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1.
Signal Transduct Target Ther ; 7(1): 57, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1702971

ABSTRACT

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Lymphopenia/complications , Myocarditis/complications , Pulmonary Embolism/complications , Acute Kidney Injury/drug therapy , Acute Kidney Injury/immunology , Acute Kidney Injury/virology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , COVID-19/virology , Clinical Trials as Topic , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/virology , Endothelial Cells/drug effects , Endothelial Cells/immunology , Endothelial Cells/virology , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/virology , Myocarditis/drug therapy , Myocarditis/immunology , Myocarditis/virology , Pulmonary Embolism/drug therapy , Pulmonary Embolism/immunology , Pulmonary Embolism/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/growth & development , SARS-CoV-2/pathogenicity
2.
Platelets ; 33(1): 48-53, 2022 Jan 02.
Article in English | MEDLINE | ID: covidwho-1541393

ABSTRACT

Coagulopathy is an evident complication of COVID-19 with predominance of a prothrombotic state. Platelet activation plays a key role. The terms "hyper-reactivity" and "hyperactivity" used in recent literature may not be clear or sufficient to explain the pathological events involved in COVID-related thrombosis (CRT). Inflammation may play a bigger role compared to thrombosis in COVID-related mortality because a smaller percentage of patients with COVID-19 die due to direct effects of thrombosis. Not all COVID-19 patients have thrombocytopenia and a few show thrombocytosis. We believe the platelet pathology is more complex than just activation or hyper-activation, particularly due to the platelets' role in inflammation. Understanding the pathology and consequences of platelets' role may help optimize management strategies and diminish CRT-associated morbidity and mortality. In this viewpoint report, we examine the published evidence of platelet hyper-reactivity in COVID-19 with a focused analysis of the key pathologies, diverse alterations, disease outcomes, and therapeutic targets. We believe that COVID-19 is a disease of inflammation and pathologic platelets, and based on the complexity and diverse pathologies, we propose the term "thrombocytopathy" as a more reflective term of the platelets' involvement in COVID-19. In our opinion, thrombocytopathy is the unpredictable pathologic alterations of platelets in function, morphology and number, caused by different factors with a variety of presentations.


Subject(s)
Blood Platelets/pathology , COVID-19/complications , Cytokine Release Syndrome/complications , Disseminated Intravascular Coagulation/complications , Pulmonary Embolism/complications , SARS-CoV-2/pathogenicity , Abciximab/therapeutic use , Acute Disease , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Platelets/drug effects , Blood Platelets/virology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Clopidogrel/therapeutic use , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Fibrinolytic Agents/therapeutic use , Humans , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Platelet Activation/drug effects , Pulmonary Embolism/diagnosis , Pulmonary Embolism/drug therapy , Pulmonary Embolism/virology , Treatment Outcome
3.
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
5.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363677

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
6.
Molecules ; 25(19)2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1302391

ABSTRACT

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Peptides/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory System Agents/therapeutic use , Acute Disease , Anti-Inflammatory Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Betacoronavirus/drug effects , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Host-Pathogen Interactions/drug effects , Humans , Immunologic Factors/chemical synthesis , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Pandemics , Peptides/chemical synthesis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/prevention & control , Respiratory Insufficiency/virology , Respiratory System Agents/chemical synthesis , SARS-CoV-2 , Structure-Activity Relationship
7.
Viruses ; 13(6)2021 06 01.
Article in English | MEDLINE | ID: covidwho-1259619

ABSTRACT

In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , COVID-19/immunology , Clinical Laboratory Techniques , Dexamethasone/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Enoxaparin/therapeutic use , Female , Humans , Middle Aged , SARS-CoV-2/immunology , Vaccination
8.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1206845

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
9.
Minerva Med ; 112(6): 701-712, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1134671

