Thromboelastometry demonstrates endogenous coagulation activation in nonsevere and severe COVID-19 patients and has applicability as a decision algorithm for intervention.

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.

Hemostatic System (Fibrinogen Level, D-Dimer, and FDP) in Severe and Non-Severe Patients With COVID-19: A Systematic Review and Meta-Analysis.

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

How to recognize and manage COVID-19-associated coagulopathy.

COVID-19 is frequently associated with abnormalities on coagulation testing and a coagulopathy driven by inflammation, intravascular coagulation activation, and microvascular thrombosis. Elevated D-dimer is the most common finding and is a predictor of adverse outcomes including thrombosis, critical illness, and death. Although COVID-19-associated coagulopathy has some similarities to disseminated intravascular coagulation, the platelet count is usually preserved, coagulation times are usually normal or minimally prolonged, and thrombosis is more common than bleeding, at least in noncritically ill patients. Bleeding is uncommon but may be a significant problem in critically ill patients, including those who may develop a consumptive coagulopathy with frank disseminated intravascular coagulation and those on extracorporeal membrane oxygenation. Blood product support to correct coagulopathy is reserved for bleeding patients or those requiring invasive procedures. Current recommendations suggest that all hospitalized patients should receive at least a prophylactic dose of anticoagulation. Results from a multiplatform randomized clinical trial suggest that therapeutically dosed anticoagulation may improve outcomes, including the need for organ support and mortality in moderately ill patients but not in those requiring critical care. The results of ongoing trials evaluating the impact of different antithrombotic strategies (therapeutic agents and intensity) on COVID-19 outcomes are eagerly awaited and are expected to have important implications for patient management. We also discuss COVID-19 vaccine-associated cytopenias and bleeding as well as vaccine-induced thrombotic thrombocytopenia, in which thrombosis is associated with thrombocytopenia, elevated D-dimer, and, frequently, hypofibrinogenemia.

Relationship between serum soluble endothelial protein C receptor level and COVID-19 findings.

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

Thrombogenicity markers for early diagnosis and prognosis in COVID-19: a change from the current paradigm?

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.

D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies.

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

COVID-19 and Its Implications for Thrombosis and Anticoagulation.

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

D-dimer Level and Diabetes in the COVID-19 Infection.

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

COVID-19 and aortic disease: a practical systematic review of the literature on management and outcomes.

INTRODUCTION: Since the outbreak of the 2019 coronavirus (COVID-19), vascular specialists have faced dramatic changes in clinical and surgical practice. Although COVID-19 pulmonary signs and symptoms were the most pertinent problems initially, in the long term, cardiovascular complications became the most fearsome, with poor outcomes in terms of morbidity and mortality. Algorithms and decision-making procedures have been modified, not only to treat new clinical findings in COVID-19 positive patients, but also to avoid complications related to pulmonary and systemic infections. Additionally, COVID-19-negative patients experienced challenging management, due to hospital crowding, the risk of nosocomial COVID-19 transmission, and pandemic emergencies. In this context, aortic interventions were subject to several difficulties. First, in COVID-19-positive patients, there was the onset of new pathological scenarios including thrombotic manifestations and the subsequent complications. Second, in both COVID-19-negative and positive patients, there was a need to deliver optimal treatment with acceptable perioperative risks, forcing a rethinking of decision-making especially in terms of indications for treatments. The aim of this systematic review is to present evidence published on COVID-19 and aortic-related issues, highlighting some challenging aspects regarding management, treatment and outcomes. EVIDENCE ACQUISITION: Data search was performed on PubMed, Scopus and Web of Science, using as time range "January 1st, 2000 - May 1st, 2021." Only articles in English language were included. Key words used for the query were "Aorta" AND "COVID-19" OR "SARS-CoV-2." Furthermore, the NCBI database of "SARS-CoV-2 Resources" was interrogated to find further relevant studies. EVIDENCE SYNTHESIS: The search retrieved 416 papers; among these, 46 studies were eligible and reviewed in depth. The published literature suggests the existence of a hypercoagulable state in patients with COVID-19 disease occurring via direct and indirect mechanisms. COVID-19 infection seems to promote a prothrombotic status that aggravates vascular disease. Regardless of clinical laboratory or status, active COVID-19 infection is considered a risk factor for poor vascular surgery outcomes. Specifically, it is associated with a fourfold increased risk of death and a threefold increased risk of major adverse events. Prognosis of patients hospitalized with COVID-19 disease is often determined by the extent of pulmonary disease, although vascular complications also greatly affect outcomes. Nevertheless, although COVID­19 is highly morbid, in high­risk operations good outcomes can still be achieved even in elderly patients with COVID­19. CONCLUSIONS: In the case of aortic disease during active COVID-19 infection, poor outcomes are associated with COVID-19 vascular and non-vascular complications, while for COVID-19-negative patients not much changed in terms of outcomes, despite the difficulties in management. Endovascular repair, when possible, minimized the impact of treatment, reducing the risk of COVID-related postoperative complications or acquired infection in negative patients.

