Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 99
Filter
Add filters

Document Type
Year range
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.
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
3.
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
4.
Sci Rep ; 11(1): 21888, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1506965

ABSTRACT

Hypercoagulability and the need for prioritizing coagulation markers for prognostic abilities have been highlighted in COVID-19. We aimed to quantify the associations of D-dimer with disease progression in patients with COVID-19. This systematic review and meta-analysis was registered with PROSPERO, CRD42020186661.We included 113 studies in our systematic review, of which 100 records (n = 38,310) with D-dimer data) were considered for meta-analysis. Across 68 unadjusted (n = 26,960) and 39 adjusted studies (n = 15,653) reporting initial D-dimer, a significant association was found in patients with higher D-dimer for the risk of overall disease progression (unadjusted odds ratio (uOR) 3.15; adjusted odds ratio (aOR) 1.64). The time-to-event outcomes were pooled across 19 unadjusted (n = 9743) and 21 adjusted studies (n = 13,287); a strong association was found in patients with higher D-dimers for the risk of overall disease progression (unadjusted hazard ratio (uHR) 1.41; adjusted hazard ratio (aHR) 1.10). The prognostic use of higher D-dimer was found to be promising for predicting overall disease progression (studies 68, area under curve 0.75) in COVID-19. Our study showed that higher D-dimer levels provide prognostic information useful for clinicians to early assess COVID-19 patients at risk for disease progression and mortality outcomes. This study, recommends rapid assessment of D-dimer for predicting adverse outcomes in COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/immunology , Fibrin Fibrinogen Degradation Products/chemistry , Adult , Aged , Area Under Curve , Biomarkers/blood , COVID-19/epidemiology , Disease Progression , Female , Humans , Male , Middle Aged , Odds Ratio , Prognosis , Proportional Hazards Models , Respiration, Artificial , Risk , SARS-CoV-2 , Severity of Illness Index , Thrombophilia/blood
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: 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
7.
Pediatr Blood Cancer ; 68(12): e29355, 2021 12.
Article in English | MEDLINE | ID: covidwho-1414402

ABSTRACT

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p < .01), increased alpha angle (75.0° vs. 65.7°, p < .01), increased maximum amplitude (70.8 vs. 58.3 mm, p < .01), and decreased lysis in 30 minutes (Ly30) (1.1% vs. 3.7%, p = .03); consistent with increased clot formation rate and strength, and reduced fibrinolysis. TEG maximum amplitude was moderately correlated with erythrocyte sedimentation rate (ESR) (r = 0.60, p = .02), initial platelet count (r = 0.67, p < .01), and peak platelet count (r = 0.51, p = .03). TEG alpha angle was moderately correlated with peak platelet count (r = 0.54, p = .02). Seventeen (57%) patients received aspirin (ASA) and anticoagulation, five (17%) received only ASA, and three (10%) received only anticoagulation. No patients had a symptomatic thrombotic event. Six (20%) patients had a bleeding event, none of which was major. CONCLUSIONS: Patients with MIS-C had evidence of hypercoagulability on TEG. Increased ESR and platelets were associated with higher clot strength. Patients were prophylactically treated with ASA or anticoagulation with no symptomatic thrombosis or major bleeding. Further multicenter study is required to characterize the rate of thrombosis and optimal thromboprophylaxis algorithm in this patient population.


Subject(s)
Blood Coagulation , COVID-19/complications , Systemic Inflammatory Response Syndrome/blood , Thrombophilia/blood , Adolescent , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Blood Coagulation/drug effects , Blood Platelets/drug effects , COVID-19/blood , COVID-19/drug therapy , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies , Systemic Inflammatory Response Syndrome/drug therapy , Thrombelastography , Thrombophilia/drug therapy
8.
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
9.
J Am Acad Dermatol ; 85(2): 301-310, 2021 08.
Article in English | MEDLINE | ID: covidwho-1379127

ABSTRACT

The skin often provides initial clues of hypercoagulability with features such as livedo reticularis, livedo racemosa, retiform purpura, necrosis, and ulcerations. Because these cutaneous manifestations are nonspecific, laboratory testing is often needed to evaluate for underlying causes of hypercoagulability. Importantly, these disorders are reported to be the most common mimicker, resulting in an erroneous diagnosis of pyoderma gangrenosum. Understanding inherent properties of, and indications for, available tests is necessary for appropriate ordering and interpretation of results. Additionally, ordering of these tests in an indiscriminate manner may lead to inaccurate results, complicating the interpretation and approach to management. This second article in this continuing medical education series summarizes information on methodology, test characteristics, and limitations of several in vitro laboratory tests used for the work up of hypercoagulability and vasculopathic disease as it pertains to dermatologic disease.