ABSTRACT

INTRODUCTION: Disseminated intravascular coagulation (DIC) has long been understood as a condition where both thrombotic and hemostatic abnormalities coexist. DIC is a difficult complication for clinicians to manage as it is due to multiple underlying complications of pathophysiologic abnormalities in diverse disease states. Ongoing research continues to define the meaning of DIC, evaluate therapeutic options, and how it presents with the complex paradigm of systemic activation of coagulation. In this review we introduce the current topics regarding this difficult situation. EVIDENCE ACQUISITION: Online search of published medical literature through MEDLINE and Web of Science using the term "disseminated intravascular coagulation," "coagulopathy," "coagulation disorder," "hemostasis," "fibrinolysis," "thrombus" and "anticoagulants." EVIDENCE SYNTHESIS: Articles were chosen for inclusion based on their relevance to disseminated intravascular coagulation, coagulopathy, hemostasis and thrombosis in sepsis, COVID-19, trauma, and obstetrics. Reference lists were reviewed to identify additional relevant articles. CONCLUSIONS: DIC is recognized as a pathologically triggered and dysregulated systemic activation of coagulation in response to various noxious stimuli. DIC's phenotype and clinical manifestations can vary from prothrombotic to hemorrhagic, depending on the underlying diseases. However, the fundamental mechanisms of systemic and vascular endothelial dysfunction can be explained as different phases of the acute response, with an initial prothrombotic phase that can commonly change to hemostatic insufficiency. Thrombin is the key initiator of the pathophysiologic process along with endothelial injury and initially fibrinolysis activation followed by fibrinolysis suppression. There is no established approach for managing DIC beyond initially treating the underlying disease and replacement therapy for the management of coagulopathy. Targeting anticoagulation therapy with antithrombin concentrates and recombinant thrombomodulin for the prevention of microthrombus formation, and antifibrinolytic therapy using tranexamic acid for the coagulopathy after massive bleeding, continue to be studied as therapeutic options.


Subject(s)
Blood Coagulation Disorders/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/physiopathology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/physiopathology , Humans
10.
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
11.
Int J Infect Dis ; 104: 568-571, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1083962

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2), a novel coronavirus, originated as an epidemic respiratory illness in Wuhan, China. COVID-19 eventually spread to almost all countries and has now been declared a global pandemic disease by the World Health Organisation. A plethora of research has explored the dynamics of different clinical entities related to SARS-COV-2, in particular, COVID-19 associated coagulopathy. A large scale of patients have been reported to have developed pulmonary embolism without any other standard triggers or risk factors, leading to speculation that COVID-19 is an independent risk factor for venous thromboembolism. In addition to the development of thromboembolic complications such as pulmonary embolism, COVID-19 has also been reported to have triggered disseminated intravascular coagulation (DIC); however, it is unclear whether pulmonary embolism was due to COVID-19-induced thrombosis or a result of coagulopathy secondary to DIC. We describe a unique case of a COVID-19 associated coagulopathy in a patient with confirmed pulmonary embolism along with an overt DIC. Following diagnosis, the challenge was to identify the appropriate treatment modality for this unique situation. The patient was treated with anticoagulants and steroids along with blood products. The patient's condition markedly improved and was clinically stable on discharge.


Subject(s)
COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Pulmonary Embolism/etiology , SARS-CoV-2 , Aged , Anticoagulants/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Female , Humans , Pulmonary Embolism/drug therapy , Risk Factors
12.
Med Intensiva (Engl Ed) ; 45(1): 42-55, 2021.
Article in English, Spanish | MEDLINE | ID: covidwho-1065468

ABSTRACT

During the new pandemic caused by SARS-CoV-2, there is short knowledge regarding the management of different disease areas, such as coagulopathy and interpretation of D-dimer levels, its association with disseminated intravascular coagulation (DIC) and controversy about the benefit of anticoagulation. Thus, a systematic review has been performed to define the role of D-dimer in the disease, the prevalence of DIC and the usefulness of anticoagulant treatment in these patients. A literature search was performed to analyze the studies of COVID-19 patients. Four recommendations were drawn based on expert opinion and scientific knowledge, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The present review suggests the presence of higher levels of D-dimer in those with worse prognosis, there may be an overdiagnosis of DIC in the course of the disease and there is no evidence on the benefit of starting anticoagulant treatment based only on isolated laboratory data.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/blood , COVID-19/blood , Disseminated Intravascular Coagulation/blood , Fibrin Fibrinogen Degradation Products/analysis , SARS-CoV-2 , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/mortality , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/mortality , Critical Illness , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/epidemiology , Humans , Medical Overuse , Observational Studies as Topic , Pandemics , Prevalence , Prognosis
13.
J Neurovirol ; 27(1): 35-51, 2021 02.
Article in English | MEDLINE | ID: covidwho-1061059

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.


