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1.
Clin Appl Thromb Hemost ; 27: 10760296211010973, 2021.
Article in English | MEDLINE | ID: covidwho-1582642

ABSTRACT

SARS-CoV-2 in COVID-19 triggers abnormalities in coagulation parameters that can contribute to thrombosis. The goals of this research were to determine the levels of fibrinogen, D-dimer and FDP in COVID-19 patients. Following a systematic study, among 1198 articles, 35 studies were included in the meta-analysis of fibrinogen levels in both severe and non-severe groups. The funnel plot, Egger's regression asymmetry test, and Begg's test used to measure the bias of publications. All meta-analysis performed by comprehensive meta-analysis version 2 (CMA2). The pooled findings of fibrinogen levels revealed a significant rise in fibrinogen levels in severe COVID-19 than non-severe patients with COVID-19. The D-dimer and FDP levels were significantly higher in severe patients than non-severe patients with COVID-19 were. The levels of fibrinogen, D-dimer, and FDP have increased significantly in ICU patients compared to non-ICU patients. Although, levels of clotting parameters do not always correlate with the severity of disease, these findings showed the diagnostic importance for fibrinogen, D-dimer, and FDP in COVID-19. The presence of a continuous rise in serial measurements of fibrinogen, D-dimer, and FDP may predict that patients with COVID-19 may become critically ill.


Subject(s)
COVID-19/blood , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Hemostasis , SARS-CoV-2 , Biomarkers , COVID-19/complications , Critical Illness , Humans , Prognosis , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/etiology
2.
Ann Med ; 53(1): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575822

ABSTRACT

INTRODUCTION: Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. MATERIALS AND METHODS: We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. RESULTS: Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. CONCLUSIONS: Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients. KEY MESSAGE Critically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended. Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases. An incidence of 7.6 cases per 1000 admission of IPHs was reported. Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.


Subject(s)
Anticoagulants/adverse effects , COVID-19/complications , Hematoma/epidemiology , Psoas Muscles/diagnostic imaging , Thrombophilia/drug therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Female , Glucocorticoids/therapeutic use , Hematoma/chemically induced , Hematoma/diagnosis , Hematoma/drug therapy , Heparin, Low-Molecular-Weight , Hospital Mortality , Humans , Incidence , Intensive Care Units , Italy/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Muscular Diseases , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Thrombophilia/etiology , Tomography, X-Ray Computed , Treatment Outcome
3.
Blood Coagul Fibrinolysis ; 32(8): 550-555, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1526212

ABSTRACT

Coronavirus-related disease-2019 (COVID-19)-associated coagulopathy presents predominantly with thrombosis and leads to complications in close association with inflammatory process. Soluble endothelial protein C receptor (sEPCR), which is the soluble form of EPCR, reduces the anticoagulant and anti-inflammatory activity of activated protein C. The purpose of this study is to investigate the relationship between sEPCR and the laboratory parameters and thorax computed tomography (CT) findings in the course of COVID-19. Twenty-five laboratory-confirmed [reverse transcription-quantitative polimerase chain reaction (RT-qPCR) positive] and 24 clinically diagnosed (RT-qPCR negative) COVID-19 patients were enrolled in the study. Blood specimens were collected for sEPCR and haematological and biochemical parameter measurement. Thorax CT was performed to detect COVID-19 findings. These parameters from RT-qPCR positive and negative patients were then compared. Although there was no difference between the groups in terms of symptoms, the time between the onset of symptoms and the admission time was shorter in RT-qPCR positive group (P = 0.000). sEPCR levels were significantly higher in the RT-qPCR positive group (P = 0.011). Patients with ground-glass opacity and bilateral involvement on thorax CT have higher serum sEPCR levels (P = 0.012 and 0.043, respectively). This study has shown for the first time that serum sEPCR levels, which is a member of coagulation cascade and has also been reported to be associated with inflammation, is higher in patients with positive RT-qPCR test and patients with GGO or bilateral involvement on thorax CT regardless of the PCR result.


