A Feasibility Study Evaluating the Prognostic and Logistic Value of Measuring D-dimer Levels in Primary Care Using (POC) Tests.

The diagnosis of conditions that cause hypercoagulability result in economic burden for the healthcare industry. The non-specific symptoms incur clinical problems for diagnosing conditions such as Deep Vein Thrombosis (DVT). DVT is a common condition in the UK, with more than 140,000 patients presenting to primary care with suggestive symptoms each year (Thrombosis UK, 2020). The reduction of blood flow caused by a blood clot in a deep set vein can lead to a pulmonary embolism and infarcts throughout the circulation, which is potentially fatal if not treated quickly.

The purpose of this study would therefore be to safely exclude DVT in a primary care setting using Point of Care (POC) testing as a means of reducing the number of referrals to secondary and tertiary care. The use of a small protein fragment as a biomarker utilising POC testing will be investigated to determine the clinical effectiveness and accuracy of ruling out DVT in primary care. The current practise however relies on referral from a primary care setting of all patients with symptoms of hyper coagulation, for diagnostic testing with ultrasonography and laboratory generated D-Dimer analysis at secondary care. Although ultrasonography is safe and easily available, it requires an additional patient visit and increases the need for clinical and diagnostic resources. The use of a D-dimer POC test could therefore be used to exclude a DVT at the initial presentation in the primary setting and reduce the economic burden on the NHS and be more convenient for the patient.

Venous Thromboembolism (VTE) encompasses the conditions deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE is the third most frequent cardiovascular disease globally and can be lethal in the acute phase and potentially lead to a chronic disease and disability. The potential to prevent a chronic disease from developing however is highly possible with the use of a rapid and reliable diagnosis. Only around 15% of patients with suspected DVT will have a confirmed ultrasonography scan, with an annual incidence of 1 per 1000 (Wells, Anderson and Rodger, 2004). Using ultrasonography to diagnose DVT is reliable, although currently the only recognised method post initial assessment. A more precise diagnosis at primary care can reduce a large percentage of ultrasound referrals to secondary care with an advantage to both patients, clinical staff and efficiencies within the health care service, keeping patients and their care in the primary care setting.

D-dimer is a small protein fragment that is the result of endogenous fibrinolysis and can be found in healthy individuals in negligible amounts of around 100-200ng/ml (Lippi, Bonfanti, Saccenti and Cervellin, 2014). D -dimer can be detected using monoclonal antibody immunoassay based lab methods as the current method in practice. Current problems faced using D-dimer as a diagnostic biomarker are that it is highly non-specific. D-dimer levels may rise in conjunction with many other conditions such as cellulitis, inflammation, liver conditions and in pregnancy (Wells, Anderson and Rodger, 2004). D-dimer therefore cannot solely be used to diagnose a venous thromboembolism (VTE), further imaging testing (ultrasonography) would likely be needed to confirm or exclude. However, a negative test is useful as it is allows clinicians to reliably exclude VTE on the basis that clinical probability is low (Lippi, Bonfanti, Saccenti and Cervellin, 2014). Clinical probability has been generated for DVT using a points scoring 'decision rule' to categorise risk variables in order to reduce referrals to secondary care for a D-dimer laboratory test.

The two main points scoring rule systems currently in place are the Wells Rule and Primary Care Rule. The Wells Rule combines patient history and a physical examination which is followed by a D-dimer assay to determine patients for ultrasonography. Clinicians are able to risk stratify patients of a low risk score (Wells Score <2) and a negative D-dimer to be excluded from ultrasonography (van der Velde et al., 2011). A 2006 study concluded that patients with a low clinical probability have prevalence of DVT >5%, suggesting the Wells Rule is capable of categorising patients with low, moderate and high probability (Plüddemann et al., 2012). However, the Wells Rule has been criticised for its inaccuracies with prevalence of thrombosis in as many as 2.9% of patients in primary care and with a normal D-dimer (Antovic et al., 2012).