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1.
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
2.
Blood Coagul Fibrinolysis ; 32(7): 458-467, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1470186

ABSTRACT

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.


Subject(s)
ADAMTS13 Protein/deficiency , Blood Coagulation , COVID-19/blood , ADAMTS13 Protein/blood , Adult , Aged , COVID-19/complications , Critical Illness/epidemiology , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Sci Rep ; 10(1): 14186, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-1434143

ABSTRACT

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.


Subject(s)
Bacterial Infections/blood , Hemostasis , Partial Thromboplastin Time/methods , Virus Diseases/blood , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Dengue/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Elective Surgical Procedures , Female , Humans , Male , Middle Aged , Procalcitonin/blood , Respiratory Tract Infections/blood
4.
Clin Immunol ; 232: 108852, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401324

ABSTRACT

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.


Subject(s)
Blood Coagulation/physiology , COVID-19/complications , Fibrinolysis/physiology , Inflammation/etiology , Inflammation/virology , Adult , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/metabolism , Blood Coagulation Disorders/pathology , Blood Coagulation Disorders/virology , COVID-19/metabolism , COVID-19/pathology , China , Disease Progression , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/metabolism , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinogen/metabolism , Hemorrhage/etiology , Hemorrhage/pathology , Hemorrhage/virology , Humans , Inflammation/pathology , Male , Middle Aged , Prothrombin Time , SARS-CoV-2/pathogenicity
5.
Hematology ; 26(1): 656-662, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1398020

ABSTRACT

OBJECTIVES: Coagulation dysfunction is an evident factor in the clinical diagnosis and treatment of patients with coronavirus disease 2019 (COVID-19), appearing even in COVID-19 patients with normal inflammation indices. Therefore, this study aimed to analyze the characteristics of coagulation function indices in COVID-19 patients to investigate possible mechanisms through the comparison of non-severe and severe COVID-19 patients. METHODS: We included 143 patients whose clinical characteristics, coagulation function, and other indices such as inflammatory factors were collected and compared based on disease severity. RESULTS: Activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were evidently higher in the severe group than in the non-severe group. Among non-severe COVID-19 patients, the aforementioned indicators depicted increasing trends, but the fibrinogen level alone was higher than normal. However, in severe COVID-19 patients, values of all three indices were higher than normal. In severe COVID-19 patients, fibrinogen and D-dimer were correlated with several inflammation indices during the early stage of the disease. However, no correlation between fibrinogen and inflammatory factors was observed in non-severe COVID-19 patients at any time point. DISCUSSION: Results revealed that the hypercoagulability tendency of severe COVID-19 patients was more evident. The relationship between coagulation function and inflammatory factors showed that changes in coagulation function in severe COVID-19 patients may be related to abnormal increase in inflammatory factors at an early stage; however, in non-severe COVID-19 patients, there might be other factors leading to abnormal coagulation. CONCLUSION: Inflammatory factors were not the only cause of abnormal coagulation function in COVID-19 patients.


Subject(s)
Blood Coagulation , COVID-19/blood , Disseminated Intravascular Coagulation/blood , Thrombophilia/blood , Adult , Aged , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Longitudinal Studies , Male , Middle Aged , Partial Thromboplastin Time , Severity of Illness Index , Thrombophilia/etiology
7.
Int J Lab Hematol ; 43 Suppl 1: 36-42, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1319316

ABSTRACT

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.


Subject(s)
Blood Coagulation Tests , COVID-19/blood , SARS-CoV-2 , Thrombophilia/etiology , Antibodies, Antiphospholipid/blood , Biomarkers/blood , Blood Coagulation Factors/analysis , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Factor Xa/analysis , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Fibrinolysis , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Partial Thromboplastin Time , Platelet Count , Prothrombin Time , Thrombelastography , Thrombin/biosynthesis , Thrombophilia/blood , Thrombophilia/drug therapy
8.
Int J Lab Hematol ; 43 Suppl 1: 29-35, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1319315

ABSTRACT

Vascular endothelial injury is a hallmark of acute infection at both the microvascular and macrovascular levels. The hallmark of SARS-CoV-2 infection is the current COVID-19 clinical sequelae of the pathophysiologic responses of hypercoagulability and thromboinflammation associated with acute infection. The acute lung injury that initially occurs in COVID-19 results from vascular and endothelial damage from viral injury and pathophysiologic responses that produce the COVID-19-associated coagulopathy. Clinicians should continue to focus on the vascular endothelial injury that occurs and evaluate potential therapeutic interventions that may benefit those with new infections during the current pandemic as they may also be of benefit for future pathogens that generate similar thromboinflammatory responses. The current Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) studies are important projects that will further define our management strategies. At the time of writing this report, two mRNA vaccines are now being distributed and will hopefully have a major impact on slowing the global spread and subsequent thromboinflammatory injury we see clinically in critically ill patients.


