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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
BMC Nephrol ; 22(1): 224, 2021 06 16.
Article in English | MEDLINE | ID: covidwho-1277921

ABSTRACT

BACKGROUND: Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. METHODS: Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. RESULTS: Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). CONCLUSION: Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.


Subject(s)
Acute Kidney Injury , Anticoagulants/therapeutic use , COVID-19 , Intensive Care Units/statistics & numerical data , Thrombophilia , Thrombosis/prevention & control , Acute Kidney Injury/complications , Acute Kidney Injury/diagnosis , Acute Kidney Injury/prevention & control , Acute Kidney Injury/virology , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Female , Hospital Mortality , Humans , Male , Preexisting Condition Coverage/statistics & numerical data , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Thrombophilia/diagnosis , Thrombophilia/prevention & control , Thrombophilia/virology , Thrombosis/blood , Thrombosis/etiology , United Kingdom/epidemiology
8.
J Thromb Thrombolysis ; 52(2): 497-503, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1188149

ABSTRACT

The coronavirus disease 2019 (COVID-19) increases thrombotic risk. The mechanisms that lead to this prothrombotic state are not well established. The main aim was to evaluate the von Willebrand factor (VWF) antigen and plasma ADAMTS13 activity as endothelial injury markers in COVID-19. We present a prospective study in COVID-19 patients recruited in our institution. VWF antigen, ADAMTS13 activity, D-dimer, and fibrinogen were measured during the first week once COVID-19 was diagnosed. Fifty COVID-19 inpatients [44% in the intensive care unit (ICU)] and 102 COVID-19 outpatients were enrolled. Thirty age and gender matched non-COVID-19 ward inpatients and 30 non-COVID-19 healthy individuals were recruited. The COVID-19 inpatients had higher D-dimer, fibrinogen, and VWF antigen levels and a lower ADAMTS13 activity compared with the COVID-19 outpatients (p < 0.05). ICU patients had higher D-dimer and VWF antigen levels compared with the ward patients and the lowest ADAMTS13 activity (p < 0.05). An imbalance in VWF antigen/ADAMTS13 ratio was observed in COVID-19, reaching the highest in ICU patients. In contrast to other ward non-COVID-19 inpatients, a significative reduction in ADAMTS13 activity was observed in all COVID-19 patients. There is an increase in VWF antigen and an ADAMTS13 activity reduction in COVID-19 related to disease severity and could predict poor clinical outcomes. The ADAMTS13 activity reduction could be a marker associated with COVID-19 compared to other non-critical medical conditions.


Subject(s)
ADAMTS13 Protein/blood , COVID-19 , Endothelium, Vascular , Risk Assessment , Thrombophilia , von Willebrand Factor/analysis , Aged , Ambulatory Care/statistics & numerical data , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , Correlation of Data , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Prospective Studies , Risk Assessment/methods , Risk Assessment/statistics & numerical data , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spain/epidemiology , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/virology
9.
Clin Appl Thromb Hemost ; 27: 1076029621996445, 2021.
Article in English | MEDLINE | ID: covidwho-1148196

ABSTRACT

BACKGROUND: To investigate the factors associated with elevated fibrinogen (Fbg) levels in COVID-19 patients with and without diabetes (DM) and impaired fasting glucose (IFG). METHODS: According to whether or not their glucose metabolism was impaired, COVID-19 patients were subdivided into 2 groups: 1) with DM and IFG, 2) control group. Their demographic data, medical history, signs and symptoms, laboratory results, and final clinical results were analyzed retrospectively. RESULTS: 28 patients (16.3%) died during hospitalization, including 21 (29.2%) in group 1 and 7 (7.0%) in group 2 (P < 0.001). Fbg levels in groups 1 and 2 were higher than the normal range, at 5.6 g/L (IQR 4.5-7.2 g/L) and 5.0 g/L (IQR 4.0-6.1 g/L), respectively (P = 0.009). Serum ferritin levels, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), triglycerides (TG) were significantly increased in group 1 compared to those in the control. TG levels were 1.3 mmol/L in the control, while that in group 1 was 1.8 mmol/L. Multiple linear regression showed that the predicting factors of Fbg in the control group were serum ferritin and CRP, R2 = 0.295; in group 1, serum ferritin, CRP, and TG, R2 = 0.473. CONCLUSIONS: Fbg in all COVID-19 patients is related to serum ferritin and CRP involved in inflammation. Furthermore, in COVID-19 patients with insulin resistance, Fbg is linearly positively correlated with TG. This suggests that regulation of TG, insulin resistance, and inflammation may reduce hypercoagulability in COVID-19 patients, especially those with insulin resistance.


