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1.
Int J Lab Hematol ; 44(5): 823-830, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2295313

ABSTRACT

BACKGROUND: COVID-19 associated coagulopathy (CAC) can either be localized or systemic hypercoagulable state with increased risk of thromboembolism. This study looked into the usefulness of Thromboelastography (TEG) and the velocity curve (V-curve) derivative from TEG in diagnosing and differentiating different stages of CAC. MATERIALS AND METHODS: A prospective single cohort study of RT-PCR confirmed COVID-19 patients was carried out for 2 weeks. Severe COVID-19 patients in the adult critical care units with a TEG report were recruited for the study. Citrated kaolin TEG was performed on the day of admission before anticoagulation. TEG parameters included were R and K time, alpha angle, maximum amplitude, clotting index, lysis at 30 min. The first-degree velocity curve of TEG is plotted as V-curve which extrapolates thrombus generation potential. Parameters analyzed were the maximum rate of thrombus generation as well as thrombus generated (TG). RESULTS: The study included 43 patients with an average age of 58.34 (±15.35). TEG as well as V-curve of all the patients were hypercoagulable compared with age-matched reference range. We had 79.06% of patients in hypercoagulable stage. The mortality rate was 32.56% and 30.23% developed thrombotic incidents. Patients who succumbed to death had prolonged PT, aPTT, MA, Ly30, with a reduced TG (p < .05). The presence of fibrinolysis was associated with thromboembolism (OR = 6.76, CI = 1.48-25.82). Repeat TEG was done randomly in 11 patients and revealed a persistent hypercoagulable stage with increasing fibrinolysis activity. CONCLUSION: TEG is a useful tool in diagnosing and categorizing Coagulopathy associated with COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thromboembolism , Thrombophilia , Adult , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/etiology , COVID-19/complications , COVID-19/diagnosis , COVID-19 Testing , Cohort Studies , Humans , Middle Aged , Prospective Studies , Thrombelastography , Thrombophilia/complications , Thrombophilia/etiology
2.
Intern Med ; 62(5): 717-722, 2023 Mar 01.
Article in English | MEDLINE | ID: covidwho-2287359

ABSTRACT

Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU). Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge. Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008]. Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Adult , Humans , Thrombelastography/methods , Retrospective Studies , Blood Coagulation Tests , Fibrinogen
3.
Pharmacotherapy ; 43(3): 196-204, 2023 03.
Article in English | MEDLINE | ID: covidwho-2253213

ABSTRACT

STUDY OBJECTIVE: Thromboelastography (TEG) offers a more dynamic assessment of hemostasis over activated partial thromboplastin time (aPTT). However, the clinical utility of TEG in monitoring bivalirudin during extracorporeal membrane oxygenation (ECMO) remains unknown. The purpose of this study was to evaluate the correlation between aPTT and TEG in adult ECMO patients anticoagulated with bivalirudin. DESIGN: Multicenter, retrospective, cohort study conducted over a 2-year period. SETTING: Two academic university medical centers (Banner University Medical Center) in Phoenix and Tucson, AZ. PATIENTS: Adult patients requiring ECMO and bivalirudin therapy with ≥1 corresponding standard TEG and aPTT plasma samples drawn ≤4 h of each other were included. The primary endpoint was to determine the correlation coefficient between the standard TEG reaction (R) time and bivalirudin aPTT serum concentrations. MEASUREMENTS AND MAIN RESULTS: A total of 104 patients consisting of 848 concurrent laboratory assessments of R time and aPTT were included. A moderate correlation between TEG R time and aPTT was demonstrated in the study population (r = 0.41; p < 0.001). Overall, 502 (59.2%) concurrent assessments of TEG R time and aPTT values showed agreement on whether they were sub-, supra-, or therapeutic according to the institution's classification for bivalirudin. The 42.2% (n = 271/642) discordant TEG R times among "therapeutic" aPTT were almost equally distributed between subtherapeutic and supratherapeutic categories. CONCLUSIONS: Moderate correlation was found between TEG R time and aPTT associated with bivalirudin during ECMO in critically ill adults. Further research is warranted to address the optimal test to guide clinical decision-making for anticoagulation dosing in ECMO patients.