Subject(s)
COVID-19/blood , Endothelial Protein C Receptor/blood , SARS-CoV-2 , Thrombophilia/blood , Adult , Aged , Aged, 80 and over , Biomarkers , Blood Glucose/analysis , Blood Proteins/analysis , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Solubility , Thrombophilia/etiology , Tomography, X-Ray Computed
4.
Blood Coagul Fibrinolysis ; 32(8): 544-549, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1526211

ABSTRACT

Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (P ≤ 0.003 for all). The presence of high TEG-6 s metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (P ≤ 0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.


Subject(s)
COVID-19/blood , SARS-CoV-2 , Thrombophilia/diagnosis , Adult , African Americans/statistics & numerical data , Aged , Aged, 80 and over , Biomarkers , COVID-19/complications , COVID-19/epidemiology , COVID-19 Testing , Cardiovascular Diseases/epidemiology , Comorbidity , Diabetes Mellitus/epidemiology , Early Diagnosis , Female , Fibrin/analysis , Fibrin Clot Lysis Time , Fibrinogen/analysis , Hospitalization , Humans , Hyperlipidemias/epidemiology , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Obesity/epidemiology , Organ Dysfunction Scores , Prognosis , Prospective Studies , Thrombelastography , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Treatment Outcome , /statistics & numerical data
5.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
6.
Clin Appl Thromb Hemost ; 27: 10760296211039288, 2021.
Article in English | MEDLINE | ID: covidwho-1448131

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a systemic disease that can be life-threatening involving immune and inflammatory responses, and that can result in potentially lethal complications, including venous thrombo-embolism (VTE). Forming an integrative approach to thrombo-prophylaxis and coagulation treatment for COVID-19 patients ensues. We aim at reviewing the literature for anticoagulation in the setting of COVID-19 infection to provide a summary on anticoagulation for this patient population. COVID-19 infection is associated with a state of continuous inflammation, which results in macrophage activation syndrome and an increased rate of thrombosis. Risk assessment models to predict the risk of thrombosis in critically ill patients have not yet been validated. Currently published guidelines suggest the use of prophylactic intensity over intermediate intensity or therapeutic intensity anticoagulant for patients with critical illness or acute illness related to COVID-19 infection. Critically ill COVID-19 patients who are diagnosed with acute VTE are considered to have a provoking factor, and, therefore, treatment duration should be at least 3 months. Patients with proximal deep venous thrombosis or pulmonary embolism should receive parenteral over oral anticoagulants with low-molecular-weight heparin or fondaparinux preferred over unfractionated heparin. In patients with impending hemodynamic compromise due to PE, and who are not at increased risk for bleeding, reperfusion may be necessary. Internists should remain updated on new emerging evidence regarding anticoagulation for COVID-19 patients. Awaiting these findings, we invite internists to perform individualized decisions that are unique for every patient and to base them on clinical judgment for risk assessment.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2 , Thrombophilia/drug therapy , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Consensus , Critical Illness , Disease Management , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/analysis , Fondaparinux/adverse effects , Fondaparinux/therapeutic use , Hemorrhage/chemically induced , Heparin/adverse effects , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/administration & dosage , Heparin, Low-Molecular-Weight/adverse effects , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Inpatients , Male , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Hematologic/prevention & control , Pregnancy Complications, Infectious/blood , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk , Thrombophilia/etiology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Venous Thrombosis/prevention & control
7.
Clin Appl Thromb Hemost ; 27: 10760296211045902, 2021.
Article in English | MEDLINE | ID: covidwho-1443743

