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1.
Clin Appl Thromb Hemost ; 28: 10760296221117997, 2022.
Article in English | MEDLINE | ID: covidwho-1986656

ABSTRACT

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.


Subject(s)
COVID-19 , Pulmonary Embolism , Adult , COVID-19/complications , COVID-19/diagnosis , Emergency Service, Hospital , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Predictive Value of Tests , Pulmonary Embolism/diagnosis , Pulmonary Embolism/epidemiology , Retrospective Studies , Sensitivity and Specificity
2.
Atherosclerosis ; 357: 33-40, 2022 09.
Article in English | MEDLINE | ID: covidwho-1966356

ABSTRACT

BACKGROUND AND AIMS: High levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge. METHODS: We studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination. Thrombotic activity was marked by elevated D-dimer while inflammation was marked by elevated interleukin-6, C-reactive protein, and procalcitonin. Patients were followed until death (N = 36) or discharge (N = 175). RESULTS: A 2-fold higher D-dimer was associated with 14% (95%CI: 8.1-20%) higher lipoprotein(a). Conversely, 2-fold higher interleukin-6, C-reactive protein, and procalcitonin were associated with respectively 4.3% (0.62-7.8%), 5.7% (0.15-5.2%), and 8.7% (5.2-12%) lower lipoprotein(a). For hospital death, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 1.26 (95%CI:0.91-1.73). Corresponding hazard ratios per 2-fold higher biomarker were 0.93 (0.75-1.16) for D-dimer, 1.42 (1.17-1.73) for interleukin-6, 1.44 (0.95-2.17) for C-reactive protein, and 1.44 (1.20-1.73) for procalcitonin. For hospital discharge, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 0.91 (95%CI:0.79-1.06). Corresponding hazard ratios per 2-fold higher biomarker were 0.86 (0.75-0.98) for D-dimer, 0.84 (0.76-0.92) for interleukin-6, 0.80 (0.71-0.90) for C-reactive protein, and 0.76 (0.67-0.88) for procalcitonin. CONCLUSIONS: In COVID-19 patients, thrombotic activity marked by elevated D-dimer was associated with higher lipoprotein(a) while elevated inflammatory biomarkers of interleukin-6, C-reactive protein, and procalcitonin were associated with lower lipoprotein(a); however, elevated lipoprotein(a) was not associated with rate of hospital death or discharge.


Subject(s)
COVID-19 , Thrombosis , Biomarkers , C-Reactive Protein/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Inflammation , Interleukin-6 , Lipoprotein(a) , Procalcitonin , Retrospective Studies , SARS-CoV-2
3.
Saudi Med J ; 43(7): 723-729, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1934738

ABSTRACT

OBJECTIVES: To examine D-dimer, coagulation profile, and platelet count among patients hospitalized with coronavirus disease-19 (COVID-19) and compare them to findings from non-COVID-19 subjects. METHODS: The participants in this retrospective hospital-based observational study design included 112 confirmed diagnosed with COVID-19 who were admitted to King Khaled Hospital, Najran, Saudi Arabia, and another 112 non-COVID-19 subjects as a comparative group. Laboratory investigations, demographic and clinical records were obtained from participants' electronic indexed medical records. Coronavirus disease-19 diagnosis was confirmed according to positive real time polymerase chain reaction assay carried out at the hospital's central laboratory, where samples were extracted from a nasopharyngeal swab. Pneumonia related to COVID-19 is classified as critical, severe, moderate, mild, and asymptomatic whereas thrombocytopenia was marked when the platelet count was <150.00×109/L. Suitable statistical analysis was applied to determine possible differences between the findings from the 2 groups. RESULTS: The D-dimer and activated partial thromboplastin clotting time mean values were significantly elevated (p<0.001). The international normalized ratio and platelet count mean values confirmed a significant decrease (p<0.001). Thrombocytopenia was found 9 times in COVID-19 higher than in the non-COVID-19. D-dimer and prothrombin time mean values increased significantly among the COVID-19 patients with all patterns of symptoms on admission (p<0.001). CONCLUSION: D-dimer mean values increased significantly in deceased COVID-19 and in hospitalized intensive care unit (ICU) wards patients (p<0.001), indicating a potential predictive and prognostic severity marker, particularly among COVID-19 patients in the ICU.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products , Thrombocytopenia , COVID-19/blood , COVID-19/diagnosis , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Prognosis , Retrospective Studies , Thrombocytopenia/blood , Thrombocytopenia/virology
4.
Semin Thromb Hemost ; 48(6): 672-679, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1931536