Subject(s)
Skin Diseases/blood , Skin Diseases/diagnosis , Thrombophilia/blood , Thrombophilia/diagnosis , Clinical Laboratory Techniques , Humans , Skin Diseases/etiology , Thrombophilia/complications
10.
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
11.
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
12.
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
13.
Pharmacol Res ; 158: 104950, 2020 08.
Article in English | MEDLINE | ID: covidwho-1318942

ABSTRACT

Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 µg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 µg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes' function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Hypoxia/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Thrombophilia/drug therapy , Aged , Aspirin/therapeutic use , COVID-19 , Clopidogrel/therapeutic use , Compassionate Use Trials , Coronavirus Infections/complications , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypoxia/complications , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Proof of Concept Study , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/complications , Tirofiban/therapeutic use
14.
J Thromb Haemost ; 18(7): 1738-1742, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317984

ABSTRACT

BACKGROUND: The severe inflammatory state secondary to COVID-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer, as well as low fibrinogen. AIMS: Whole blood from 24 patients admitted at the intensive care unit because of COVID-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. RESULTS: TEG parameters are consistent with a state of hypercoagulability as shown by decreased values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n = 11) were increased. Antithrombin (n = 11) was marginally decreased and protein C (n = 11) was increased. CONCLUSION: The results of this cohort of patients with COVID-19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage, and optimal duration of prophylaxis.


Subject(s)
Betacoronavirus/pathogenicity , Blood Coagulation , Coronavirus Infections/diagnosis , Intensive Care Units , Pneumonia, Viral/diagnosis , Thrombelastography , Thrombophilia/diagnosis , Adult , Aged , Biomarkers/blood , COVID-19 , Case-Control Studies , Coronavirus Infections/blood , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Inflammation Mediators/blood , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Predictive Value of Tests , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/virology , Young Adult
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.
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
18.
Hemoglobin ; 45(2): 124-128, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1281786

ABSTRACT

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(-) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (-) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient's risk of death assessment.


Subject(s)
COVID-19/blood , Diabetes Mellitus/blood , Glycated Hemoglobin A/analysis , Hyperglycemia/blood , SARS-CoV-2 , Adult , Aged , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , Critical Care/statistics & numerical data , Diabetes Complications/blood , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Hyperglycemia/etiology , L-Lactate Dehydrogenase/blood , Leukocyte Count , Male , Middle Aged , Neutrophils , Oxygen/blood , Partial Pressure , Procalcitonin/blood , Prognosis , Risk , Severity of Illness Index , Thrombophilia/blood , Thrombophilia/etiology
19.
Clin Appl Thromb Hemost ; 27: 10760296211021495, 2021.
Article in English | MEDLINE | ID: covidwho-1277870

ABSTRACT

The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, P < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.


Subject(s)
Anticoagulants/pharmacology , Bleeding Time , Blood Coagulation/drug effects , COVID-19/blood , Hemorrhage/chemically induced , International Normalized Ratio , Pandemics , SARS-CoV-2 , Thrombophilia/blood , Warfarin/pharmacology , Aged , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , COVID-19/complications , Dose-Response Relationship, Drug , Female , Heart Valve Prosthesis/adverse effects , Hemorrhage/psychology , Humans , Hypertension/complications , Male , Medication Adherence , Middle Aged , Patient Acceptance of Health Care , Pulmonary Embolism/drug therapy , Retrospective Studies , Self Medication , Thrombophilia/drug therapy , Thrombophilia/etiology , Warfarin/administration & dosage , Warfarin/adverse effects , Warfarin/therapeutic use
20.
Blood ; 138(4): 344-349, 2021 07 29.
Article in English | MEDLINE | ID: covidwho-1255893

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with the hypercoagulable state. Tissue factor (TF) is the primary cellular initiator of coagulation. Most of the TF expressed on cell surfaces remains cryptic. Sphingomyelin (SM) is responsible for maintaining TF in the encrypted state, and hydrolysis of SM by acid sphingomyelinase (ASMase) increases TF activity. ASMase was shown to play a role in virus infection biology. In the present study, we investigated the role of ASMase in SARS-CoV-2 infection-induced TF procoagulant activity. Infection of human monocyte-derived macrophages (MDMs) with SARS-CoV-2 spike protein pseudovirus (SARS-CoV-2-SP-PV) markedly increased TF procoagulant activity at the cell surface and released TF+ extracellular vesicles. The pseudovirus infection did not increase either TF protein expression or phosphatidylserine externalization. SARS-CoV-2-SP-PV infection induced the translocation of ASMase to the outer leaflet of the plasma membrane, which led to the hydrolysis of SM in the membrane. Pharmacologic inhibitors or genetic silencing of ASMase attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Inhibition of the SARS-CoV-2 receptor, angiotensin-converting enzyme-2, attenuated SARS-CoV-2-SP-PV-induced increased TF activity. Overall, our data suggest that SARS-CoV-2 infection activates the coagulation by decrypting TF through activation of ASMase. Our data suggest that the US Food and Drug Administration-approved functional inhibitors of ASMase may help treat hypercoagulability in patients with COVID-19.


Subject(s)
COVID-19/blood , Macrophages/virology , Membrane Proteins/physiology , SARS-CoV-2 , Sphingomyelin Phosphodiesterase/physiology , Spike Glycoprotein, Coronavirus/physiology , Thrombophilia/etiology , Thromboplastin/physiology , Angiotensin-Converting Enzyme 2/physiology , COVID-19/complications , Cell-Derived Microparticles , Enzyme Activation , Humans , Hydrolysis , Macrophages/enzymology , Molecular Targeted Therapy , Plasmids , Protein Transport , RNA Interference , RNA, Small Interfering/genetics , Receptors, Virus/physiology , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Sphingomyelins/physiology , Thrombophilia/blood , Thrombophilia/drug therapy , Thrombophilia/enzymology
SELECTION OF CITATIONS
SEARCH DETAIL
...