Subject(s)
COVID-19/complications , Pandemics , SARS-CoV-2 , Thrombophilia/etiology , Vasculitis/etiology , Anticoagulants/therapeutic use , COVID-19/blood , COVID-19/immunology , Child , Disseminated Intravascular Coagulation/etiology , Endothelium, Vascular/injuries , Endothelium, Vascular/physiopathology , Female , Fibrinolysis , Forecasting , Humans , Lung/blood supply , Lung/pathology , Pregnancy , Pregnancy Complications, Infectious/blood , Thromboembolism/etiology , Thromboembolism/prevention & control
9.
Anaesthesiol Intensive Ther ; 53(2): 108-114, 2021.
Article in English | MEDLINE | ID: covidwho-1308509

ABSTRACT

INTRODUCTION: Infection with SARS-CoV-2 in its most severe form leads to acute respiratory distress syndrome requiring mechanical ventilation under the conditions of the Intensive Care Unit (ICU). The state of hypercoagulation described in COVID-19 may deepen respiratory failure, leading to increased mortality. The aim of the presented study is to characterise the haemostatic profile based on the results of clotting system parameters and risk assessment of thromboembolic complications of patients hospitalised in the ICU. MATERIAL AND METHODS: This retrospective study covered the first 10 adult patients hospitalised in the ICU of the Hospital for Infectious Diseases in Warsaw in the second quarter of 2020. Demographic, clinical and laboratory parameters of the coagulation system and the risk of thromboembolic complications were assessed. Well known criteria of haemostatic disorders were used to classify the observed derangements. RESULTS: The most frequently observed deviations in the coagulation system were high concentrations of D-dimer and fibrinogen. In select cases the clotting time was prolonged. No severe thrombocytopenia was observed. All patients presented a high risk of thromboembolic complications as assesed by the Padua score. The observed clotting abnormalities did not meet the criteria for DIC (disseminated intravascular coagulation) and SIC (sepsis-induced coagulopathy) diagnosis. CONCLUSIONS: The main elements of coagulopathy that were observed in our cases differ from those usually seen in patients with recognised sepsis. The unique haemostatic profile of COVID-19 patients treated in the ICU has been described as CAC (COVID-19-associated coagulopathy).


Subject(s)
COVID-19/complications , COVID-19/therapy , Disseminated Intravascular Coagulation/diagnosis , Sepsis/diagnosis , Adult , Blood Coagulation Tests/methods , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Female , Fibrin Fibrinogen Degradation Products/analysis , Humans , Inflammation Mediators/blood , Intensive Care Units , Male , Middle Aged , Poland , Retrospective Studies , Sepsis/blood , Sepsis/etiology
10.
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
11.
Clin Appl Thromb Hemost ; 27: 10760296211021498, 2021.
Article in English | MEDLINE | ID: covidwho-1249538

ABSTRACT

Today the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global health problem. After more than a year with the pandemic, although our knowledge has progressed on COVID-19, there are still many unknowns in virological, pathophysiological and immunological aspects. It is obvious that the most efficient solution to end this pandemic are safe and efficient vaccines. This manuscript summarizes the pathophysiological and thrombotic features of COVID-19 and the safety and efficacy of currently approved COVID-19 vaccines with an aim to clarify the recent concerns of thromboembolic events after COVID-19 vaccination. The influx of newer information is rapid, requiring periodic updates and objective assessment of the data on the pathogenesis of COVID-19 variants and the safety and efficacy of currently available vaccines.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Thrombosis/etiology , Autoantibodies/biosynthesis , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Clinical Trials as Topic , Disseminated Intravascular Coagulation/epidemiology , Disseminated Intravascular Coagulation/etiology , Drug Approval , Female , Genetic Vectors , Glycosaminoglycans/immunology , Humans , Male , Models, Cardiovascular , Pandemics/prevention & control , Platelet Factor 4/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Safety , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/etiology , Thrombosis/epidemiology , Thrombosis/physiopathology , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/genetics , Vaccines, Inactivated/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
12.
Biomolecules ; 11(5)2021 05 06.
Article in English | MEDLINE | ID: covidwho-1223942

ABSTRACT

SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19.