ABSTRACT

D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mammary and salivary glands, which ensures smooth flow of arising fluids where any blood contamination could be immediately lysed. In addition, healthy individuals can also regularly sustain minor injuries, often unbeknown to them, and wound healing follows clot formation in these situations. D-dimers can also arise in anxiety and following exercise, and are also markers of inflammation. Lung inflammation (triggered by microbes or foreign particles) is perhaps also particularly relevant, since the hemostasis system and fibrinolysis help to trap and remove such debris. Lung inflammation in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to D-dimer levels additive to thrombosis in patients with COVID-19 (coronavirus disease 2019). Indeed, severe COVID-19 can lead to multiple activation events, including inflammation, primary and secondary hemostasis, and fibrinolysis, all of which may contribute to cumulative D-dimer development. Finally, D-dimer testing has also found a role in the diagnosis and triaging of the so-called (COVID-19) vaccine-induced thrombotic thrombocytopenia.


Subject(s)
COVID-19 , Disseminated Intravascular Coagulation , Thromboembolism , Thrombosis , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/etiology , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Inflammation , SARS-CoV-2
5.
Exp Biol Med (Maywood) ; 247(17): 1570-1576, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1896295

ABSTRACT

D-dimer is an established biomarker of thromboembolism and severity in COVID-19. We and others have recently reported the dysregulation of tissue factor pathway inhibitor (TFPI), FXIII, fibrinolytic pathway, inflammatory markers, and tissue injury markers, particularly in severe COVID-19. However, association of these markers with thromboembolism in COVID-19 remains elusive. The correlation analyses between these markers in patients with moderate (non-ICU) and severe COVID-19 (ICU) were performed to delineate the potential pathomechanisms and impact of thromboembolism. We observe a negative correlation of plasma TFPI (r2 = 0.148, P = 0.035), FXIII (r2 = 0.242, P = 0.006), and plasminogen (r2 = 0.27, P = 0.003) with D-dimer, a biomarker of thromboembolism, levels in these patients. Further analysis revealed a strong positive correlation between fibrinolytic markers tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) (r2 = 0.584, P < 0.0001). Interestingly, a significant positive correlation of PAI-1, but not tPA, was observed with platelets and endothelial cells dysfunction markers P-selectin (r2 = 0.184, P = 0.01) and soluble CD40 ligand (sCD40 L) (r2 = 0.163, P = 0.02). Moreover, calprotectin (S100A8/A9) and cystatin C (CST3), previously linked with thromboembolism, exhibited positive correlations with each other (r2 = 0.339, P = 0.0007) and with the level of D-dimer independently in COVID-19. Finally, the tissue injury marker myoglobin demonstrated a strong positive correlation with D-dimer (r2 = 0.408, P = 0.0001). Taken together, inverse correlations of TFPI and FXIII with D-dimer suggest the TF pathway activation and aberrant fibrin polymerization in COVID-19 patients. The elevated level of PAI-1 is potentially contributed by activated platelets and endothelial cells. S100A8/A9 may also play roles in impaired fibrinolysis and thromboembolism, in part, through regulating the CST3. These findings strengthen the understanding of thromboembolism and tissue injury and may help in better management of thromboembolic complications in COVID-19 patients.


Subject(s)
COVID-19 , Thromboembolism , Biomarkers , CD40 Ligand/metabolism , Cystatin C/metabolism , Endothelial Cells/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysis/physiology , Humans , Leukocyte L1 Antigen Complex , Lipoproteins , Myoglobin/metabolism , P-Selectin/metabolism , Plasminogen/metabolism , Plasminogen Activator Inhibitor 1 , Tissue Plasminogen Activator/metabolism
6.
Oxid Med Cell Longev ; 2022: 8997709, 2022.
Article in English | MEDLINE | ID: covidwho-1807711

