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2.
Thromb Res ; 213 Suppl 1: S72-S76, 2022 05.
Article in English | MEDLINE | ID: covidwho-1867825

ABSTRACT

Cancer patients are at risk for a more severe COVID-19 infection as well as an adverse outcome of such infection. This may be caused by the cancer itself (e.g haematological malignancies and lung cancer) or due to immune suppression caused by anti-cancer treatment. Severe COVID-19 infections are often complicated by a coagulopathy that clinically results in a high incidence of venous thromboembolic disease. Cancer itself is associated with a hypercoagulable state and a markedly increased incidence of thromboembolic complications, hence the combination of cancer and COVID-19 may amplify this risk. COVID-19 vaccination seems safe and effective in most cancer patients although adapted and bespoke vaccination schemes may increase the seroconversion rate and immune response in selected patients. Specific management strategies to improve outcomes of cancer patients in COVID-19 (e.g. higher intensity antithrombotic prophylaxis) are lacking and should be evaluated in clinical studies simultaneously focusing on efficacy and safety.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Neoplasms , Thromboembolism , Thrombosis , Anticoagulants/therapeutic use , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , COVID-19/complications , COVID-19 Vaccines , Fibrin Fibrinogen Degradation Products/therapeutic use , Fibrinolytic Agents/therapeutic use , Humans , Neoplasms/drug therapy , Neoplasms/therapy , SARS-CoV-2 , Thromboembolism/drug therapy , Thrombosis/drug therapy
4.
Anaesthesist ; 70(8): 662-670, 2021 Aug.
Article in German | MEDLINE | ID: covidwho-1575534

ABSTRACT

BACKGROUND: In the context of sepsis and septic shock, coagulopathy often occurs due to the close relationship between coagulation and inflammation. Sepsis-induced coagulopathy (SIC) is the most severe and potentially fatal form. Anticoagulants used in prophylactic or therapeutic doses are discussed to potentially exert beneficial effects in patients with sepsis and/or SIC; however, due to the lack of evidence recent guidelines are limited to recommendations for drug prophylaxis of venous thromboembolism (VTE), while treatment of SIC has not been addressed. METHODS: In order to determine the status quo of VTE prophylaxis as well as treatment of SIC in German intensive care units (ICU), we conducted a Germany-wide online survey among heads of ICUs from October 2019 to May 2020. In April 2020, the survey was supplemented by an additional block of questions on VTE prophylaxis and SIC treatment in coronavirus disease 2019 (COVID-19) patients. RESULTS: A total of 67 senior doctors took part in the survey. The majority (n = 50; 74.6%) of the responses were from ICU under the direction of an anesthesiologist and/or a department of anesthesiology. Most of the participants worked either at a university hospital (n = 31; 47.8%) or an academic teaching hospital (n = 27; 40.3%). The survey results show a pronounced heterogeneity in clinical practice with respect to the prophylaxis of VTE as well as SIC treatment. In an exemplary case of pneumogenic sepsis, low molecular weight heparins (LMWH) were by far the most frequently mentioned group of medications (n = 51; 76.1% of the responding ITS). In the majority of cases (n = 43; 64.2%), anti-FXa activity is not monitored with the use of LMWH in prophylaxis doses. Unfractionated heparin (UFH) was listed as a strategy for VTE prophylaxis in 37.3% of the responses (n = 25). In an exemplary case of abdominal sepsis 54.5% of the participants (n = 36; multiple answers possible) stated the use of UFH or LMWH and UFH with dosage controlled by PTT is used on two participating ICUs. The anti-FXa activity under prophylactic anticoagulation with LMWH is monitored in 7 participating clinics (10.6%) in abdominal sepsis. Systematic screening for sepsis-associated coagulation disorders does not take place in most hospitals and patterns in the use of anticoagulants show significant variability between ICUs. In the case of COVID-19 patients, it is particularly noticeable that in three quarters of the participating ICUs the practice of drug-based VTE prophylaxis and SIC treatment does not differ from that of non-COVID-19 patients. CONCLUSION: The heterogeneity of answers collected in the survey suggests that a systematic approach to this topic via clinical trials is urgently needed to underline individualized patient care with the necessary evidence.