Subject(s)
Blood Glucose/analysis , COVID-19/blood , Diabetes Mellitus/blood , Fasting/blood , Fibrinogen/analysis , Insulin Resistance , Thrombophilia/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Blood Coagulation , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/virology , Diabetes Mellitus/diagnosis , Female , Ferritins/blood , Humans , Inflammation Mediators/blood , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Thrombophilia/virology , Triglycerides/blood , Up-Regulation , Young Adult
10.
Thromb Res ; 201: 84-89, 2021 05.
Article in English | MEDLINE | ID: covidwho-1117704

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is associated with a clear prothrombotic phenotype. Although the exact pathophysiological mechanisms are not yet fully understood, thrombosis is clearly a highly important in the prognosis and outcome of COVID-19. As such, there is a need for diagnostic analysis and quantification of the coagulation potential in these patients, both at diagnosis and follow-up. Global coagulation assays like thrombin generation (TG) and rotational thromboelastometry (ROTEM) might be suitable in estimating COVID-19 associated coagulopathy and thrombosis risk. Therefore, we aimed at validating both assays for samples with high levels of fibrinogen and in the presence of anticoagulant heparins, such as commonly observed for COVID-19 ICU patients. MATERIALS AND METHODS: Calibrated Automated Thrombography (CAT) was optimized to assess plasma thrombin generation in the presence of heparins. The final conditions with either 10 µg/mL Ellagic acid (EA) or PPP Reagent HIGH (high tissue factor; HPPH) were validated according to the EP5 protocol for within-run and between-run variability. Overall variability was well below 10%. To estimate the influences of heparins and high fibrinogen levels, CAT was performed on spiked plasma aliquots from 13 healthy volunteers. Comparable to the CAT method, tPA-ROTEM was used to validate the effect of high fibrinogen and heparins on clotting time, clot firmness and clot lysis parameters. RESULTS: Our adjusted COVID-19 assay showed a heparin dose dependent decrease in peak height and endogenous thrombin potential (ETP) for both EA and HPPH triggered variants. High fibrinogen did not alter the inhibitory effect of either LMWH or UFH, nor did it influence the peak height or ETP in any of the conditions. The tPA-ROTEM showed a significant prolongation in clotting time with the additions of heparin, which normalized with the addition of high fibrinogen. MCF was markedly increased in all hyperfibrinogenemic conditions. A trend towards increased lysis time and, thus, decreased fibrinolysis was observed. CONCLUSION: Thrombin generation and tPA-ROTEM protocols for measurements in the COVID-19 populations were adjusted and validated. The adjusted thrombin generation assay shows good sensitivity for measurements in heparin spiked plasma. High levels of fibrinogen did not alter the assay or the effectiveness of heparins as measured in this assay. t-PA ROTEM was effective in measurement of both high fibrinogen and heparins spiked samples and was sensitive to the expected relevant coagulant changes by these conditions. No clear fibrinolytic effect was observed in different conditions.


Subject(s)
COVID-19 , Thrombophilia , Blood Coagulation Tests , Heparin, Low-Molecular-Weight , Humans , RNA, Viral , SARS-CoV-2 , Thrombelastography , Thrombophilia/diagnosis
12.
Rheumatology (Oxford) ; 60(1): 34-47, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1093595

ABSTRACT

While prompt diagnosis of vasculitis is important, recognition of vasculitis mimics is equally essential. As in the case of vasculitis, an approach to mimics based on the anatomic size of vessels can be useful. Infections can mimic vasculitis of any vessel size, including the formation of aneurysms and induction of ANCAs. Genetic disorders and vasculopathies are important considerations in large and medium vessel vasculitis. Cholesterol emboli, thrombotic conditions and calciphylaxis typically affect the medium and small vessels and, like vasculitis, can cause cutaneous, renal and CNS manifestations. Reversible cerebral vasoconstriction syndrome is important to distinguish from primary angiitis of the CNS. As an incorrect diagnosis of vasculitis can result in harmful consequences, it is imperative that the evaluation of suspected vasculitis includes consideration of mimics. We discuss the above mimics and outline a systematic and practical approach for differentiating vasculitis from its mimics.