ABSTRACT

INTRODUCTION: Health care workers have had a challenging task since the COVID-19 outbreak. Prompt and effective predictors of clinical outcomes are crucial to recognize potentially critically ill patients and improve the management of COVID-19 patients. The aim of this study was to identify potential predictors of clinical outcomes in critically ill COVID-19 patients. METHODS: The study was designed as a retrospective cohort study, which included 318 patients treated from June 2020 to January 2021 in the Intensive Care Unit (ICU) of the Clinical Hospital Center "Bezanijska Kosa" in Belgrade, Serbia. The verified diagnosis of COVID-19 disease, patients over 18 years of age, and the hospitalization in ICU were the criteria for inclusion in the study. The optimal cutoff value of D-dimer, CRP, IL-6, and PCT for predicting hospital mortality was determined using the ROC curve, while the Kaplan-Meier method and log-rank test were used to assess survival. RESULTS: The study included 318 patients: 219 (68.9%) were male and 99 (31.1%) female. The median age of patients was 69 (60-77) years. During the treatment, 195 (61.3%) patients died, thereof 130 male (66.7%) and 65 female (33.3%). 123 (38.7%) patients were discharged from hospital treatment. The cutoff value of IL-6 for in-hospital death prediction was 74.98 pg/mL (Sn 69.7%, Sp 62.7%); cutoff value of CRP was 81 mg/L (Sn 60.7%, Sp 60%); cutoff value of procalcitonin was 0.56 ng/mL (Sn 81.1%, Sp 76%); and cutoff value of D-dimer was 760 ng/mL FEU (Sn 63.4%, Sp 57.1%). IL-6 ≥ 74.98 pg/mL, CRP ≥ 81 mg/L, PCT ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL were statistically significant predictors of in-hospital mortality. CONCLUSION: IL-6 ≥ 74.98 pg/mL, CRP values ≥ 81 mg/L, procalcitonin ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL could effectively predict in-hospital mortality in COVID-19 patients.


Subject(s)
C-Reactive Protein/metabolism , COVID-19 , Fibrin Fibrinogen Degradation Products/metabolism , Hospital Mortality , Intensive Care Units , Interleukin-6/blood , Patient Admission , SARS-CoV-2/metabolism , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/therapy , Female , Humans , Male , Middle Aged , Retrospective Studies
7.
JNMA J Nepal Med Assoc ; 60(247): 259-262, 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1754237

ABSTRACT

Introduction: Serum D-dimer is a protein fragment generated during the final phase of clot formation. Increased serum D-dimer levels indicate the hemostatic change in patients, likely related to the prothrombotic switch. As the world is battling with the damaging effect of coronavirus disease, it is very important to find out the early and effective predictors of prognosis to improve the management of COVID-19 patients. Thus, our study aims to find out the prevalence of increased D-dimer levels in coronavirus disease patients. Methods: A descriptive cross-sectional study was conducted on a total of 235 patients admitted in the COVID ward and COVID Intensive Care Units at a tertiary care hospital from July 2020 to August 2021 after getting ethical approval (Reference number: 401/2020) from the Institutional Review Committee. A convenience sampling method was used for sample collection. The highest recorded values for D-dimer during the hospital stay were taken for data collection. The data were entered in Microsoft Excel 2013 and analyzed using Statistical Package for the Social Sciences version 16.0. Point estimate at 95% Confidence Interval was calculated along with frequency, proportion, mean and standard deviation. Results: Among 235 patients, elevated D- dimer level was in 175 (74.46%) (68.88-80.04 at 95% Confidence Interval). Majority of the patients were males 136 (77.71%) whereas 39 (22.28%) of the patients were females. Conclusions: The prevalence of raised D-dimer levels was quite higher in our studies compared to other studies done in different parts of the world. Thus, serum D-dimer level may serve as an early marker in improving the management of patients with coronavirus disease. Keywords: corona virus disease; d-dimer; disease severity.


Subject(s)
COVID-19 , Cross-Sectional Studies , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Male , Tertiary Care Centers
8.
Thromb Res ; 213: 97-104, 2022 05.
Article in English | MEDLINE | ID: covidwho-1747542

ABSTRACT

In this single-center cohort study, we applied a panel of laboratory markers to characterize hemostatic function in 217 consecutive patients that underwent testing for COVID-19 as they were admitted to Linköping University Hospital between April and June 2020. In the 96 patients that tested positive for SARS-CoV-2 (COVID-19+), the cumulative incidences of death and venous thromboembolism were 24.0% and 19.8% as compared to 12.4% (p = 0.031) and 11.6% (p = 0.13) in the 121 patients that tested negative (COVID-19-). In COVID-19+ patients, we found pronounced increases in plasma levels of von Willebrand factor (vWF) and fibrinogen. Excess mortality was observed in COVID-19+ patients with the following aberrations in hemostatic markers: high D-dimer, low antithrombin or low plasmin-antiplasmin complex (PAP) formation, with Odds Ratios (OR) for death of 4.7 (95% confidence interval (CI95) 1.7-12.9; p = 0.003) for D-dimer >0.5 mg/L, 5.9 (CI95 1.8-19.7; p = 0.004) for antithrombin (AT) ˂0.85 kIU/l and 4.9 (CI95 1.3-18.3; p = 0.019) for PAP < 1000 µg/L. Compounding increases in mortality was observed in COVID-19+ patients with combined defects in markers of fibrinolysis and coagulation, with ORs for death of 15.7 (CI95 4.3-57; p < 0.001) for patients with PAP <1000 µg/L and D-dimer >0.5 mg/L and 15.5 (CI95 2.8-87, p = 0.002) for patients with PAP <1000 µg/L and AT ˂0.85 kIU/L. We observed an elevated fraction of incompletely degraded D-dimer fragments in COVID-19+ patients with low PAP, indicating impaired fibrinolytic breakdown of cross-linked fibrin.