COVID-19 and acute limb ischemia: a systematic review.

INTRODUCTION: The main goal of this systematic review was to analyze the outcomes of acute limb ischemia (ALI) in patients suffering from the novel Coronavirus: COVID-19 (SARS-CoV-2). EVIDENCE ACQUISITION: A systematic review on Medline and Embase was conducted up to May 15, 2021. All papers were sorted by abstract and full text by two independent authors. Systematic reviews, commentaries, and studies that did not distinguish status of COVID-19 infection were excluded from review. Patient demographics were recorded along with modality of treatment (endovascular and/or surgical). We analyzed 30-day outcomes, including mortality. Primary outcome was to evaluate clinical characteristic of ALI in patients affected by SARS-CoV-2 in term of location of ischemia, treatment options and 30-day outcomes. EVINDENCE SYNTHESIS: We selected 36 articles with a total of 194 patients. Most patients were male (80%) with a median age of 60 years old. The treatment most used was thromboembolectomy (31% of all surgical interventions). A total of 32 patients (19%) were not submitted to revascularization due to critical status. The rate of technical success was low (68%), and mortality rate was high (35%). CONCLUSIONS: This review confirms that SARS-CoV-2 is associated with a high risk of ALI. Further studies are needed to investigate the association and elucidate potential mechanisms, which may include a hypercoagulable state and hyperactivation of the immune response. Furthermore, management of ALI is not standardized and depends on patient condition and extension of the thrombosed segment. ALI in COVID-19 patients is associated with high risk of failure of revascularization and perioperative mortality.

Coagulation profiles and viscoelastic testing in multisystem inflammatory syndrome in children.

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

Association of coagulation disturbances with severity of COVID-19: a longitudinal study.

OBJECTIVES: Coagulation dysfunction is an evident factor in the clinical diagnosis and treatment of patients with coronavirus disease 2019 (COVID-19), appearing even in COVID-19 patients with normal inflammation indices. Therefore, this study aimed to analyze the characteristics of coagulation function indices in COVID-19 patients to investigate possible mechanisms through the comparison of non-severe and severe COVID-19 patients. METHODS: We included 143 patients whose clinical characteristics, coagulation function, and other indices such as inflammatory factors were collected and compared based on disease severity. RESULTS: Activated partial thromboplastin time (APTT), D-dimer, and fibrinogen levels were evidently higher in the severe group than in the non-severe group. Among non-severe COVID-19 patients, the aforementioned indicators depicted increasing trends, but the fibrinogen level alone was higher than normal. However, in severe COVID-19 patients, values of all three indices were higher than normal. In severe COVID-19 patients, fibrinogen and D-dimer were correlated with several inflammation indices during the early stage of the disease. However, no correlation between fibrinogen and inflammatory factors was observed in non-severe COVID-19 patients at any time point. DISCUSSION: Results revealed that the hypercoagulability tendency of severe COVID-19 patients was more evident. The relationship between coagulation function and inflammatory factors showed that changes in coagulation function in severe COVID-19 patients may be related to abnormal increase in inflammatory factors at an early stage; however, in non-severe COVID-19 patients, there might be other factors leading to abnormal coagulation. CONCLUSION: Inflammatory factors were not the only cause of abnormal coagulation function in COVID-19 patients.

In vitro diagnostics for the medical dermatologist. Part II: Hypercoagulability tests.

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.

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression.

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.

Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study.

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

COVID-19-related laboratory coagulation findings.

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.

Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis.

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.

Fibrinolysis Shutdown and Thrombosis in a COVID-19 ICU.

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.

Rotational Thromboelastometry Reveals Distinct Coagulation Profiles for Patients With COVID-19 Depending on Disease Severity.

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.