Subject(s)
Extracorporeal Membrane Oxygenation , Thrombelastography , Humans , Adult , Partial Thromboplastin Time , Heparin , Anticoagulants/therapeutic use , Retrospective Studies , Cohort Studies , Critical Illness/therapy , Hirudins , Peptide Fragments , Recombinant Proteins/therapeutic use
4.
Semin Thromb Hemost ; 48(7): 769-784, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2239425

ABSTRACT

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.


Subject(s)
Blood Coagulation Disorders , Hemostatics , Humans , Thrombelastography/methods , Blood Coagulation Tests , Hemostasis , Blood Coagulation Disorders/therapy , Hemorrhage/therapy
5.
PLoS One ; 18(1): e0269738, 2023.
Article in English | MEDLINE | ID: covidwho-2196903

ABSTRACT

INTRODUCTION: Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation. AIM: Assess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin. METHODS: COVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested for the same period. RESULTS: 33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p = 0.73) between patients admitted to a ward or escalated to ITU. Significant correlations were observed between FIBA5 (r = 0.62; p<0.00), FIBCFT (r = -0.57; p<0.00), FIBMCF (r = 0.64; p<0.00) and INMCF (r = 0.57; p<0.00) and calprotectin. CONCLUSION: COVID-19 patients were hypercoagulable on admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.


Subject(s)
COVID-19 , Thrombophilia , Humans , Thrombelastography , COVID-19/complications , COVID-19/diagnosis , Pilot Projects , Thrombophilia/diagnosis , Inflammation
6.
Clin Appl Thromb Hemost ; 28: 10760296221131801, 2022.
Article in English | MEDLINE | ID: covidwho-2162205

ABSTRACT

Acute ischemic stroke (AIS), characterized by high morbidity and mortality, has imposed a considerable burden on society. Despite rapid development in the treatment of AIS, there is still a high risk of recurrence. Furthermore, there is a time delay in waiting for the results of conventional coagulation tests in candidate patients for intravenous thrombolysis therapy. Heterogeneous responses to antiplatelet, intravascular thrombolysis, and endovascular therapies also worsen the situation. Thromboelastography (TEG), as a global and portable detection method for hemostasis, facilitates clinicians in disease monitoring, treatment evaluation, and prognosis prediction in AIS. In this narrative review, we provided a comprehensive summary of the clinical application of TEG in ischemic stroke and gave insights to further studies.


Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Humans , Thrombelastography , Blood Coagulation Tests , Thrombolytic Therapy/methods , Treatment Outcome
7.
Clin Hemorheol Microcirc ; 82(2): 183-191, 2022.
Article in English | MEDLINE | ID: covidwho-2141602

ABSTRACT

BACKGROUND: A significant degree of mortality and morbidity in Covid-19 is due to thromboembolic disease. Coagulopathy has been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. OBJECTIVE: We sought to investigate whether coagulation markers can predict severity and how they change over the disease course. METHODS: Patients presenting to a single University Teaching Hospital were recruited and followed up if PCR was positive. Alongside routine blood testing, Rotational Thromboelastometry (ROTEM) was performed. Outcome data was recorded for all patients, and ROTEM values were compared across outcome groups. RESULTS: Extem and Intem Maximum Lysis were significantly reduced in those who died or required an ICU admission, indicating a reduced ability to break down clot mass in the most critically unwell patients. CONCLUSION: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of Covid-19 compared with those who survive a hospital stay to discharge was the extent to which fibrinolysis could occur. Mortality and morbidity in Covid-19 infection appears in part driven by an inability to break down clot mass.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Humans , Fibrinolysis , Thrombelastography , Blood Coagulation Tests
8.
PLoS One ; 17(11): e0277544, 2022.
Article in English | MEDLINE | ID: covidwho-2140651