Subject(s)
COVID-19 , Hemostatics , Anticoagulants , Antithrombin III , Antithrombins , Biomarkers , COVID-19 Testing , Cohort Studies , Fibrin Fibrinogen Degradation Products/metabolism , Fibrinolysin/metabolism , Fibrinolysis , Humans , SARS-CoV-2 , alpha-2-Antiplasmin
9.
Expert Rev Hematol ; 15(3): 243-251, 2022 03.
Article in English | MEDLINE | ID: covidwho-1730522

ABSTRACT

INTRODUCTION: D- Dimer levels from peripheral blood are increasingly used to assess various pathological conditions. Initially, an area for hematologists, now this analyte is evaluated more extensively from many specialties of medicine. Covid-19 infection has not only added a new dimension to D-Dimer level assessment in this disease but has also shed newer lights to the underlying pathophysiological mechanisms for its elevation in this disease. AREAS COVERED: Innate variability in measuring D- Dimer levels, Impact of various techniques in measuring D- Dimer, nonavailability of uniform controls and standards, molecular heterogeneity of the product, how it is produced. Reasons for raised D- Dimer in covid-19 infection. D- Dimer in other pathological states. Articles with relevant key words from 1990 searched in PubMed were utilized for review. EXPERT OPINION: : D-Dimer has important application in diagnosis, prognosis, management, and understanding various conditions. Its level can rise with increased coagulability of blood, sepsis, cytokine storm, snake bite, etc. Renal function, age influences its reference ranges. Units of measurement, its expression varies in different reports needing international standardization. In Covid-19 infection its levels correlate with stage of the disease, pathology, and complications.


Subject(s)
COVID-19 , COVID-19/diagnosis , Cytokine Release Syndrome/diagnosis , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Prognosis
10.
Clin Appl Thromb Hemost ; 28: 10760296221079612, 2022.
Article in English | MEDLINE | ID: covidwho-1685921

ABSTRACT

BACKGROUND: COVID-19 is a new form of acute respiratory failure leading to multiorgan failure and ICU admission. Gathered evidence suggests that a 3-fold rise in D-dimer concentrations may be linked to poor prognosis and higher mortality. PURPOSE: To describe D-dimer admission profile in severe ICU COVID19 patients and its predictive role in outcomes and mortality. METHODS: Single-center retrospective cohort study. All adult patients admitted to ICU with COVID19 were divided into 3 groups: (1) Lower-values group (D-dimer levels < 3-fold normal range value [NRV] [500ng/mL]), Intermediate-values group (D-dimer ≥3-fold and <10-fold NRV) and Higher-value group (≥10-fold NRV). RESULTS: 118 patients (mean age 63 years, 73% males) were included (N = 73 Lower-values group, N = 31 Intermediate-values group; N = 11 Higher-values group). Mortality was not different between groups (p = 0.51). Kaplan-Meier survival curves revealed no differences (p = 0.52) between groups, nor it was verified even when gender, age, ICU length of stay, and SOFA score were considered as covariables. CONCLUSIONS: In severe COVID19 patients, the D-dimer profile does not retain a predictive value regarding patients' survivability and should not be used as a surrogate of disease severity.


Subject(s)
COVID-19/blood , Fibrin Fibrinogen Degradation Products/metabolism , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
11.
J Cardiovasc Surg (Torino) ; 62(6): 548-557, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1635301