Subject(s)
Vasculitis/diagnosis , Diagnosis, Differential , Embolism, Cholesterol/diagnosis , Endocarditis/diagnosis , Humans , Thrombophilia/diagnosis
13.
Sci Rep ; 11(1): 1793, 2021 01 19.
Article in English | MEDLINE | ID: covidwho-1065942

ABSTRACT

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.


Subject(s)
COVID-19/pathology , Thrombophilia/diagnosis , Virus Diseases/pathology , Adult , COVID-19/complications , COVID-19/virology , Female , Humans , Male , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Partial Thromboplastin Time , Prothrombin Time , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombophilia/complications , Virus Diseases/complications
14.
Int J Lab Hematol ; 43(1): 123-130, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1066694

ABSTRACT

INTRODUCTION: Patients with COVID-19 are known to have a coagulopathy with a thrombosis risk. It is unknown whether this is due to a generalized humoral prothrombotic state or endothelial factors such as inflammation and dysfunction. The aim was to further characterize thrombin generation using a novel analyser (ST Genesia, Diagnostica Stago, Asnières, France) and a panel of haematological analytes in patients with COVID-19. METHODS: Platelet poor plasma of 34 patients with noncritical COVID-19 was compared with 75 patients with critical COVID-19 (as defined by WHO criteria) in a retrospective study by calibrated automated thrombography and ELISA. Patients were matched for baseline characteristics of age and gender. RESULTS: Critical patients had significantly increased fibrinogen, CRP, interleukin-6 and D-dimer compared to noncritical patients. Thrombin generation, in critical patients, was right shifted without significant differences in peak, velocity index or endogenous thrombin potential. Tissue plasminogen activator (tPA), tissue factor pathway inhibitor (TFPI) and vascular endothelial growth factor (VEGF) were significantly increased in the critical versus noncritical patients. Critically ill patients were on haemodiafiltration (31%; heparin used in the circuit) or often received escalated prophylactic low-molecular weight heparin. CONCLUSION: These results confirm increased fibrinogen and D-dimer in critical COVID-19-infected patients. Importantly, disease severity did not increase thrombin generation (including thrombin-antithrombin complexes and prothrombin fragment 1 + 2) when comparing both cohorts; counter-intuitively critical patients were hypocoaguable. tPA, TFPI and VEGF were increased in critical patients, which are hypothesized to reflect endothelial dysfunction and/or contribution of heparin (which may cause endothelial TFPI/tPA release).


Subject(s)
Blood Coagulation Tests/methods , COVID-19/blood , Pandemics , SARS-CoV-2 , Thrombin/biosynthesis , Thrombophilia/etiology , Adult , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Blood Coagulation Tests/instrumentation , COVID-19/complications , Critical Illness , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrinogen/analysis , Humans , Lipoproteins/analysis , Male , Middle Aged , Platelet Count , Retrospective Studies , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Tissue Plasminogen Activator/analysis , Vascular Endothelial Growth Factor A/blood , Young Adult
15.
Aust Crit Care ; 34(2): 160-166, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1053209

ABSTRACT

BACKGROUND: A high number of thrombotic complications have been reported in critically ill patients with coronavirus disease 2019 (COVID-19) and appear to be related to a hypercoagulable state. Evidence regarding detection, management, and monitoring of COVID-19-associated coagulopathy is still missing. We propose to describe the thrombus viscoelastic properties to investigate the mechanisms of hypercoagulability in patients with COVID-19. METHODS: Thromboelastography (TEG) was performed in 24 consecutive patients admitted to a single intensive care unit for COVID-19 pneumonia, and 10 had a second TEG before being discharged alive from the intensive care unit. RESULTS: Compared with a group of 20 healthy participants, patients with COVID-19 had significantly decreased values of reaction time, coagulation time, and lysis index and increased values of α angle, maximum amplitude, clot strength, and coagulation index. Velocity curves were consistent with increased generation of thrombin. These values persisted in surviving patients despite their good clinical course. DISCUSSION: In patients with COVID-19, TEG demonstrates a complex and prolonged hypercoagulable state including fast initiation of coagulation and clot reinforcement, low fibrinolysis, high potential of thrombin generation, and high fibrinogen and platelet contribution. The antithrombotic strategy in patients with COVID-19 during intensive care hospitalisation and after discharge should be investigated in further studies.