ABSTRACT

INTRODUCTION: Diabetes is the most common of comorbidity in patients with SARS-COV-2 pneumonia. Coagulation abnormalities with D-dimer levels are increased in this disease. OBJECTIFS: We aimed to compare the levels of D-dimer in diabetic and non-diabetic patients with COVID 19. A link between D-dimer and mortality has also been established. MATERIALS: A retrospective study was carried out at the University Hospital Center of Oujda (Morocco) from November 01st to December 01st, 2020. Our study population was divided into two groups: a diabetic group and a second group without diabetes to compare clinical and biological characteristics between the two groups. In addition, the receiver operator characteristic curve was used to assess the optimal D-dimer cut-off point for predicting mortality in diabetics. RESULTS: 201 confirmed-COVID-19-patients were included in the final analysis. The median age was 64 (IQR 56-73), and 56% were male. Our study found that D-dimer levels were statistically higher in diabetic patients compared to non-diabetic patients. (1745 vs 845 respectively, P = 0001). D-dimer level > 2885 ng/mL was a significant predictor of mortality in diabetic patients with a sensitivity of 71,4% and a specificity of 70,7%. CONCLUSION: Our study found that diabetics with COVID-19 are likely to develop hypercoagulation with a poor prognosis.


Subject(s)
COVID-19/blood , Diabetes Mellitus/blood , Fibrin Fibrinogen Degradation Products/analysis , SARS-CoV-2 , Thrombophilia/blood , Aged , Area Under Curve , Biomarkers , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/epidemiology , Comorbidity , Diabetes Complications/blood , Diabetes Complications/epidemiology , Diabetes Mellitus/epidemiology , Female , Hospital Mortality , Humans , Hypertension/epidemiology , Inflammation/immunology , Kaplan-Meier Estimate , Male , Middle Aged , Oxidative Stress , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Thrombophilia/etiology , Thrombophilia/immunology
8.
Folia Morphol (Warsz) ; 80(3): 714-717, 2021.
Article in English | MEDLINE | ID: covidwho-1399547

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a condition caused by a novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease's course ranges from entirely asymptomatic to severely ill patients. Hypercoagulation is often a complication of this disease, worsening the prognosis, which is extremely important in patients at higher risk of thromboembolic events, such as atrial fibrillation (AF), where thrombus formation in the left atrial appendage (LAA) is frequent. LAA could be of various sizes, volumes, and shapes, distinguish several morphologies, from which the WindSock LAA is the most frequent. In contrast, thromboembolic complications occur most frequently in patients with AF and the Cactus LAA. We present a clinical case of a 70-year-old woman with an initial negative real-time polymerase chain reaction (RT-PCR) test for SARS-CoV-2, suspicion of device-related infection after dual pacemaker implantation, AF, and LAA without thrombus in the initial transoesophageal echocardiography (TEE). Despite apixaban treatment, spontaneous restoration of sinus rhythm, and WindSock LAA morphology, the sludge in LAA was diagnosed in control TEE. The patient did not present any typical clinical COVID-19 symptoms but re-checked the RT-PCR test for SARS-CoV-2 infection was positive. The described case presents echocardiographic evidence of hypercoagulation as the first and only feature of SARS-CoV-2 condition besides the usual morphological presentation of the WindSock LAA.


Subject(s)
Atrial Appendage , Atrial Fibrillation , COVID-19 , Echocardiography , Thrombophilia , Aged , Atrial Appendage/diagnostic imaging , COVID-19/diagnosis , Female , Humans , SARS-CoV-2 , Thrombophilia/etiology
9.
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
10.
Rev Mal Respir ; 37(6): 505-510, 2020 Jun.
Article in French | MEDLINE | ID: covidwho-1386577

ABSTRACT

The French-language Respiratory Medicine Society (SPLF) proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: (1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea; (2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit; (3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome…). These proposals may evolve over time as more knowledge becomes available.


Subject(s)
Aftercare/methods , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Aftercare/standards , Ambulatory Care/methods , Ambulatory Care/standards , COVID-19 , Cardiovascular Diseases/prevention & control , Coronavirus Infections/complications , Coronavirus Infections/rehabilitation , Critical Care/methods , Critical Care/standards , Diagnostic Techniques, Respiratory System/standards , Disease Management , Emergency Medical Services/methods , Emergency Medical Services/standards , Health Priorities , Hospitalization , Humans , Inpatients , Outpatients , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/rehabilitation , Respiratory Therapy/methods , Respiratory Therapy/standards , Symptom Assessment/methods , Symptom Assessment/standards , Thromboembolism/prevention & control , Thrombophilia/drug therapy , Thrombophilia/etiology
11.
Adv Med Sci ; 66(2): 372-380, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1379020