ABSTRACT

INTRODUCTION: We aimed to review the prevalence, the risk factors and the outcomes of venous thrombosis (VT) in patients hospitalized for COronaVirus Disease 19 (COVID-19). EVIDENCE ACQUISITION: Electronic bibliographic databases were searched using the words "COVID venous thrombosis". The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. EVIDENCE SYNTHESIS: The search of the literature retrieved 877 results. After assessment of full texts, 69 papers were included in the qualitative analysis and 23 of them in the quantitative evaluation. The analyzed studies included a total of 106,838 patients hospitalized for COVID-19 from January to December 2020. The pooled reported prevalence rate of VT was in median 16.7% (IQR 5.8-30%), being higher in ICU patients (60.8-85.4%). VT events were reported in about 75% of cases in the popliteal and calf veins. Signs and symptoms were present in 6.1% of cases. At quantitative evaluation, older age, D-dimer and obesity increased the odds to experience a VT (OR=3.54, 95% CI 0.65-6.43, P=0.01; OR=956.86, 95% CI 225.67-1668.05, P=0.01; OR=1.42, 95% CI 1.01-1.99, P=0.03 respectively). Female sex seemed to be protective against the odds of VT (OR=0.77, 95% CI 0.63-0.93, P=0.007). CONCLUSIONS: Among patients hospitalized for COVID-19, VT is a relatively common finding, with higher prevalence rates in ICU patients. VT occurs mostly in the distal regions of the lower limb and is asymptomatic in most cases. Older age, obesity and higher D-dimer values on admission increased the odds of VT, while female sex was protective against the odds of VT.


Subject(s)
Blood Coagulation , COVID-19/epidemiology , Venous Thrombosis/epidemiology , Age Factors , Anticoagulants/therapeutic use , Biomarkers/blood , Blood Coagulation/drug effects , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Obesity/epidemiology , Prevalence , Prognosis , Risk Assessment , Risk Factors , Sex Factors , Venous Thrombosis/blood , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy
12.
BMC Pulm Med ; 22(1): 1, 2022 Jan 03.
Article in English | MEDLINE | ID: covidwho-1608729

ABSTRACT

BACKGROUND: Quantitative evaluation of radiographic images has been developed and suggested for the diagnosis of coronavirus disease 2019 (COVID-19). However, there are limited opportunities to use these image-based diagnostic indices in clinical practice. Our aim in this study was to evaluate the utility of a novel visually-based classification of pulmonary findings from computed tomography (CT) images of COVID-19 patients with the following three patterns defined: peripheral, multifocal, and diffuse findings of pneumonia. We also evaluated the prognostic value of this classification to predict the severity of COVID-19. METHODS: This was a single-center retrospective cohort study of patients hospitalized with COVID-19 between January 1st and September 30th, 2020, who presented with suspicious findings on CT lung images at admission (n = 69). We compared the association between the three predefined patterns (peripheral, multifocal, and diffuse), admission to the intensive care unit, tracheal intubation, and death. We tested quantitative CT analysis as an outcome predictor for COVID-19. Quantitative CT analysis was performed using a semi-automated method (Thoracic Volume Computer-Assisted Reading software, GE Health care, United States). Lungs were divided by Hounsfield unit intervals. Compromised lung (%CL) volume was the sum of poorly and non-aerated volumes (- 500, 100 HU). We collected patient clinical data, including demographic and clinical variables at the time of admission. RESULTS: Patients with a diffuse pattern were intubated more frequently and for a longer duration than patients with a peripheral or multifocal pattern. The following clinical variables were significantly different between the diffuse pattern and peripheral and multifocal groups: body temperature (p = 0.04), lymphocyte count (p = 0.01), neutrophil count (p = 0.02), c-reactive protein (p < 0.01), lactate dehydrogenase (p < 0.01), Krebs von den Lungen-6 antigen (p < 0.01), D-dimer (p < 0.01), and steroid (p = 0.01) and favipiravir (p = 0.03) administration. CONCLUSIONS: Our simple visual assessment of CT images can predict the severity of illness, a resulting decrease in respiratory function, and the need for supplemental respiratory ventilation among patients with COVID-19.


Subject(s)
COVID-19/classification , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Amides/therapeutic use , Antiviral Agents/therapeutic use , Body Temperature , C-Reactive Protein/metabolism , COVID-19/drug therapy , COVID-19/physiopathology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , L-Lactate Dehydrogenase/blood , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Mucin-1/blood , Neutrophils , Predictive Value of Tests , Prognosis , Pyrazines/therapeutic use , Radiographic Image Interpretation, Computer-Assisted , Retrospective Studies , SARS-CoV-2 , Steroids/therapeutic use
13.
Thromb Haemost ; 122(2): 295-299, 2022 02.
Article in English | MEDLINE | ID: covidwho-1595734

