathology , COVID-19/virology , Cytokines/blood , Cytokines/metabolism , Disease Models, Animal , Disseminated Intravascular Coagulation/etiology , Ethanolamines/chemistry , Ethanolamines/pharmacology , Fibrin Fibrinogen Degradation Products/metabolism , Lipopolysaccharides/toxicity , Lung/metabolism , Lung/pathology , Male , Mast Cells/cytology , Mast Cells/drug effects , Mast Cells/metabolism , Palmitic Acids/chemistry , Palmitic Acids/pharmacology , Partial Thromboplastin Time , Prothrombin Time , Rats , Rats, Sprague-Dawley , SARS-CoV-2/isolation & purification , Sepsis/pathology , Serine Proteases/metabolism
7.
Eur Rev Med Pharmacol Sci ; 25(19): 5904-5912, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1478932

ABSTRACT

OBJECTIVE: Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection. PATIENTS AND METHODS: Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy. RESULTS: The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen. CONCLUSIONS: In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.


Subject(s)
Blood Coagulation Disorders/pathology , COVID-19/pathology , Liver Diseases/pathology , Liver/pathology , Thrombosis/pathology , Aged , Autopsy , Biopsy , Erythrocytes/pathology , Fibrin , Hepatocytes/pathology , Humans , Male , Microscopy, Electron, Scanning , Middle Aged , Thrombosis/complications , Young Adult
8.
Int J Biol Macromol ; 193(Pt A): 948-955, 2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1471998

ABSTRACT

The severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) keeps on destroying normal social integrity worldwide, bringing about extraordinary medical services, cultural and financial interruption. Individuals with diabetes have been demonstrated to be at higher risk of complications and even death when exposed to SARS-CoV-2. Regardless of pandemic scale infection, there is presently limited comprehension on the potential impact of SARS-CoV-2 on individuals with diabetes. Human serum albumin (HSA) is the most abundant circulating plasma protein in human serum and attracted more interest from researchers because most susceptible to non-enzymatic glycation reactions. Albumin down-regulates the expression of ACE2 that is the target receptor of COVID-19. Hypoalbuminemia, coagulopathy, and vascular disease have been connected in COVID-19 and appear to predict outcomes independent of age and morbidity. This review discusses the most recent evidence that the ACE/ACE2 ratio could influence by human serum albumin both the susceptibility of individuals to SARS-CoV-2 infection and the outcome of the COVID-19 disease.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19 , SARS-CoV-2/metabolism , Serum Albumin, Human/metabolism , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/therapy , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Disease Susceptibility , Humans , Vascular Diseases/blood , Vascular Diseases/diagnosis , Vascular Diseases/therapy
9.
Indian J Med Res ; 153(5&6): 606-618, 2021.
Article in English | MEDLINE | ID: covidwho-1468588

ABSTRACT

The ongoing pandemic of novel coronavirus 2019 is rapidly evolving, and newer organ- and system-specific manifestations are being observed. Thrombotic complications and coagulopathy are frequent manifestations of the disease, especially in sick patients, which appear to be unique and distinct from sepsis-induced coagulopathy, disseminated intravascular coagulation and other viral infection-induced coagulation abnormalities. Elevated D-dimers and fibrinogen in the early stage of the disease with minimally deranged prothrombin time and platelet counts are prominent and distinguishing features. Venous and arterial thromboses, as opposed to bleeding events, are the major clinical correlates. There is much to be known about the pathogenesis of COVID-associated coagulopathy; however, the mechanisms overlap with thrombotic microangiopathy, haemophagocytic syndrome and antiphospholipid syndrome compounded by the diffuse endothelial damage. The recommendations regarding the treatment are still evolving, but antithrombotic therapy has a definite role in positive outcomes of sick patients.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Venous Thromboembolism , Anticoagulants , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/epidemiology , Humans , SARS-CoV-2
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1582-1588, 2021 Oct.
Article in Chinese | MEDLINE | ID: covidwho-1464140

ABSTRACT

AbstractObjective: To analyze the liver injury and coagulation dysfunction in COVID-19 severe/critical type patients. METHODS: The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test. RESULTS: Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27-80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05). CONCLUSION: In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Aged , Aged, 80 and over , Female , Humans , Liver , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
11.
Anaesthesist ; 70(2): 121-126, 2021 Feb.
Article in German | MEDLINE | ID: covidwho-1453674

ABSTRACT

A 59-year-old male patient was admitted to hospital diagnosed with moderate pneumonia associated with COVID-19. Upfront treatment with hydroxychloroquine and azithromycin was started. Due to a clinical deterioration (ARDS, circulatory shock) and greatly increased inflammation markers 6 days after admission, a cytokine storm was suspected and off-label treatment with the IL­6 receptor antagonist tocilizumab was initiated. Subsequently there was a dramatic rise of D­dimers indicating pulmonary intravascular coagulopathy and respiratory insufficiency worsened. After a second dose of tocilizumab was administered severe perimyocarditis with cardiac arrhythmia, hemodynamic instability and ST elevation occurred. Shortly afterwards the patient died due to multiorgan failure. From our experience, exacerbation of COVID-19 following treatment with tocilizumab cannot be ruled out. Randomized controlled studies are necessary to further investigate the efficacy, safety and patient selection criteria for tocilizumab treatment in COVID-19.


Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Blood Coagulation Disorders/etiology , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Myocarditis/etiology , Receptors, Interleukin-6/antagonists & inhibitors , Fatal Outcome , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Off-Label Use , Respiratory Distress Syndrome/etiology , Respiratory Insufficiency , Treatment Outcome
13.
Int J Pharm ; 608: 121122, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1433361

ABSTRACT

Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.


Subject(s)
Blood Coagulation Disorders/drug therapy , COVID-19 , Dry Powder Inhalers , Pyridines/administration & dosage , Thiazoles/administration & dosage , Administration, Inhalation , Aerosols , Blood Coagulation Disorders/virology , COVID-19/complications , Humans , Particle Size , Powders
14.
Rinsho Ketsueki ; 62(8): 1236-1246, 2021.
Article in Japanese | MEDLINE | ID: covidwho-1404087

ABSTRACT

In 2020, infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rapidly spread across the world to become a global pandemic. Coronavirus disease-2019 (COVID-19) is associated with a high rate of coagulopathy and thrombotic complications. The underlying mechanisms involved in these processes are complex. In addition to the low physical activity, blood coagulation activation accompanied by excessive immune/inflammatory reactions and vascular endothelialitis associated with the presence of intracellular SARS-CoV-2 and disrupted cell membranes contribute substantially to the complexity of the mechanisms. The types of thrombosis that occur include arterial thrombosis and venous thromboembolism. Microthrombi in alveolar capillaries are observed in COVID-19 patients. Considering the possible involvement of thrombosis in the worsening of COVID-19, prophylactic anticoagulant therapy, such as low-molecular-weight heparin or unfractionated heparin, is essential for patients with moderate and severe infections. Even with prophylactic anticoagulant therapy, the incidence of thrombosis remains high. Consequently, control of the underlying inflammation and vascular endothelial protection may be required in combination with anticoagulant therapy.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Anticoagulants , Heparin , Humans , Pandemics , SARS-CoV-2
16.
Sci Rep ; 11(1): 16290, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1354111

ABSTRACT

To reveal if coagulopathies relate to the course of COVID-19, we examined 255 patients with moderate and severe COVID-19, receiving anticoagulants and immunosuppressive drugs. Coagulopathy manifested predominantly as hypercoagulability that correlated directly with systemic inflammation, disease severity, comorbidities, and mortality risk. The prolonged clotting tests in about » of cases were associated with high levels of C-reactive protein and antiphospholipid antibodies, which impeded coagulation in vitro. Contraction of blood clots was hindered in about ½ of patients, especially in severe and fatal cases, and correlated directly with prothrombotic parameters. A decrease in platelet contractility was due to moderate thrombocytopenia in combination with platelet dysfunction. Clots with impaired contraction were porous, had a low content of compressed polyhedral erythrocytes (polyhedrocytes) and an even distribution of fibrin, suggesting that the uncompacted intravital clots are more obstructive but patients could also be prone to bleeding. The absence of consumption coagulopathy suggests the predominance of local and/or regional microthrombosis rather than disseminated intravascular coagulation. The results obtained (i) confirm the importance of hemostatic disorders in COVID-19 and their relation to systemic inflammation; (ii) justify monitoring of hemostasis, including the kinetics of blood clot contraction; (iii) substantiate the active prophylaxis of thrombotic complications in COVID-19.


Subject(s)
Blood Coagulation Disorders/etiology , Blood Platelet Disorders/etiology , COVID-19/complications , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Platelets/ultrastructure , COVID-19/drug therapy , Female , Humans , Inflammation/etiology , Male , Middle Aged , Patient Acuity , Thrombocytopenia/etiology , Treatment Outcome , Young Adult
17.
Dtsch Med Wochenschr ; 146(15): 944-949, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1338575

ABSTRACT

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


Subject(s)
Blood Coagulation Disorders/complications , COVID-19/complications , Thromboembolism/prevention & control , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/prevention & control , Blood Coagulation Disorders/therapy , COVID-19/blood , Humans , Severity of Illness Index , Thromboembolism/etiology
18.
Int J Mol Sci ; 22(15)2021 Jul 26.
Article in English | MEDLINE | ID: covidwho-1325684

ABSTRACT

In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.


Subject(s)
Blood Coagulation Disorders/blood , COVID-19/complications , P-Selectin/blood , Blood Coagulation Disorders/etiology , Blood Platelets/metabolism , Endothelial Cells/metabolism , Humans , Leukocytes/metabolism
19.
J Thromb Haemost ; 18(7): 1747-1751, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317985

ABSTRACT

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/blood , Blood Coagulation , Coronavirus Infections/blood , Pneumonia, Viral/blood , Aged , Anticoagulants/administration & dosage , Biomarkers/blood , Blood Coagulation/drug effects , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/virology , Blood Coagulation Tests , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Fibrinolytic Agents/administration & dosage , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Treatment Outcome
20.
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317980

ABSTRACT

A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation Disorders/drug therapy , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/virology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Fatal Outcome , Female , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Recovery of Function , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
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