ABSTRACT

OBJECTIVE: COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. DESIGN: Prospective observational study. SETTING: Monocentric, intensive care, University Hospital of Clermont Ferrand, France. PATIENTS: Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. INTERVENTIONS: Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 µg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. MEASUREMENTS AND MAIN RESULTS: Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. CONCLUSIONS: Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Hemostatics , Thromboembolism , Thrombophilia , Humans , Prospective Studies , Critical Illness , COVID-19/complications , Thrombophilia/complications , Thrombelastography
9.
Medicine (Baltimore) ; 101(26): e29738, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-2051689

ABSTRACT

BACKGROUND: It was repeatedly demonstrated that patients with severe COVID-19 pneumonia, as well as patients with type 2 diabetes (T2D) have higher risk of thromboembolic complications. Rotational thromboelastometry (ROTEM®) is a viscoelastic hemostatic assay which allows complex assessment of hemostasis in whole blood. The aim of this study was to compare changes in hemostasis measured by ROTEM® in diabetic and nondiabetic patients with mild COVID-19 pneumonia. METHODS: We performed a pilot, prospective, observational study and enrolled 33 consecutive patients (14 with T2D and 19 nondiabetic ones) admitted to regular ward with mild COVID-19 pneumonia. The control group consisted from 11 healthy, nondiabetic blood donors. Blood samples were tested with ROTEM® using INTEM® and EXTEM® reagents. RESULTS: We detected significant differences in EXTEM® clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF) comparing patients with mild COVID-19 pneumonia and healthy donors. However, there were no significant differences in EXTEM®, INTEM®, and HEPTEM® parameters (CT, CFT, and MCF) according to diabetes status. CONCLUSIONS: Our study demonstrated hypercoagulation in patients with mild COVID-19 pneumonia. T2D did not affected ROTEM® parameters in patients with mild COVID-19 pneumonia.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Blood Coagulation Tests , COVID-19/complications , Diabetes Mellitus, Type 2/complications , Humans , Prospective Studies , Thrombelastography
10.
Clin Lab ; 68(8)2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1988445

ABSTRACT

BACKGROUND: According to recent studies, thrombotic complications frequently occur in Coronavirus Disease-19 (COVID-19) and are associated with increasing disease severity and poor prognosis. However, conventional coagulation assays are unable to identify these patients' hypercoagulable states, raising questions about the appropriate assessment tool. We aimed to evaluate coagulation abnormalities in patients with different severity of CO-VID-19 using viscoelastic tests. METHODS: This was a single center retrospective observational study in a group of 50 adult patients with SARS-COV-2 infection and different severity of pneumonia (20 moderate, 30 severe). Coagulation status was evaluated using rotational thromboelastometry (ROTEM®) in conjunction with conventional coagulation assays (platelet count, PT, aPTT, fibrinogen, and D-dimer levels). RESULTS: Shorter than normal EXTEM CFT, higher than normal A10 and MCF in INTEM, EXTEM, and FIBTEM and higher than normal α-angle were classified as markers of hypercoagulable state. Forty-four (88%) patients had at least two hypercoagulable ROTEM parameters. Seven patients developed thromboembolic complications. All were classified as having severe COVID-19 pneumonia. With increment increases in disease severity, we observed an increase in the number of patients with hypercoagulable parameters and higher INTEM, EXTEM, and FIBTEM MCF but without being statistically significant. On the other hand, we noted a significant decrement of PT (p = 0.039), higher fibrinogen (p = 0.001), higher D dimer (p < 0.001), and shorter CT EXTEM (p < 0.001). CONCLUSIONS: Our findings support the presence of a hypercoagulable state in COVID-19 patients, especially in the severe forms. It also highlights the role of viscoelastic tests in assessing COVID-19 coagulopathy and, therefore, their potential use in thrombophrophylactic management.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Thrombophilia , Adult , Blood Coagulation Disorders/diagnosis , Blood Coagulation Tests , COVID-19/complications , COVID-19/diagnosis , Fibrinogen , Humans , SARS-CoV-2 , Thrombelastography , Thrombophilia/complications , Thrombophilia/diagnosis
11.
Clin Appl Thromb Hemost ; 28: 10760296221112085, 2022.
Article in English | MEDLINE | ID: covidwho-1968503