ABSTRACT

Thromboprophylaxis with low molecular weight heparin in hospitalized patients with COVID-19 is mandatory, unless contraindicated. Given the links between inflammation and thrombosis, the use of higher doses of anticoagulants could improve outcomes. We conducted an open-label, multicenter, randomized, controlled trial in adult patients hospitalized with nonsevere COVID-19 pneumonia and elevated D-dimer. Patients were randomized to therapeutic-dose bemiparin (115 IU/kg daily) versus standard prophylaxis (bemiparin 3,500 IU daily), for 10 days. The primary efficacy outcome was a composite of death, intensive care unit admission, need of mechanical ventilation support, development of moderate/severe acute respiratory distress, and venous or arterial thrombosis within 10 days of enrollment. The primary safety outcome was major bleeding (International Society on Thrombosis and Haemostasis criteria). A prespecified interim analysis was performed when 40% of the planned study population was reached. From October 2020 to May 2021, 70 patients were randomized at 5 sites and 65 were included in the primary analysis; 32 patients allocated to therapeutic dose and 33 to standard prophylactic dose. The primary efficacy outcome occurred in 7 patients (22%) in the therapeutic-dose group and 6 patients (18%) in the prophylactic-dose (absolute risk difference 3.6% [95% confidence interval [CI], -16% -24%]; odds ratio 1.26 [95% CI, 0.37-4.26]; p = 0.95). Discharge in the first 10 days was possible in 66 and 79% of patients, respectively. No major bleeding event was registered. Therefore, in patients with COVID-19 hospitalized with nonsevere pneumonia but elevated D-dimer, the use of a short course of therapeutic-dose bemiparin does not appear to improve clinical outcomes compared with standard prophylactic doses. Trial Registration: ClinicalTrials.gov NCT04604327.


Subject(s)
COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Pneumonia/drug therapy , SARS-CoV-2/physiology , Aged , COVID-19/mortality , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Male , Middle Aged , Pneumonia/mortality , Respiration, Artificial , Severity of Illness Index , Survival Analysis , Treatment Outcome
14.
Front Immunol ; 12: 762782, 2021.
Article in English | MEDLINE | ID: covidwho-1593084

ABSTRACT

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ 2 = 34.812), and FDP (p < 0.002, χ 2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.


Subject(s)
Blood Coagulation Disorders/blood , Blood Coagulation Tests/methods , Blood Coagulation , COVID-19/complications , Adult , Aged , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/diagnosis , Blood Coagulation Factors/metabolism , COVID-19/virology , Female , Fibrin/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Homeostasis , Humans , Male , Middle Aged , Partial Thromboplastin Time , Prognosis , Protein C/metabolism , Prothrombin Time , SARS-CoV-2/genetics , SARS-CoV-2/physiology
15.
Eur J Haematol ; 108(4): 319-326, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1583574

ABSTRACT

Hospitalized patients with COVID-19 infection frequently have coagulopathy resembling disseminated intravascular coagulation (DIC). An elevation of D-dimer level is associated with a poor prognosis; however, the role of other fibrin degradation products, such as soluble fibrin monomers (SFMC), is not known. The objective of the study was to investigate the frequency and prognostic role of elevated SFMC in patients with COVID-19. In this retrospective cohort study, patients hospitalized between April 1, 2020 and December 14, 2020 at Mayo Clinic with COVID-19 infection who underwent DIC panel testing were identified. Results of laboratory tests and outcomes (thrombosis and death) within 40 days of testing were obtained via medical record review. Of 108 patients, D-dimer was elevated in 82 (75.9%) patients. Of those with elevated D-dimer, SFMC was elevated in 19/82 (23%) patients. There were 16 thrombotic events and 16 deaths during the 40-day follow-up. The incidence of overt-DIC was 4.6%. In univariate analysis, D-dimer ≥5 x highest upper limit normal (ULN) and elevated SFMC were each associated with higher 40-day mortality. However, when used in combination with D-dimer ≥5 x highest ULN, an elevated SFMC provided no further mortality predictive value. Compared to 75.9% of patients with elevated D-dimers, of those tested, only 23% had elevated SFMC. These results support the hypothesis that elevated D-dimer in COVID-19 infection is a direct consequence of endothelial damage and not overt-DIC.


Subject(s)
COVID-19/blood , Disseminated Intravascular Coagulation/blood , Fibrin Fibrinogen Degradation Products/metabolism , SARS-CoV-2/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/chemically induced , COVID-19/complications , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies
16.
Clin Appl Thromb Hemost ; 27: 10760296211057901, 2021.
Article in English | MEDLINE | ID: covidwho-1574829