Subject(s)
COVID-19/blood , Pneumonia, Viral/blood , Thrombelastography , Thrombophilia/diagnosis , Thrombophilia/virology , Aged , Female , Humans , Intensive Care Units , Male , Middle Aged , Pneumonia, Viral/virology , SARS-CoV-2
16.
Thromb Res ; 199: 132-142, 2021 03.
Article in English | MEDLINE | ID: covidwho-1014833

ABSTRACT

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


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Heparin, Low-Molecular-Weight/therapeutic use , Thrombosis/drug therapy , Thrombosis/etiology , Aged , Aged, 80 and over , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purification , Thrombophilia/diagnosis , Thrombophilia/drug therapy , Thrombophilia/etiology , Thrombosis/diagnosis , Venous Thromboembolism/diagnosis , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
17.
Am J Med ; 134(5): 688-690, 2021 05.
Article in English | MEDLINE | ID: covidwho-973806

ABSTRACT

BACKGROUND: The association between coronavirus disease 2019 (COVID-19) and hypercoagulability has been extensively described, and pulmonary embolism is a recognized complication of COVID-19. Currently, the need for computed tomography pulmonary angiogram (CTPA) relies on the Wells score and serum D-dimer levels. However, because COVID-19 patients have a different thrombotic and inflammatory milieu, the usefulness of the Wells score deserves further exploration for this patient population. We aimed to explore the ability of the Wells score to predict pulmonary embolism in patients with COVID-19. METHODS: In this retrospective study, patients found to have a CTPA and a COVID-19 diagnosis during the same admission were selected for analysis. Age and sex, CTPA results, and associated D-dimer levels were entered in a database. The Wells score sensitivity and specificity were calculated at different values, and the area under the curve of the receiver operating characteristic curve measured. RESULTS: Of 459 patients with COVID-19, 64 had a CTPA and 12 (19%) had evidence of pulmonary embolism. Previous or current evidence of deep vein thrombosis, a Wells score above 4 points, and serum D-dimer levels 5 times above age-adjusted upper normal values were associated with pulmonary embolism. However, only 33% of patients with pulmonary embolism had a Wells score of 4 points or higher. The area under the curve of the receiver operating characteristic showed non-discriminating values (0.54) CONCLUSIONS: Although a Wells score of 4 or more points predicted pulmonary embolism in our cohort, the outcome can be present even with lower scores.


Subject(s)
COVID-19 , Computed Tomography Angiography/methods , Fibrin Fibrinogen Degradation Products/analysis , Pulmonary Embolism/diagnosis , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Pulmonary Embolism/blood , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , ROC Curve , Research Design/standards , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , Severity of Illness Index , Thrombophilia/diagnosis , Thrombophilia/etiology , United States/epidemiology
18.
Br J Anaesth ; 126(3): 590-598, 2021 03.
Article in English | MEDLINE | ID: covidwho-965444

ABSTRACT

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor. METHODS: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT. RESULTS: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test. CONCLUSION: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.


Subject(s)
COVID-19/blood , COVID-19/epidemiology , Critical Illness/epidemiology , Fibrinolysis/drug effects , Thrombophilia/blood , Thrombophilia/epidemiology , Adult , Aged , Anticoagulants/administration & dosage , Blood Coagulation Tests/methods , COVID-19/diagnosis , Female , Fibrinolysis/physiology , Humans , Male , Middle Aged , Retrospective Studies , Thrombophilia/diagnosis , Tissue Plasminogen Activator/administration & dosage
20.
J Vasc Surg Venous Lymphat Disord ; 9(3): 585-591.e2, 2021 05.
Article in English | MEDLINE | ID: covidwho-813723

ABSTRACT

BACKGROUND: Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. METHODS: We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. RESULTS: The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). CONCLUSIONS: Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.


Subject(s)
COVID-19 , Fibrin Fibrinogen Degradation Products/analysis , Pulmonary Embolism , Respiration, Artificial/methods , Venous Thrombosis , COVID-19/blood , COVID-19/complications , COVID-19/epidemiology , Computed Tomography Angiography/methods , Female , Humans , Incidence , Male , Middle Aged , Philadelphia/epidemiology , Prognosis , Pulmonary Embolism/diagnosis , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Thrombophilia/blood , Thrombophilia/diagnosis , Thrombophilia/etiology , Ultrasonography, Doppler, Duplex/methods , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
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