Venous thromboembolism (VTE), comprising both pulmonary embolism (PE) and deep vein thromboses (DVT) is a common, multi-causal disease with serious short and long-term complications. VTE also emerged as a common and life-threatening complication of COVID-19.
VTE diagnosis is challenging, as the predisposing common risk factors and clinical presentation can be consistent with multiple other conditions, particularly in the case of PE. Current VTE diagnostic work-up includes assessment of clinical probability, using clinical decision rules, e.g., the Well’s score, in combination with elevated plasma D-dimer levels. However, D-dimer, a clot breakdown product, can be elevated in several other non-VTE conditions such as inflammation, surgery, and cancer. In medium and high probability cases, diagnostic imaging, i.e., compression ultrasound (CUS) on suspicion of DVT, or computed tomography pulmonary angiogram (CTPA) on suspicion of PE, is necessary to exclude or confirm the diagnosis. Thus, specific biomarker-based tools in the diagnostic workup are the need of the hour which could reduce unnecessary imaging, save resources and, in the case of CTPA, reduce exposure to radiation and contrast agents. Thus, researchers attempted to identify novel biomarkers such as complement factor H-related protein 5 (CFHR5) association with acute VTE with a potential link to underlying VTE pathogenesis.
Using GWAS analysis of 2967 individuals, a genome-wide significant pQTL signal on chr1q31.3 was found to be associated with CFHR5 levels. It was observed that higher CFHR5 levels are associated with increased thrombin generation in patient plasma and that recombinant CFHR5 enhances platelet activation in vitro. Moreover, in hospitalised patients with COVID-19, CFHR5 levels at baseline were associated with a short-time prognosis of disease severity, defined as the maximum level of respiratory support needed during the hospital stay. The results indicated a clinically important role of the regulation of the alternative pathway of complement activation in the pathogenesis of VTE and pulmonary complications in acute COVID-19. Thus, CFHR5 is a potential diagnostic and/or risk predictive plasma biomarker reflecting underlying pathology in VTE and acute COVID-19.
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