ABSTRACT

A high risk of thrombotic complications has been observed among severely ill COVID-19 patients. Viscoelastic tests (VET) have shown a hypercoagulable profile in these patients, although so far there is no clear evidence on the use of these tools as predictors of risk in the clinical course of patients. In this study we aimed to evaluate the association between Quantra® sonorheometry VET parameters, standard coagulation tests and inflammatory markers in 69 patients with COVID-19 on hospital admission with disease severity and outcome. Inflammatory markers were elevated in a high percentage of patients, as were coagulation-related parameters such as fibrinogen and D-dimer levels. Quantra® sonorheometry analysis revealed increased clot stiffness (CS), especially due to increased fibrinogen contribution (FCS) in 63.7%. Analysis of clot stability to lysis (CSL) on the Quantra showed a value of 100%, suggesting hypofibrinolysis, in 32.4%. Age > 65 years, elevated values of fibrinogen, D-dimer, LDH, increased CS and CSL were significantly associated with worsening disease. The combination of elevated FCS and D-dimer values showed a particularly high prognostic value in distinguishing patients with severe symptomatology. In conclusion, FCS measured by Quantra® system and its combination with D-dimer could be established as a powerful tool to identify poor prognosis in COVID-19 patients on hospital admission.


Subject(s)
COVID-19 , Thrombelastography , Aged , Biomarkers , Blood Coagulation Tests , Fibrin Fibrinogen Degradation Products , Fibrinogen/analysis , Humans , Prognosis
12.
Am Surg ; 88(8): 1970-1975, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1932939

ABSTRACT

BACKGROUND: Limitations in available donors have dramatically reduced plasma availability over the past several decades, concurrent with increasing demand for some types of plasma. Plasma from female donors who are pregnant or taking oral contraceptives often has a green appearance, which frequently results in these units being discarded. This pilot study aimed to evaluate the hemostatic potential of green compared to standard-color plasma. MATERIALS AND METHODS: Plasma from twelve blood group-matched female and twelve male donors was obtained from the local blood center. Six of the female and all of the male units of plasma had a normal appearance (STANDARD), while six of the female units were grossly green (GREEN). The hemostatic potential was evaluated by thrombelastography (TEG), calibrated automated thrombogram (CAT), and coagulation factor level measurements. Univariate analysis was performed using Wilcoxon Rank-Sum. RESULTS: GREEN plasma was more procoagulant for all TEG values (r-value, k-time, angle, mA) when compared to STANDARD plasma. Differences were also observed in coagulation factor levels, with GREEN plasma having higher than STANDARD (factors II; VII, IX; X, XI, Protein S, and plasminogen); conversely, GREEN plasma had a longer lag time in CAT. DISCUSSION: This pilot study demonstrates that female donors with green plasma have a superior hemostatic profile than standard plasma. GREEN plasma should be further investigated for its safety profile and hemostatic potential, so if it is found to be a safe and functionally non-inferior product, it should be actively re-introduced for transfusion in bleeding patients.


Subject(s)
Hemostatics , Blood Coagulation Factors , Female , Hemostasis , Humans , Male , Pilot Projects , Pregnancy , Thrombelastography/methods
13.
Am Surg ; 88(7): 1689-1693, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1892040

ABSTRACT

BACKGROUND: Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The "death diamond" (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. METHODS: A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. RESULTS: A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. DISCUSSION: The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.


Subject(s)
Blood Coagulation Disorders , Wounds and Injuries , Biomarkers , Humans , Retrospective Studies , Thrombelastography/methods , Trauma Centers , Wounds and Injuries/diagnosis , Wounds and Injuries/therapy
14.
Eur Rev Med Pharmacol Sci ; 26(9): 3399-3405, 2022 05.
Article in English | MEDLINE | ID: covidwho-1856627

ABSTRACT

OBJECTIVE: COVID-19 patients have been shown to be hypercoagulable, increasing the risk for thromboembolic events. The kinetics of the blood coagulation process were monitored daily throughout hospitalization in COVID-19 positive patients. PATIENTS AND METHODS: Thromboelastography (TEG) was used to assess blood coagulation in 48 adult patients hospitalized for COVID-19 in this prospective cohort study. Clinical risk was assessed via National Early Warning Scores (NEWS) for each day of hospitalization. RESULTS: During hospitalization, 98% of patients had one or more procoagulable TEG result. Thromboelastography results remained prothrombotic upon discharge in 80% of patients. NEWS significantly decreased by discharge compared to the peak scores. CONCLUSIONS: Overall, patients were discharged from the hospital with significant clinical improvement, but without abnormal TEG results returning to a normal range. All patients in our study survived and few had thromboembolic events, so if and for how long these patients remain at risk for future complications warrants further investigation.


