Thrombogenicity in Acute Exacerbation of COPD
Research type
Research Study
Full title
Fractal Dimension as a Biomarker of Thrombogenicity in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)
IRAS ID
216266
Contact name
P A Evans
Contact email
Duration of Study in the UK
5 years, 11 months, 30 days
Research summary
Chronic obstructive pulmonary disease (COPD) is characterised by non-reversible airflow obstruction to the lungs caused by chronic bronchitis and emphysema. About one million people suffer from COPD in the United Kingdom and there are approximately 25,000 deaths every year as a consequence. The predominant cause of COPD is cigarettes smoking. COPD costs National Health Service (NHS) nearly £800 million annually. People who suffer from COPD have two to four times increased mortality from ischaemic heart disease and one fourth of patients develop blood clot in the lungs (pulmonary embolism) particularly during acute exacerbations. This may be due to an increased systemic inflammatory response, dehydration and immobility. Conventional biomarkers of coagulation have been proved to be ineffective in quantifying the thrombotic risk in a number of diseases such as cancer, stroke and myocardial infarction. Fractal dimension (df) is a new biomarker of coagulation that has been shown to quantify the global pathological effects of abnormalities of coagulation and thrombolysis on clot microstructure. The aim of the study is to demonstrate whether the tendency of blood clot formation differs between patients with stable COPD and healthy individuals and between stable COPD patients and patients with acute exacerbation of COPD (AECOPD). Patients aged 35 and above with a confirmed diagnosis of COPD as defined by GOLD criteria (Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016) will be recruited to the study. The study will be conducted in Haemostasis Biomedical Research Unit (HBRU), Morriston hospital. The study aims to recruit approximately 150-200 patients. Blood samples will be taken from the participants and the thrombogenicity will be assessed using the conventional biomarkers and the new biomarker fractal dimension (df). [COVID 19 amendment 20/05/2020] COVID19 SUB STUDY\n1. Include a new arm for Covid-19 patients. We aim to investigate disease progression in COVID 19 and its effect on using markers of clot microstructure: This will be an observational study that aims to investigate the hypothesis that clot microstructural analysis as determined by df can act as a significant predictor of mortality and thrombogenicity in patients with SARS-CoV-2 infection being mechanically ventilated. We will plan to recruit 80 patients over the 12\nmonth duration of the project. Relationship between df and other standard markers of thrombogenicity in COVID 19:\nWe will also determine and quantify using df how the extent of the inflammatory response alters coagulation and impacts on clinical outcome as determined by their global effect on the development of abnormal clot strength and microstructure. As we wish to use multiregression analysis we will limit the number of variables we regress to the total number of subjects assuming at least 10 subjects are required for each variable (meaning we will regress with\n8 variables if we are able to recruit 80 subjects).\n2. ROTEM (Rotational Thromboelastometry): provides a rapid assessment of clot development from secondary\nhemostasis to clot lysis by evaluating clot formation, clot firmness, and clot fibrinolysis.ROTEM reflect clot volume and mass and the general perception is that if the clot volume and mass is high, then the clot strength is high, however some studies show that this is not the case in other inflammatory disease. To carry out ROTEM 1.5mls of blood is required that can be taken from the remaining citrate blood sample after testing clot contraction.\n3. Anti-Xa levels: The anti–factor Xa assay is designed to measure plasma heparin (unfractionated heparin [UH] and low molecular weight heparin [LMWH]) levels and to monitor anticoagulant therapy. AECOPD patients who get admitted to the hospital receives a prophylactic dose of Tinzaparin/ Clexane either in Emergency Department or in the ward. This is relatively a small dose and is not known to alter the clotting tests such as PT, APTT and Fibrinogen\nlevels. However, there is no evidence till date to suggest that prophylactic dose of Tinzaparin/ Clexanealters clot microstructure. The reason for doing this test is to evaluate the effect on mechanical clot properties. This can be added to the citrate blood sample send for testing coagulation screen (PT, APTT, Fibrinogen).\n
REC name
Wales REC 6
REC reference
17/WA/0123
Date of REC Opinion
26 Jun 2017
REC opinion
Further Information Favourable Opinion