Subject(s)
Atherosclerosis/complications , COVID-19/complications , Disseminated Intravascular Coagulation/complications , Hemorrhage/complications , Hyperglycemia/complications , Stroke/complications , Thrombosis/complications , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Atherosclerosis/diagnosis , Atherosclerosis/drug therapy , Atherosclerosis/virology , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Cardiovascular Agents/therapeutic use , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Extracellular Traps/drug effects , Extracellular Traps/immunology , Hemorrhage/diagnosis , Hemorrhage/drug therapy , Hemorrhage/virology , Humans , Hyperglycemia/diagnosis , Hyperglycemia/drug therapy , Hyperglycemia/virology , Inflammation , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/immunology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Stroke/diagnosis , Stroke/drug therapy , Stroke/virology , Thrombosis/diagnosis , Thrombosis/drug therapy , Thrombosis/virology
14.
Thromb Res ; 199: 132-142, 2021 03.
Article in English | MEDLINE | ID: covidwho-1014833

ABSTRACT

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Thrombosis/drug therapy , Thrombosis/etiology , Aged , Aged, 80 and over , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/diagnosis , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
15.
Anaesth Crit Care Pain Med ; 39(3): 351-353, 2020 06.
Article in English | MEDLINE | ID: covidwho-986871
16.
Exp Biol Med (Maywood) ; 246(6): 688-694, 2021 03.
Article in English | MEDLINE | ID: covidwho-971191

ABSTRACT

Acute respiratory disease caused by a novel coronavirus (SARS-CoV-2) has spread all over the world, since its discovery in 2019, Wuhan, China. This disease is called COVID-19 and already killed over 1 million people worldwide. The clinical symptoms include fever, dry cough, dyspnea, headache, dizziness, generalized weakness, vomiting, and diarrhea. Unfortunately, so far, there is no validated vaccine, and its management consists mainly of supportive care. Venous thrombosis and pulmonary embolism are highly prevalent in patients suffering from severe COVID-19. In fact, a prothrombotic state seems to be present in most fatal cases of the disease. SARS-CoV-2 leads to the production of proinflammatory cytokines, causing immune-mediated tissue damage, disruption of the endothelial barrier, and uncontrolled thrombogenesis. Thrombin is the key regulator of coagulation and fibrin formation. In severe COVID-19, a dysfunctional of physiological anticoagulant mechanisms leads to a progressive increase of thrombin activity, which is associated with acute respiratory distress syndrome development and a poor prognosis. Protease-activated receptor type 1 (PAR1) is the main thrombin receptor and may represent an essential link between coagulation and inflammation in the pathophysiology of COVID-19. In this review, we discuss the potential role of PAR1 inhibition and regulation in COVID-19 treatment.


Subject(s)
Blood Coagulation/physiology , COVID-19/pathology , Disseminated Intravascular Coagulation/pathology , Receptor, PAR-1/metabolism , Thrombin/metabolism , Anticoagulants/therapeutic use , Blood Coagulation/drug effects , Blood Coagulation Factors/metabolism , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Humans , Pulmonary Embolism/pathology , Pulmonary Embolism/prevention & control , Receptor, PAR-1/antagonists & inhibitors , Receptors, Cell Surface/metabolism , SARS-CoV-2 , Venous Thrombosis/pathology , Venous Thrombosis/prevention & control
17.
Am J Cardiovasc Drugs ; 20(6): 559-570, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-910261

ABSTRACT

In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk-benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.


Subject(s)
Anticoagulants/pharmacology , Anticoagulants/therapeutic use , COVID-19/complications , Thrombosis/etiology , Thrombosis/prevention & control , Age Factors , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anticoagulants/administration & dosage , Anticoagulants/classification , Antiviral Agents/pharmacology , Atrial Fibrillation/drug therapy , Chemoprevention/adverse effects , Chemoprevention/methods , Disseminated Intravascular Coagulation/drug therapy , Drug Interactions , Humans , Italy , Pandemics , Risk Factors , Risk Management , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Thrombosis/drug therapy , Thrombosis/physiopathology
18.
Int J Infect Dis ; 102: 529-531, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-898988