Subject(s)
COVID-19/pathology , Extracellular Traps/metabolism , Thrombosis/immunology , Thrombosis/pathology , Biomarkers/metabolism , COVID-19/immunology , COVID-19/virology , Complement System Proteins/metabolism , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/pathology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/pathology , Humans , Neutrophils/cytology , Neutrophils/immunology , Neutrophils/metabolism , SARS-CoV-2/isolation & purification , Thrombosis/metabolism
13.
J Thromb Thrombolysis ; 52(1): 338-344, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1204923

ABSTRACT

Coronavirus disease (COVID-19) initiates several life-threatening complications including coagulopathies with a unique characteristic that made this problem challenging. Here we presented 4 cases of RT-PCR positive patients that have experienced deadly intraperitoneal hemorrhage with fourth WHO Bleeding Grade after overcoming their respiratory phase. COVID-19 could induce several coagulopathies with different features that besides iatrogenic interventions increases its mortality and morbidity due to lack of clinical evidence based on well-designed randomized clinical trials on anticoagulation therapies (AT) and administration of varieties of newly approved and non-approved medicines. This report showed the urgent need for investigation on the pathophysiology of COVID-19-associated coagulopathy esp. in hemorrhagic events which are needed to make the best therapeutic decision.


Subject(s)
Blood Coagulation , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Hemorrhage/etiology , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/therapy , Fatal Outcome , Hemorrhage/blood , Hemorrhage/diagnosis , Hospital Mortality , Humans , Male , Middle Aged , Peritoneum
15.
N Engl J Med ; 384(22): 2092-2101, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1174739

ABSTRACT

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).


Subject(s)
Autoantibodies/blood , COVID-19 Vaccines/adverse effects , Platelet Factor 4/immunology , Thrombocytopenia/etiology , Thrombosis/etiology , Adult , Autoimmune Diseases/etiology , Blood Chemical Analysis , Disseminated Intravascular Coagulation/etiology , Enzyme-Linked Immunosorbent Assay , Fatal Outcome , Female , Humans , Intracranial Hemorrhages/etiology , Male , Middle Aged , Platelet Activation , Thrombocytopenia/immunology , Thrombosis/immunology , Young Adult
16.
Chin J Traumatol ; 24(2): 63-68, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1093003

ABSTRACT

Throughout the past 2020, the pandemic COVID-19 has caused a big global shock, meanwhile it brought a great impact on the public health network. Trauma emergency system faced a giant challenge and how to manage trauma under the pandemic of COVID-19 was widely discussed. However, the trauma treatment of special population (geriatric patients and patients taking anticoagulant drugs) has received inadequate attention. Due to the high mortality following severe traumatic hemorrhage, hemostasis and trauma-induced coagulopathy are the important concerns in trauma treatment. Sepsis is another topic should not be ignored when we talking about trauma. COVID-19 itself is a special kind of sepsis, and it may even be called as serious systemic infection syndrome. Sepsis has been become a serious problem waiting to be solved urgently no matter in the fields of trauma, or in intensive care and infection, etc. This article reviewed the research progress in areas including trauma emergency care, trauma bleeding and coagulation, geriatric trauma and basic research of trauma within 2020.


Subject(s)
COVID-19 , Emergency Medical Services , Pandemics , Public Health , Trauma Centers , Wounds and Injuries/therapy , Community Networks , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/prevention & control , Disseminated Intravascular Coagulation/therapy , Female , Health Services for the Aged , Hemorrhage/etiology , Hemorrhage/therapy , Hemostasis , Humans , Male , Sepsis/etiology , Sepsis/therapy , Time Factors , Wounds and Injuries/complications
17.
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
18.
Mo Med ; 118(1): 68-73, 2021.
Article in English | MEDLINE | ID: covidwho-1068428

ABSTRACT

Magnesium and vitamin D each have the possibility of affecting the immune system and consequently the cytokine storm and coagulation cascade in COVID-19 infections. Vitamin D is important for reducing the risk of upper respiratory tract infections and plays a role in pulmonary epithelial health. While the importance of vitamin D for a healthy immune system has been known for decades, the benefits of magnesium has only recently been elucidated. Indeed, magnesium is important for activating vitamin D and has a protective role against oxidative stress. Magnesium deficiency increases endothelial cell susceptibility to oxidative stress, promotes endothelial dysfunction, reduces fibrinolysis and increases coagulation. Furthermore, magnesium deficient animals and humans have depressed immune responses, which, when supplemented with magnesium, a partial or near full reversal of the immunodeficiency occurs. Moreover, intracellular free magnesium levels in natural killer cells and CD8 killer T cells regulates their cytotoxicity. Considering that magnesium and vitamin D are important for immune function and cellular resilience, a deficiency in either may contribute to cytokine storm in the novel coronavirus 2019 (COVID-19) infection.