Subject(s)
Anticoagulants , Blood Coagulation Disorders , Heparin, Low-Molecular-Weight/therapeutic use , Sepsis , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19 , Germany , Heparin/therapeutic use , Humans , Intensive Care Units , Sepsis/complications
5.
Nutrients ; 13(12)2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542693

ABSTRACT

Bromelain is a major sulfhydryl proteolytic enzyme found in pineapple plants, having multiple activities in many areas of medicine. Due to its low toxicity, high efficiency, high availability, and relative simplicity of acquisition, it is the object of inexhaustible interest of scientists. This review summarizes scientific reports concerning the possible application of bromelain in treating cardiovascular diseases, blood coagulation and fibrinolysis disorders, infectious diseases, inflammation-associated diseases, and many types of cancer. However, for the proper application of such multi-action activities of bromelain, further exploration of the mechanism of its action is needed. It is supposed that the anti-viral, anti-inflammatory, cardioprotective and anti-coagulatory activity of bromelain may become a complementary therapy for COVID-19 and post-COVID-19 patients. During the irrepressible spread of novel variants of the SARS-CoV-2 virus, such beneficial properties of this biomolecule might help prevent escalation and the progression of the COVID-19 disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Bromelains/therapeutic use , COVID-19/drug therapy , Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Neoplasms/drug therapy , Plant Proteins/therapeutic use , SARS-CoV-2 , Ananas/enzymology , Anti-Inflammatory Agents/chemistry , Anticoagulants/chemistry , Bromelains/chemistry , Cardiotonic Agents/chemistry , Fibrinolysis/drug effects , Humans , Plant Proteins/chemistry
6.
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.
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
8.
Viruses ; 13(10)2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438739

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.


Subject(s)
COVID-19/complications , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/physiopathology , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Blood Coagulation Disorders/drug therapy , COVID-19/drug therapy , Endothelial Cells , Factor Xa Inhibitors/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inflammation/drug therapy , Male , Middle Aged , SARS-CoV-2/pathogenicity , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/immunology , Thrombosis/drug therapy , Thrombosis/immunology
9.
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
10.
Clin Res Cardiol ; 111(3): 322-332, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1427245

ABSTRACT

AIMS: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients. METHODS AND RESULTS: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056). CONCLUSIONS: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , COVID-19/mortality , SARS-CoV-2/drug effects , Thromboembolism/drug therapy , Aged , Blood Coagulation Disorders/virology , Comorbidity , Europe , Female , Humans , Male , Middle Aged , Retrospective Studies , Thromboembolism/virology
11.
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
12.
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
13.
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
14.
Expert Opin Ther Targets ; 25(6): 423-433, 2021 06.
Article in English | MEDLINE | ID: covidwho-1281815

ABSTRACT

INTRODUCTION: Defibrotide (DF) is a polyribonucleotide with antithrombotic, pro-fibrinolytic, and anti-inflammatory effects on endothelium. These effects and the established safety of DF present DF as a strong candidate to treat viral and post-infectious syndromes involving endothelial dysfunction. AREAS COVERED: We discuss DF and other therapeutic agents that have the potential to target endothelial components of pathogenesis in viral and post-infectious syndromes. We introduce defibrotide (DF), describe its mechanisms of action, and explore its established pleiotropic effects on the endothelium. We describe the established pathophysiology of Coronavirus Disease 2019 (COVID-19) and highlight the processes specific to COVID-19 potentially modulated by DF. We also present influenza A and viral hemorrhagic fevers, especially those caused by hantavirus, Ebola virus, and dengue virus, as viral syndromes in which DF might serve therapeutic benefit. Finally, we offer our opinion on novel treatment strategies targeting endothelial dysfunction in viral infections and their severe manifestations. EXPERT OPINION: Given the critical role of endothelial dysfunction in numerous infectious syndromes, in particular COVID-19, therapeutic pharmacology for these conditions should increasingly prioritize endothelial stabilization. Several agents with endothelial protective properties should be further studied as treatments for severe viral infections and vasculitides, especially where other therapeutic modalities have failed.