ABSTRACT

IMPORTANCE: Proinflammatory and hypercoagulable states with marked elevation seen in D-Dimer levels have been accurately described in patients infected by the SARS- Cov2 even without pulmonary embolism (PE). OBJECTIVES: To compare D-dimers values in patients infected by the novel Coronavirus 2019 (COVID-19) with and without PE and to establish an optimal D-dimer cut-off to predict the occurrence of PE, which guides pulmonary computed tomography angiography (CTPA) indication. METHODS: We retrospectively enrolled all COVID-19-patients admitted between October first and November 22th, 2020, at the University Hospital Center of Mohammed VI, Oujda (Morocco), suspected to have PE and underwent a CTPA. Demographic characteristics and blood test results were compared between PE-positive and PE-negative. The receiver operating characteristics (ROC) curve was constructed to establish an optimal D-Dimer cut-off to predict the occurrence of PE. RESULTS: The study population consisted of 84 confirmed COVID-19-patients. The mean age was 64.93 years (SD 14.19). PE was diagnosed on CTPA in 31 (36.9%) patients. Clinical symptoms and in-hospital outcomes were similar in both groups except that more men had PE (p = .025). The median value of D-dimers in the group of patients with PE was significantly higher (14 680[IQR 33620-3450]ng/mL compared to the group of patients without PE 2980[IQR 6870-1600]ng/mL [P < .001]. A D-dimer at 2600 ng/mL was the optimal cut-off for predicting PE with a sensitivity of 90.3%, and AUC was .773[CI 95%, .667 -.876). CONCLUSION: A D-dimer cut-off value of 2600 ng/mL is a significant predictor of PE in COVID-19-patients with a sensitivity of 90.3%.


Subject(s)
COVID-19/complications , Fibrin Fibrinogen Degradation Products/metabolism , Pulmonary Embolism/diagnosis , Aged , Female , Humans , Male , Middle Aged , Pulmonary Embolism/physiopathology , Retrospective Studies , SARS-CoV-2
17.
J Cell Mol Med ; 26(2): 274-286, 2022 01.
Article in English | MEDLINE | ID: covidwho-1566302

ABSTRACT

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.


Subject(s)
COVID-19/blood , Cardiovascular Diseases/blood , Cardiovascular System/metabolism , SARS-CoV-2/pathogenicity , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/immunology , Cardiovascular System/pathology , Cardiovascular System/virology , Chemokine CCL2/blood , Creatine Kinase, MB Form/blood , Fibrin Fibrinogen Degradation Products/metabolism , Homocysteine/blood , Humans , Interferon-gamma/blood , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Troponin I/blood , Troponin T/blood , Tumor Necrosis Factor-alpha/blood
18.
Am J Emerg Med ; 51: 103-107, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1561013

ABSTRACT

BACKGROUND: Age adjusted serum d-dimer (AADD) with clinical decision rules have been utilized to rule out pulmonary embolism (PE) in low-risk patients; however, its use in the geriatric population has been questioned and the use of d-dimer unit (DDU) assay is uncommon. OBJECTIVE: The present study aims to compare the test characteristics of the AADD (age × 5) measured in DDU with the standard cutoff (DDU < 250) and study hospital laboratory's d-dimer cutoff (DDU < 600) in geriatric patients presenting with suspected PE. METHODS: This retrospective study enrolled patients ≥65 years old with suspected PE and d-dimer performed between January 1, 2019 and December 31, 2019 who presented to the emergency department (ED). Charts were reviewed for CTA chest and ventilation perfusion imaging results for PE. Diagnostic parameters for each cutoff were calculated for the primary outcome. RESULTS: 510 patients were included, 20 with PE. There was no significant difference between the sensitivities of AADD (100%, 95% CI: 80-100), standard cutoff (100%, 95% CI: 80-100), and hospital cutoff (90%, 95% CI: 66.9-98.2). The hospital cutoff specificity (22.7%, 95% CI: 17.1-29.3) was significantly greater than the AADD (13.4%, 95% CI: 9.1-19.2) and standard cutoff (10.8%, 95% CI: 7.0-16.3) specificities. CONCLUSIONS: In geriatric patients presenting to the ED with suspected PE, the AADD measured in DDUs maintained sensitivity with improved specificity compared to standard cutoff. In this population, the AADD would have safely reduced imaging by 19% without missing any PEs. AADD remains a valid tool with high sensitivity and negative predictive value in ruling out PE in geriatric patients.