ABSTRACT

Nafamostat, a serine proteinase inhibitor with various actions including antithrombin, antiplasmin, and antitrypsin effects, has been used in clinical practice to treat disseminated intravascular coagulation (DIC) and pancreatitis. This case report describes the clinical course of a patient with COVID-19 pneumonia whose severe hypoxemia, probably caused by DIC and pulmonary embolism, showed remarkable improvement with combination heparin and nafamostat therapy. In addition, beneficial mechanisms of nafamostat against COVID-19 and the necessity of attention to hyperkalemia as an adverse effect are discussed.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/complications , Disseminated Intravascular Coagulation/drug therapy , Guanidines/administration & dosage , Aged , Benzamidines , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/virology , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/virology , Humans , Male , SARS-CoV-2/physiology
19.
Blood Rev ; 47: 100761, 2021 05.
Article in English | MEDLINE | ID: covidwho-837100

ABSTRACT

COVID-19 has become a pandemic in the United States and worldwide. COVID-19-induced coagulopathy (CIC) is commonly encountered at presentation manifested by considerable elevation of D-dimer and fibrin split products but with modest or no change in activated partial thromboplastin time and prothrombin time. CIC is a complex process that is distinctly different from conventional sepsis-induced coagulopathy. The cytokine storm induced by COVID-19 infection appears to be more severe in COVID-19, resulting in development of extensive micro- and macrovascular thrombosis and organ failure. Unlike conventional sepsis, anticoagulation plays a key role in the treatment of COVID-19, however without practice guidelines tailored to these patients. We propose a scoring system for COVID-19-coagulopathy (CIC Scoring) and stratification of patients for the purpose of anticoagulation therapy based on risk categories. The proposed scoring system and therapeutic guidelines are likely to undergo revisions in the future as new data become available in this evolving field.


Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation/drug effects , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Thrombosis/drug therapy , Animals , COVID-19/blood , COVID-19/complications , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Fibrin Fibrinogen Degradation Products/analysis , Humans , SARS-CoV-2/isolation & purification , Thrombosis/blood , Thrombosis/etiology
20.
Rev Med Virol ; 31(3): e2180, 2021 05.
Article in English | MEDLINE | ID: covidwho-815926

ABSTRACT

BACKGROUND: Coagulopathy and thromboembolic events are common in Covid-19 patients and are poor prognostic factors. Controversy exists regarding the potential of anticoagulation (AC) to reduce mortality and incidence of thromboembolic events in Covid-19 patients. The current systematic review and meta-analysis investigated the association between anticoagulants and mortality in adult hospitalized COVID-19 patients using the available published non-randomized studies. METHODS: Google Scholar, PubMed, Scopus, the Cochrane Library and Clinical Trials.gov were searched for relevant studies. A meta-analysis of adjusted and unadjusted estimates was performed. The relative risk was used as a measure of effect. The random-effects model was used to pool estimates using the generic inverse variance method. RESULTS: Sixteen studies were included in the quantitative data synthesis. Results showed a statistically significant association between AC and mortality (RR = 0.56, 95% CI 0.36; 0.92, p = 0.02). Both therapeutic (Relative risk [RR] = 0.4, 95% CI 0.27; 0.57) and prophylactic AC (RR = 0.54, 95% CI 0.41; 0.71) were associated with lower risk of mortality. Pre-admission AC was not associated with mortality (RR = 0.84, 95% CI 0.49; 1.43, p > 0.05) while prophylactic AC was associated with higher risk of mortality compared to therapeutic AC (RR = 1.58, 95% CI 1.34; 1.87, p < 0.001). CONCLUSION: Findings support the association of AC with mortality in Covid-19 patients. The results, synthesized from mostly low-quality studies, show that prophylactic and therapeutic AC might reduce mortality in Covid-19 patients. Findings suggest that therapeutic doses might be associated with better survival compared to prophylactic doses.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , COVID-19/blood , COVID-19/mortality , COVID-19/pathology , Case-Control Studies , Cohort Studies , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/pathology , Drug Administration Schedule , Hospitalization , Humans , Odds Ratio , Pre-Exposure Prophylaxis/methods , Pulmonary Embolism/blood , Pulmonary Embolism/mortality , Pulmonary Embolism/pathology , Risk , SARS-CoV-2/metabolism , Survival Analysis , Treatment Outcome
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