Subject(s)
COVID-19/complications , Endothelium, Vascular/drug effects , Polydeoxyribonucleotides/pharmacology , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19/physiopathology , COVID-19/virology , Endothelium, Vascular/physiopathology , Humans , Polydeoxyribonucleotides/therapeutic use , SARS-CoV-2/isolation & purification
15.
Sci Rep ; 11(1): 13325, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1281739

ABSTRACT

COVID 19 is associated with a hypercoagulable state and frequent thromboembolic complications. For how long this acquired abnormality lasts potentially requiring preventive measures, such as anticoagulation remains to be delineated. We used viscoelastic rotational thrombelastometry (ROTEM) in a single center cohort of 13 critical ill patients and performed follow up examinations three months after discharge from ICU. We found clear signs of a hypercoagulable state due to severe hypofibrinolysis and a high rate of thromboembolic complications during the phase of acute illness. Three month follow up revealed normalization of the initial coagulation abnormality and no evidence of venous thrombosis in all thirteen patients. In our cohort the coagulation profile was completely normalized three months after COVID-19. Based on these findings, discontinuation of anticoagulation can be discussed in patients with complete venous reperfusion.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders , COVID-19 , Thrombelastography , Thromboembolism , Venous Thrombosis , Aged , Blood Coagulation , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/pathology , COVID-19/blood , COVID-19/drug therapy , COVID-19/pathology , Cohort Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index , Thromboembolism/drug therapy , Thromboembolism/pathology , Venous Thrombosis/drug therapy , Venous Thrombosis/pathology
16.
Anaesthesiol Intensive Ther ; 53(2): 153-161, 2021.
Article in English | MEDLINE | ID: covidwho-1234881

ABSTRACT

Patients hospitalized in the intensive care unit (ICU) due to the COVID-19 experience a high incidence (up to 43%) of venous thromboembolic events. While laboratory findings in COVID-19-associated coagulopathy (CAC) show increased D-dimer and fibrinogen levels, the abnormalities in standard coagulation tests and platelet count are minimal. Recent studies suggest contribution of fibrinolysis shutdown to this phenomenon. Endothelial injury and alteration of its antithrombotic activity can lead to micro- and macrovascular thrombosis in the lungs, occurrence of which is associated with poor clinical outcome in critically ill patients with COVID-19. Additionally, the hypercoagulability induced by activation of coagulation pathways during the immune response to SARS-CoV-2 infection contributes to impaired organ perfusion. This, alongside with hypoxemia, leads to multiorgan failure. Various diagnostic regimens, some of which include global assays of haemostasis, are currently being published and discussed. Numerous guidelines and recommendations of scientific societies and groups of specialists have been published. However, there is no single optimal algorithm for anticoagulation treatment and monitoring specific to the ICU patients with COVID-19. The authors have attempted to summarize the data related to CAC and thrombotic disease and develop an algorithm consistent with the latest clinical practice guideline recommendations.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , COVID-19/complications , Algorithms , Blood Coagulation/drug effects , COVID-19/drug therapy , Female , Humans , Intensive Care Units , Male , Thrombosis/etiology , Thrombosis/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control
17.
Am J Case Rep ; 22: e930667, 2021 May 10.
Article in English | MEDLINE | ID: covidwho-1222298