Subject(s)
COVID-19 , Thromboembolism , Thrombophilia , Adult , Blood Coagulation , Humans , Prospective Studies , Thrombelastography/adverse effects , Thrombelastography/methods , Thrombophilia/etiology
16.
PLoS One ; 17(1): e0262600, 2022.
Article in English | MEDLINE | ID: covidwho-1622369

ABSTRACT

In patients with severe forms of COVID-19, thromboelastometry has been reported to display a hypercoagulant pattern. However, an algorithm to differentiate severe COVID-19 patients from nonsevere patients and healthy controls based on thromboelastometry parameters has not been developed. Forty-one patients over 18 years of age with positive qRT-PCR for SARS-CoV-2 were classified according to the severity of the disease: nonsevere (NS, n = 20) or severe (S, n = 21). A healthy control (HC, n = 9) group was also examined. Blood samples from all participants were tested by extrinsic (EXTEM), intrinsic (INTEM), non-activated (NATEM) and functional assessment of fibrinogen (FIBTEM) assays of thromboelastometry. The thrombodynamic potential index (TPI) was also calculated. Severe COVID-19 patients exhibited a thromboelastometry profile with clear hypercoagulability, which was significantly different from the NS and HC groups. Nonsevere COVID-19 cases showed a trend to thrombotic pole. The NATEM test suggested that nonsevere and severe COVID-19 patients presented endogenous coagulation activation (reduced clotting time and clot formation time). TPI data were significantly different between the NS and S groups. The maximum clot firmness profile obtained by FIBTEM showed moderate/elevated accuracy to differentiate severe patients from NS and HC. A decision tree algorithm based on the FIBTEM-MCF profile was proposed to differentiate S from HC and NS. Thromboelastometric parameters are a useful tool to differentiate the coagulation profile of nonsevere and severe COVID-19 patients for therapeutic intervention purposes.


Subject(s)
Blood Coagulation , COVID-19/blood , Thrombelastography , Thrombophilia/blood , Adult , Aged , Algorithms , COVID-19/complications , COVID-19/diagnosis , Female , Humans , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Thrombophilia/diagnosis , Thrombophilia/etiology , Young Adult
17.
Front Immunol ; 12: 779453, 2021.
Article in English | MEDLINE | ID: covidwho-1566650

ABSTRACT

Introduction of vaccines against COVID-19 has provided the most promising chance to control the world-wide COVID-19 pandemic. However, the adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & Johnson [Ad26.CoV2.S] COVID-19 vaccines have been linked with serious thromboembolic events combined with thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT). The pathogenesis of COVID-19 VITT remain incompletely understood; especially the initial events that trigger platelet activation, platelet factor (PF)4 release, complex formation and PF4 antibody production are puzzling. This is a prospective study investigating the impact of different COVID-19 vaccines on inflammation (CRP, TNF-α, IL-1ß, IL-6, IL-8, IL-10), vascular endothelial activation (syndecan-1, thrombomodulin, E-selectin, ICAM-1, ICAM-3, VCAM-1), platelet activation (P-selectin, TGF-ß, sCD40L) and aggregation (Multiplate® impedance aggregometry), whole blood coagulation (ROTEM®), thrombin generation and PF4 antibodies to reveal potential differences between AZ and mRNA vaccines in individuals without VITT. The study included 80 (55 AZ and 55 mRNA) vaccinated individuals and 55 non-vaccinated age- and gender matched healthy controls. The main findings where that both vaccines enhanced inflammation and platelet activation, though AZ vaccination induced a more pronounced increase in several inflammatory and platelet activation markers compared to mRNA vaccination and that post-vaccination thrombin generation was higher following AZ vaccination compared to mRNA vaccination. No difference in neither the PF4 antibody level nor the proportion of individuals with positive PF4 antibodies were observed between the vaccine groups. This is the first study to report enhanced inflammation, platelet activation and thrombin generation following AZ vaccination compared to mRNA vaccination in a head-to-head comparison. We speculate that specific components of the AZ adenovirus vector may serve as initial trigger(s) of (hyper)inflammation, platelet activation and thrombin generation, potentially lowering the threshold for a cascade of events that both trigger complications related to excessive inflammation, platelet and coagulation activation as observed in epidemiological studies and promote development of VITT when combined with high-titer functionally active PF4 antibodies.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Inflammation/blood , Platelet Activation , SARS-CoV-2/immunology , Adult , Blood Coagulation , C-Reactive Protein/analysis , Cytokines/blood , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Platelet Factor 4/immunology , Thrombelastography , Thrombin/metabolism , Thrombocytopenia , Thrombosis
18.
Adv Med Sci ; 67(1): 39-44, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1562003