ABSTRACT

OBJECTIVES: D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. METHODS: A literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). RESULTS: Thirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 â€‹% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 â€‹% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 â€‹% confidence interval, CI 0.42 to 0.77; p â€‹< â€‹0.001). There was extreme between-study heterogeneity (I2 â€‹= â€‹90.2 â€‹%; p â€‹< â€‹0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p â€‹= â€‹0.048) and D-dimer (p â€‹= â€‹0.001). CONCLUSIONS: Prolonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , International Normalized Ratio , Thrombophilia , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Humans , International Normalized Ratio/methods , International Normalized Ratio/statistics & numerical data , Mortality , SARS-CoV-2 , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/etiology
13.
Blood Coagul Fibrinolysis ; 32(8): 550-555, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1331612

ABSTRACT

Coronavirus-related disease-2019 (COVID-19)-associated coagulopathy presents predominantly with thrombosis and leads to complications in close association with inflammatory process. Soluble endothelial protein C receptor (sEPCR), which is the soluble form of EPCR, reduces the anticoagulant and anti-inflammatory activity of activated protein C. The purpose of this study is to investigate the relationship between sEPCR and the laboratory parameters and thorax computed tomography (CT) findings in the course of COVID-19. Twenty-five laboratory-confirmed [reverse transcription-quantitative polimerase chain reaction (RT-qPCR) positive] and 24 clinically diagnosed (RT-qPCR negative) COVID-19 patients were enrolled in the study. Blood specimens were collected for sEPCR and haematological and biochemical parameter measurement. Thorax CT was performed to detect COVID-19 findings. These parameters from RT-qPCR positive and negative patients were then compared. Although there was no difference between the groups in terms of symptoms, the time between the onset of symptoms and the admission time was shorter in RT-qPCR positive group (P = 0.000). sEPCR levels were significantly higher in the RT-qPCR positive group (P = 0.011). Patients with ground-glass opacity and bilateral involvement on thorax CT have higher serum sEPCR levels (P = 0.012 and 0.043, respectively). This study has shown for the first time that serum sEPCR levels, which is a member of coagulation cascade and has also been reported to be associated with inflammation, is higher in patients with positive RT-qPCR test and patients with GGO or bilateral involvement on thorax CT regardless of the PCR result.


Subject(s)
COVID-19/blood , Endothelial Protein C Receptor/blood , SARS-CoV-2 , Thrombophilia/blood , Adult , Aged , Aged, 80 and over , Biomarkers , Blood Glucose/analysis , Blood Proteins/analysis , COVID-19/complications , COVID-19/diagnostic imaging , Female , Humans , Lung/diagnostic imaging , Male , Middle Aged , Solubility , Thrombophilia/etiology , Tomography, X-Ray Computed
14.
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
15.
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
16.
Shock ; 55(3): 316-320, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1304005

ABSTRACT

ABSTRACT: The coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our institution, many critically ill COVID-19-positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, Mass) in patients admitted to the intensive care unit over a period of 3 weeks. In 25 patients who had a ROTEM test, we found that 11 (44%) met criteria for fibrinolysis shutdown. Eight of 9 (73%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.


Subject(s)
COVID-19/complications , Fibrinolysis , Intensive Care Units , Thrombelastography , Thrombophilia/diagnosis , Thrombosis/diagnosis , Venous Thromboembolism/diagnosis , Adult , Aged , COVID-19/blood , COVID-19/diagnosis , Clinical Decision-Making , Female , Fibrinolysis/drug effects , Fibrinolytic Agents/therapeutic use , Humans , Male , Middle Aged , Patient Selection , Predictive Value of Tests , Retrospective Studies , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/blood , Thrombosis/drug therapy , Thrombosis/etiology , Venous Thromboembolism/blood , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
17.
Curr Opin Hematol ; 28(5): 339-344, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1294830