ABSTRACT

BACKGROUND Coronavirus Disease 2019 (COVID-19) has been associated with a hypercoagulability state. Clinical presentation can range from asymptomatic to severe illness and mortality. Thrombotic complications in COVID-19 have been associated with mortality. The incidence of systemic hypercoagulation in COVID-19 is associated with the process of severe inflammation. The majority of severely ill patients have developed coagulopathy, and this condition is associated with poor outcomes. CASE REPORT A 72-year-old man presented with respiratory symptoms and was diagnosed with a COVID-19 infection. He presented with tachypnea, tachycardia, increased blood pressure, and 74% peripheral oxygen saturation under 15 L/min oxygen per non-rebreather mask. Initial laboratory test results showed severe hypoxemia as per blood gas analysis (pH 7.42, pCO2 23 mmHg, pO2 43 mmHg, HCO3 15 mmol/L, base deficit -9 mmol/L), with increased procalcitonin, high-sensitivity C-reactive protein, D-dimer, fibrinogen, creatine kinase myocardial band, and Troponin I. He subsequently developed thrombosis of the pulmonary arteries and multiple branches of the pulmonary vein despite therapeutic anticoagulation. We initiated heparin therapy (average dose 25 191 units per day, mean activated partial thromboplastin time, 64.35 seconds). Radiological investigations revealed multiple thromboses on pulmonary arteries and pulmonary veins, as well as multiple locations of brain infarction. Rescue thrombolytic therapy was given, but unfortunately, the patient died due to multiple end-organ failures. CONCLUSIONS Controlling coagulopathy, and thrombolytic therapy type and timing, are critical issues, and new strategies must be sought to lower its morbidity and mortality rates further.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Aged , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , Humans , Male , SARS-CoV-2 , Thrombolytic Therapy
18.
Cell Biol Int ; 45(9): 1832-1850, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1212726

ABSTRACT

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of ß-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , COVID-19/pathology , Blood Coagulation Disorders/etiology , Blood Platelets/cytology , Blood Platelets/metabolism , COVID-19/complications , COVID-19/virology , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inflammation/etiology , SARS-CoV-2/isolation & purification , Thromboembolism/drug therapy , Thromboembolism/etiology
19.
Lancet Haematol ; 8(7): e524-e533, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1208801

ABSTRACT

COVID-19 is associated with a high incidence of thrombotic complications, which can be explained by the complex and unique interplay between coronaviruses and endothelial cells, the local and systemic inflammatory response, and the coagulation system. Empirically, an intensified dose of thrombosis prophylaxis is being used in patients admitted to hospital with COVID-19 and several guidelines on this topic have been published, although the insufficiency of high quality and direct evidence has led to weak recommendations. In this Viewpoint we summarise the pathophysiology of COVID-19 coagulopathy in the context of patients who are ambulant, admitted to hospital, and critically ill or non-critically ill, and those post-discharge from hospital. We also review data from randomised controlled trials in the past year of antithrombotic therapy in patients who are critically ill. These data provide the first high-quality evidence on optimal use of antithrombotic therapy in patients with COVID-19. Pharmacological thromboprophylaxis is not routinely recommended for patients who are ambulant and post-discharge. A first ever trial in non-critically ill patients who were admitted to hospital has shown that a therapeutic dose of low-molecular-weight heparin might improve clinical outcomes in this population. In critically ill patients, this same treatment does not improve outcomes and prophylactic dose anticoagulant thromboprophylaxis is recommended. In the upcoming months we expect numerous data from the ongoing antithrombotic COVID-19 studies to guide clinicians at different stages of the disease.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/physiopathology , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Aged , Aged, 80 and over , Blood Coagulation/physiology , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Critical Illness/therapy , Endothelial Cells/pathology , Endothelial Cells/virology , Hospitalization , Humans , Incidence , Outcome Assessment, Health Care , Patient Discharge/standards , Randomized Controlled Trials as Topic , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/physiopathology , Venous Thromboembolism/prevention & control
20.
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
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