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition associated with coagulopathy which may result in severe thromboembolic complications. Cardiac injury is not uncommon in hospitalized COVID-19 patients and therefore we aimed to investigate whether it stems from an abnormal coagulative state. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study on consecutive patients hospitalized due to COVID-19. Traditional coagulation and whole blood rotational thromboelastometry tests were compared between patients with and without cardiac injury. Cardiac injury was defined by increased levels of high-sensitivity cardiac troponin I (hs-cTnI). RESULTS: The study population consisted of 104 patients (67% males, median age 65 years), of whom 40 (38%) developed cardiac injury. No clinical differences in the traditional coagulation parameters were observed between patients with and without cardiac injury. Thromboelastometry analysis revealed abnormal maximum clot firmness (MCF) levels in FIBTEM assay in 80 (77%) patients. No significant differences in MCF values (p â€‹= â€‹0.450) and percentage of abnormal MCF (p â€‹= â€‹0.290) were detected between patients with and without cardiac injury. Cardiac injury - not hypercoagulability - was associated with mortality (p â€‹= â€‹0.016). CONCLUSIONS: No differences in traditional coagulation and rotational thromboelastometry parameters were found among hospitalized COVID-19 patients with and without cardiac injury. Other mechanisms besides hypercoagulability may be a main culprit for cardiac injury in COVID-19 patients.


Subject(s)
COVID-19 , Aged , COVID-19/complications , Cross-Sectional Studies , Female , Humans , Male , Retrospective Studies , SARS-CoV-2 , Thrombelastography
19.
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 , Black or African American/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 , White People/statistics & numerical data
20.
Turk J Med Sci ; 52(1): 1-10, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1515564

ABSTRACT

BACKGROUND: A high D-dimer level may indicate the risk of coagulopathy and mortality in COVID-19 patients. T hromboelastography (TEG) is a test that evaluates clot formation and fibrinolysis in real-time, unlike routine coagulation tests. The study aimed to investigate the coagulation process with TEG in patients diagnosed with COVID-19. METHODS: The study was performed at our university hospital, chest diseases outpatient clinic as a cross-section study. A total of 51 patients with 23 high D-dimer levels group (HDG) and 28 low D-dimers group (LDG) were included in the study. TEG analysis was performed at the pretreatment evaluation in these two groups. RESULTS: D-dimer and fibrinogen levels of the HDG were higher than those of the LDG (550 vs. 90 ng/mL, p < 0.001; 521 vs. 269 mg/ dL, p < 0.001, respectively). In TEG analysis, HDG's R and K values were lower than LDG, and HDG's Angle, MA, and CI values were higher than LDG (p = 0.037; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). ROC curve analysis suggested that the optimum TEG parameters cut-off points for thrombosis risk were as below: for K was ≤2.1 min, for R was ≤6.1 min, for Angle was >62°, MA was 60.4 mm.


Subject(s)
COVID-19 , Thrombelastography , Humans , COVID-19/diagnosis , Blood Coagulation , Blood Coagulation Tests
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