ABSTRACT

PURPOSE OF REVIEW: Protein S (PS) is an essential natural anticoagulant. PS deficiency is a major contributor to acquired hypercoagulability. Acquired hypercoagulability causes myocardial infarction, stroke, and deep vein thrombosis in millions of individuals. Yet, despite its importance in hemostasis, PS is the least understood anticoagulant. Even after 40 years since PS was first described, we are still uncovering information about how PS functions. The purpose of this review is to highlight recent findings that advance our understanding of the functions of PS and explain hypercoagulability caused by severe PS deficiency. RECENT FINDINGS: PS has long been described as a cofactor for Activated Protein C (APC) and Tissue Factor Pathway Inhibitor (TFPI). However, a recent report describes direct inhibition of Factor IXa (FIXa) by PS, an activity of PS that had been completely overlooked. Thrombophilia is becoming a more frequently reported disorder. Hereditary PS deficiency is an anticoagulant deficiency that results eventually in thrombophilia. In addition, PS deficiency is a predisposing factor for venous thromboembolism (VTE), but an effect of PS deficiency in arterial thrombosis, such as arterial ischemic stroke, is uncertain. Plasma PS concentration decreases in pregnant women. Inherited thrombophilias are important etiologies for recurrent pregnancy loss, and anticoagulation therapy is of benefit to women with recurrent pregnancy loss who had documented only PS deficiency.Hypoxia is a risk factor for VTE, and hypoxia downregulates plasma PS level. Importantly, COVID-19 can lead to hypoxemia because of lung damage from IL6-driven inflammatory responses to the viral infection. Because hypoxia decreases the abundance of the key anticoagulant PS, we surmise that the IL6-induced cytokine explosion combined with hypoxemia causes a drop in PS level that exacerbates the thrombotic risk in COVID-19 patients. SUMMARY: This review is intended to advance understanding of the anticoagulant function of an important plasma protein, PS. Despite 40+ years of research, we have not had a complete description of PS biology as it pertains to control of blood coagulation. However, the picture of PS function has become sharper with the recent discovery of FIXa inhibition by PS. Hemostasis mediated by PS now includes regulation of FIXa activity alongside the cofactor activities of PS in the TFPI/APC pathways. In addition, the direct inhibition of FIXa by PS suggests that PS, particularly a small derivative of PS, could be used to treat individuals with PS deficiencies or abnormalities that cause thrombotic complications.


Subject(s)
COVID-19/complications , Hemostasis , Protein S/metabolism , SARS-CoV-2/isolation & purification , Thrombophilia/pathology , COVID-19/metabolism , COVID-19/virology , Humans , Thrombophilia/etiology , Thrombophilia/metabolism
18.
Curr Res Transl Med ; 69(4): 103300, 2021 10.
Article in English | MEDLINE | ID: covidwho-1294187

ABSTRACT

Heparin has served as a mainstream anticoagulant for over eight decades. Clinically heparin-derived compounds significantly contribute to prevention and treatment of thrombotic events complicated in numerous medical conditions such as venous thromboembolism, coronary artery disease and extracorporeal circulation processes. Moreover in recent years, various off-labeled efficacious potentials of heparin beyond anti-coagulation are dramatically emerging, and increasingly investigated in clinical studies. Herein this article presents a comprehensive update on the expanded applications of heparin agents, covering the pregnant clinic, respiratory inflammation, renal disease, sepsis, pancreatitis, among others. It aims to maximize the beneficial profile of a pharmaceutical product through medical re-purposing development, exemplified by heparin, to address the unmet clinical needs of severe illness including coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Heparin/therapeutic use , SARS-CoV-2 , Abortion, Habitual/prevention & control , Burns/drug therapy , COVID-19/blood , COVID-19/complications , Female , Forecasting , Heparin/pharmacology , Humans , Neoplasms/blood , Neoplasms/complications , Nephrotic Syndrome/drug therapy , Pancreatitis/drug therapy , Pregnancy , Pregnancy Complications/drug therapy , Respiration Disorders/drug therapy , Sepsis/drug therapy , Thromboembolism/prevention & control , Thrombophilia/drug therapy , Thrombophilia/etiology
19.
Clin Appl Thromb Hemost ; 27: 10760296211027653, 2021.
Article in English | MEDLINE | ID: covidwho-1286792

