The Evaluation of Hemostasis by Thromboelastography, Platelet Function Testing, and Biomarker Analysis in Hospitalized COVID-19 Patients
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Frequency of Hypercoagulability as measured by thromboelastography measured by TEG and platelet aggregation.
研究概览
简要总结
Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to thrombotic diseases (venous and arterial) with reported rates in hospitalized patients between 17-40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and stasis. The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage point to a significant hypercoagulable state. The latter induces a high risk for micro-thrombi and multi-organ ischemia. Therefore, early detection and a comprehensive understanding of the influence of the virus on the coagulation and platelet pathways are essential to address this epidemic. It is critical at this time to make all efforts possible to optimize our available technology to care for COVID-19 patients who are at risk for thrombotic disease through appropriate choice, dosing, and laboratory monitoring of antithrombotic therapy.
The investigators hypothesize that COVID-19 is a heightened prothrombotic/hypercoagulability state that can be characterized using platelet function testing and thrombelastography. More information is required to study the effect of COVID-19 on coagulation and platelet pathways to develop effective antithrombotic treatment strategies.
This is a multi-center center, non-interventional study enrolling patients who are COVID-19 positive or who have tested negative showing indication of the disease (high D-dimer and positive lung imaging). The study specific laboratory assessments will be obtained at baseline (closest to time of hospitalization), Day 3, and Day 8 from baseline and at hospital discharge. Laboratory measurements for TEG 6S , platelet aggregation, T-TAS, urinary thromboxane, genotyping, serum and plasma biomarkers will be analyzed . In-hospital and clinical follow-up data will be entered into a COVID registry Patients will be followed for clinical events during hospitalization, and up to 6 months after discharge.
Patients (n=100) hospitalized with at least one of the following will be enrolled.
- With a confirmed diagnosis of COVID-19 infection using a positive RT- PCR or a positive IgG antibody test prior to or during hospitalization or
- With a negative COVID-19 RT-PCR test but with symptoms of possible
COVID-19 infection and:
- an elevated D-dimer and/or
- positive imaging results showing unilateral or bilateral pneumonia or ground-glass opacity in lungs.
详细描述
The investigators hypothesize that serial evaluation of (a) intrinsic thrombogenicity measured by thromboelastography (b) platelet activation and aggregation, and (c) selected biomarkers will provide the "blueprint" of individual hemostasis to precisely characterize COVID-19 patients who are at heightened risk for thrombosis or bleeding. The latter will facilitate future efforts to personalize antithrombotic therapy regimens in COVID-19 patients.
Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to predispose patients to thrombotic diseases (venous and arterial) with reported rates in hospitalized patients between 17- 40%. The influence of SARS-CoV-2 infection on the coagulation is hypothesized to be regulated by platelet activation, proinflammatory cytokines, endothelial cell injury and stasis.
The elevated levels of d-dimer and fibrinogen and clinical signs of organ damage point to a significant hypercoagulable state. The latter induces a high risk for micro-thrombi and multiorgan ischemia. Therefore, early detection and a comprehensive understanding of the influence of the virus on the coagulation and platelet pathways are essential to address this epidemic. It is critical at this time to make all efforts possible to optimize our available technology to care for COVID-19 patients who are at risk for thrombotic disease through appropriate choice, dosing, and laboratory monitoring of antithrombotic therapy.
Our research group and others have reported a "thrombo-inflammatory" state-a distinct pathophysiological state -of heightened platelet function, hypercoagulability, and inflammation in several cardiovascular disease (CVD) processes. It has been demonstrated that patients with acute respiratory infections are at elevated risk for acute myocardial infarction after influenza (incidence ratio [IR] 6.1, 95% CI 3.9-9.5) and after non-influenza viral illnesses including other coronavirus species (IR 2.8, 95% CI 1.2-6.2). Tantry et al. proposed a mechanistic link between inflammation and heightened thrombogenicity in the presence of unstable CVD state. Furthermore, investigators have hypothesized that this thrombo-inflammatory state becomes even more relevant when patients with CVD and human immunodeficiency virus (HIV) infection undergo percutaneous coronary intervention (PCI).A similar scenario may be present during COVID-19 infection, where evidence of an early myonecrosis may be related to fundamental changes in pathways affecting thrombosis. However, currently, there is no information on how COVID-19 influences hemostasis/thrombosis pathways and subsequent adverse clinical event occurrences.
Cardiovascular comorbidities including hypertension, obesity, high cholesterol, and diabetes mellitus are common in patients with COVID-19 and such patients are at higher risk for morbidity and mortality.12 Furthermore, emerging demographic data in COVID-19 patients shows that incidence and mortality is disproportionately higher in African Americans and Latinos. In a study conducted at Sinai hospital, Lev et al. analyzed a large cohort of racially diverse patients (n=1,172) with CAD or CV risk and demonstrated that sex and race are significantly associated with platelet-fibrin clot strength, a marker of hypercoagulability. Most interesting, AA women had the highest thrombogenicity profile, potentially conferring a highrisk phenotype for thrombotic event occurrence. Furthermore, in a study entitled, "PlateletReactivity in Different Ethnicities" also conducted at Sinai hospital, investigators have demonstrated that Latino and AA races had the highest platelet-fibrin clot strength as compared to Caucasians and others races studied.The latter findings may be described by difference in frequency of a single-nucleotide variant in protease-activated receptor-4 (PAR-4) between AA and Caucasians respectively (63% vs 19%). PAR-4 is an active thrombin receptor on human platelets essential for thrombin-induced platelet activation and has been shown to be more active in African Americans as compared to Caucasians. This evidence may provide a potential mechanistic explanation for racial disparities observed in COVID-19 patients and require further investigation. Hence, investigators will collect a genetic sample to analyze single-nucleotide variant of PAR-4 and other genetic markers related to thrombosis.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •· Confirmed diagnosis of COVID-19 infection using a positive RT-PCR or a positive IgG antibody test prior to or during hospitalization or,
- •· With a negative COVID-19 RT-PCR test but with symptoms of possible COVID-19 infection and:
- •elevated D-dimer and/or
- •positive imaging results showing unilateral or bilateral pneumonia or ground-glass opacity in lungs · The subject or legal authorized representative able to read and sign an informed consent document including authorization permitting release of personal health information approved by the investigator's Institutional Review Board (IRB).
排除标准
- •Subjects will be excluded from entry if ANY of the criteria listed below are met:
- •Less than 3 years of age
- •Subject is pregnant
- •Active treatment for cancer
- •History of long-term use of immunosuppressive agents
- •History of severe chronic respiratory disease and requirement for long-term oxygen therapy
- •Patients undergoing hemodialysis or peritoneal dialysis
- •Patients on full dose anticoagulant at the time of enrollment
- •Any condition unsuitable for the study as determined by investigators
结局指标
主要结局
Frequency of Hypercoagulability as measured by thromboelastography measured by TEG and platelet aggregation.
时间窗: up to day 8
Frequency of Hypercoagulability as measured by point-of-care thromboelastography (TEG6s)
次要结局
- Frequency of High Platelet Reactivity (HPR)(up to day 8)
- Frequency of thrombo-inflammatory syndrome(up to day 8)
- Correlation between HPR and clinical outcomes(through study completion, an average of 6 months)
- Determine level of platelet aggregation(up to day 8)
- Determine platelet thrombi and fibrin rich platelet thrombus Area Under the Curve(up to day 8)
- Correlation between TEG6s parameters and clinical outcomes(through study completion, an average of 6 months)
- Determine response to anticoagulation therapy(up to day 8)
- Determine short and long IgG, IgM and IgG antibody levels(up to day 6 months)