Subject(s)
Fibrin Fibrinogen Degradation Products/metabolism , Pulmonary Embolism/blood , Pulmonary Embolism/diagnosis , Age Factors , Aged , Aged, 80 and over , Emergency Service, Hospital , Female , Humans , Male , Retrospective Studies , Sensitivity and Specificity
19.
Dis Markers ; 2021: 6304189, 2021.
Article in English | MEDLINE | ID: covidwho-1553755

ABSTRACT

BACKGROUND: Early identification of patients with severe coronavirus disease (COVID-19) at an increased risk of progression may promote more individualized treatment schemes and optimize the use of medical resources. This study is aimed at investigating the utility of the C-reactive protein to albumin (CRP/Alb) ratio for early risk stratification of patients. METHODS: We retrospectively reviewed 557 patients with COVID-19 with confirmed outcomes (discharged or deceased) admitted to the West Court of Union Hospital, Wuhan, China, between January 29, 2020 and April 8, 2020. Patients with severe COVID-19 (n = 465) were divided into stable (n = 409) and progressive (n = 56) groups according to whether they progressed to critical illness or death during hospitalization. To predict disease progression, the CRP/Alb ratio was evaluated on admission. RESULTS: The levels of new biomarkers, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CRP/Alb ratio, and systemic immune-inflammation index, were higher in patients with progressive disease than in those with stable disease. Correlation analysis showed that the CRP/Alb ratio had the strongest positive correlation with the sequential organ failure assessment score and length of hospital stay in survivors. Multivariate logistic regression analysis showed that percutaneous oxygen saturation (SpO2), D-dimer levels, and the CRP/Alb ratio were risk factors for disease progression. To predict clinical progression, the areas under the receiver operating characteristic curves of Alb, CRP, CRP/Alb ratio, SpO2, and D-dimer were 0.769, 0.838, 0.866, 0.107, and 0.748, respectively. Moreover, patients with a high CRP/Alb ratio (≥1.843) had a markedly higher rate of clinical deterioration (log - rank p < 0.001). A higher CRP/Alb ratio (≥1.843) was also closely associated with higher rates of hospital mortality, ICU admission, invasive mechanical ventilation, and a longer hospital stay. CONCLUSION: The CRP/Alb ratio can predict the risk of progression to critical disease or death early, providing a promising prognostic biomarker for risk stratification and clinical management of patients with severe COVID-19.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/diagnosis , Coronary Disease/diagnosis , Hypertension/diagnosis , Pulmonary Disease, Chronic Obstructive/diagnosis , SARS-CoV-2/pathogenicity , Serum Albumin, Human/metabolism , Aged , Area Under Curve , Biomarkers/blood , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , China/epidemiology , Comorbidity , Coronary Disease/epidemiology , Coronary Disease/mortality , Coronary Disease/virology , Disease Progression , Early Diagnosis , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Length of Stay/statistics & numerical data , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Prognosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/mortality , Pulmonary Disease, Chronic Obstructive/virology , ROC Curve , Retrospective Studies , SARS-CoV-2/growth & development , Severity of Illness Index , Survival Analysis
20.
Ann Hematol ; 101(3): 513-520, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1549412

ABSTRACT

Hyperferritinemia comes to light frequently in general practice. However, the characteristics of COVID-19-associated hyperferritinemia and the relationship with the prognosis were not well described. The retrospective study included 268 documented COVID-19 patients. They were divided into the hyperferritinemia group (≥ 500 µg/L) and the non-hyperferritinemia group (< 500 µg/L). The prevalence of fever and thrombocytopenia and the proportion of patients with mechanical ventilator support and in-hospital death were much higher in the hyperferritinemia group (P < 0.001). The hyperferritinemia patients showed higher median IL-6, D-dimer, and hsCRP (P < 0.001) and lowered FIB level (P = 0.036). The hyperferritinemia group had a higher proportion of patients with AKI, ARDS, and CSAC (P < 0.001). According to the multivariate analysis, age, chronic pulmonary disease, and hyperferritinemia were found to be significant independent predictors for in-hospital mortality [HR 1.041 (95% CI 1.015-1.068), P = 0.002; HR 0.427 (95% CI 0.206-0.882), P = 0.022; HR 6.176 (95% CI 2.447-15.587), P < 0.001, respectively]. The AUROC curve was 0.88, with a cut-off value of ≥ 971 µg/L. COVID-19 patients with hyperferritinemia had a high proportion of organ dysfunction, were more likely to show hyper-inflammation, progressed to hemophagocytic lymphohistiocytosis, and indicated a higher proportion of death.


Subject(s)
COVID-19/blood , Hyperferritinemia/blood , Phagocytosis , SARS-CoV-2/metabolism , Aged , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/mortality , Female , Fibrin Fibrinogen Degradation Products/immunology , Fibrin Fibrinogen Degradation Products/metabolism , Hospital Mortality , Humans , Hyperferritinemia/etiology , Hyperferritinemia/immunology , Hyperferritinemia/mortality , Inflammation/blood , Inflammation/immunology , Inflammation/mortality , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , Prevalence , Retrospective Studies , SARS-CoV-2/immunology
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