Subject(s)
COVID-19/complications , Cytokine Release Syndrome/etiology , Disseminated Intravascular Coagulation/etiology , Immune System Diseases/etiology , Magnesium Deficiency/complications , Vitamin D Deficiency/complications , Animals , CD8-Positive T-Lymphocytes/drug effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Humans , Killer Cells, Natural/drug effects , Magnesium/administration & dosage , Magnesium/pharmacology , Magnesium/therapeutic use , Oxidative Stress/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Vitamin D/administration & dosage , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamins/administration & dosage , Vitamins/pharmacology , Vitamins/therapeutic use
19.
Int J Hematol ; 113(3): 320-329, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1064612

ABSTRACT

BACKGROUND: Disseminated intravascular coagulation (DIC) is noted in severe cases of coronavirus disease 2019 (COVID-19). Recently, a number of studies evaluating the diagnosis and treatment of DIC in COVID-19 patients have been reported. OBJECTIVE: The aim of this study is to identify existing gaps where further research is needed on the diagnosis and treatment of DIC complicated by COVID-19. METHODS: We used the PRISMA Extension for Scoping Reviews. MEDLINE, CENTRAL, WHO-ICTRP, ClinicalTrial.gov and PROSPERO were searched from their inception to 6 October 2020. RESULTS: Seven studies were selected; five were already published and two are ongoing. DIC was diagnosed using the International Society on Thrombosis and Hemostasis (ISTH) DIC score (n = 4) and the sepsis-induced coagulopathy (SIC) DIC score (n = 5). Seven studies examined the effectiveness of low molecular weight heparin (LMWH); of these, four studies used a prophylactic dose and five used a therapeutic dose of LMWH. A prophylactic dose of unfractionated heparin (UFH) was investigated in two studies. CONCLUSION: Studies on DIC diagnostic criteria and anticoagulants were limited to the ISTH or SIC scores and heparinoids, particularly LMWH. Further studies are needed to compare these with other available DIC scoring systems and anticoagulants.


Subject(s)
COVID-19/complications , COVID-19/virology , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/therapy , SARS-CoV-2 , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Blood Coagulation , Blood Coagulation Tests , Disease Management , Disease Susceptibility , Disseminated Intravascular Coagulation/blood , Humans , Prognosis , Treatment Outcome
20.
Int J Hematol ; 113(1): 45-57, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1064611

ABSTRACT

The pathology of coronavirus disease 2019 (COVID-19) is exacerbated by the progression of thrombosis, and disseminated intravascular coagulation (DIC), and cytokine storms. The most frequently reported coagulation/fibrinolytic abnormality in COVID-19 is the increase in D-dimer, and its relationship with prognosis has been discussed. However, limits exist to the utility of evaluation by D-dimer alone. In addition, since the coagulation/fibrinolytic condition sometimes fluctuates within a short period of time, regular examinations in recognition of the significance of the examination are desirable. The pathophysiology of disseminated intravascular coagulation (DIC) associated with COVID-19 is very different from that of septic DIC, and both thrombotic and hemorrhagic pathologies should be noted. COVID-19 thrombosis includes macro- and microthrombosis, with diagnosis of the latter depending on markers of coagulation and fibrinolysis. Treatment of COVID-19 is classified into antiviral treatment, cytokine storm treatment, and thrombosis treatment. Rather than providing uniform treatment, the treatment method most suitable for the severity and stage should be selected. Combination therapy with heparin and nafamostat is expected to develop in the future. Fibrinolytic therapy and adsorption therapy require further study.


Subject(s)
Blood Coagulation Disorders/etiology , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anticoagulants/therapeutic use , Benzamidines , Blood Coagulation Disorders/physiopathology , Blood Coagulation Tests , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinolysis , Guanidines/pharmacology , Guanidines/therapeutic use , Humans , Lymphopenia/etiology , Male , Middle Aged , Prognosis , Pulmonary Circulation , SARS-CoV-2/drug effects , Survivors , Thrombocytopenia/etiology , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombophilia/physiopathology
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