ABSTRACT

Identifying a hypercoagulable state in patients with COVID-19 may help identify those at risk for virus-induced thromboembolic events and improve clinical outcomes using personalized therapeutic approaches. Herein, we aimed to perform a global assessment of the patients' hemostatic system with COVID-19 using rotational thromboelastometry (ROTEM) and to describe whether patients with different disease severities present different coagulation profiles. Together with 37 healthy volunteers, a total of 65 patients were included and then classified as having mild, moderate, and severe disease depending on clinical severity. Peripheral blood samples were collected and analyzed using a ROTEM Coagulation Analyzer. Also, complete blood count and coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels were measured at admission. EXTEM and INTEM MCF (P < 0.001) values were significantly higher and the EXTEM CFT (P = 0.002) value was significantly lower in patients with COVID-19 when compared with controls. In particular, patients with the severe disease showed a significant decrease in CFT (P < 0.001) and an increase in MCF (P < 0.001) in both INTEM and EXTEM assays compared with patients with the non-severe disease. Correlation analysis revealed significant correlations between ROTEM parameters and other coagulation parameters. There were significant positive correlations between fibrinogen, D-dimer, platelet count, and MCF in both EXTEM and INTEM assays. Our data demonstrate thromboelastographic signs of hypercoagulability in patients with COVID-19, which is more pronounced in patients with increased disease severity. Therefore, ROTEM analysis can classify subsets of patients with COVID-19 at significant thrombotic risk and assist in clinical decisions.


Subject(s)
COVID-19/blood , SARS-CoV-2 , Thrombelastography , Thrombophilia/etiology , Adult , Blood Cell Count , Blood Coagulation Tests , Blood Proteins/analysis , Case-Control Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/diagnosis
20.
Thromb Res ; 205: 24-28, 2021 09.
Article in English | MEDLINE | ID: covidwho-1284573

ABSTRACT

BACKGROUND: It is still unknown whether COVID-19 vaccines induce a prothrombotic state or increase the hypercoagulable condition in subjects with a predisposition to thrombosis. OBJECTIVES: We evaluated the coagulation profile in a series of healthy subjects who received the first dose of the BNT162b2 or the ChAdOx1 vaccines and assessed whether hypercoagulability developed. PATIENTS/METHODS: Volunteers among the staff of the University of Padua or health care professionals in the Padua University Hospital who had received either the ChAdOx1 or BNT162b2 vaccine in the previous 10 ± 2 days were eligible. A cohort of unvaccinated volunteers among family members of the University staff acted as control group. Global coagulation monitoring was assessed by whole blood rotational thromboelastometry, whole blood impedance aggregometry and thrombin generation. Platelet count was also obtained. RESULTS: One hundred and ninety subjects were enrolled: 101 (53.2%) received the ChAdOx1 vaccine and 89 (46.8%) the BNT162b2 vaccine. Twenty-eight non-vaccinated subjects acted as controls. Thromboelastometry parameters were all comparable among groups. Thrombin receptor activating peptide (TRAP)-, ADP- and ASPI-induced platelet aggregation were similar among groups, as well as platelet count. Endogenous thrombin potential (ETP) was comparable among groups. The results were confirmed after controlling for age, gender and hormonal. Considering women taking combined oral contraceptives or thrombophilia carriers, no differences were detected in thromboelastometry or thrombin generation parameters between subjects who received ChAdOx1 vs. BNT162b2 vaccines. CONCLUSIONS: No significant activation of fibrinogen-driven coagulation, plasma thrombin generation or clinically meaningful platelet aggregation after ChAdOx1 or BNT162b2 vaccination was observed.


Subject(s)
COVID-19 , Thrombophilia , COVID-19 Vaccines , Female , Humans , Pilot Projects , SARS-CoV-2 , Thrombophilia/etiology , Vaccination
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