Coagulopathy (Tang, et al 2020) and a prothrombotic diathesis with high D-dimer and fibrinogen levels (Al-Samkari, et al 2020) are associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Extensive thrombosis in small vessels and the microvasculature in lungs and extrapulmonary organs has been confirmed histologically (Zhang, et al 2020). Early studies showed that the venous thromboembolism (VTE) incidence in hospitalised COVID-19 patients can be as high as 25% (Songping, et al 2020), and more recent studies have indicated this can be expanded to other macrovascular thrombotic complications, such as a higher than expected prevalence of pulmonary emboli in patients with COVID-19 (Klok, et al 2020, Stoneham, et al). The term “diffuse pulmonary intravascular coagulopathy” has been proposed to describe the lung-restricted vascular immunopathology associated with COVID-19. This is distinct from disseminated intravascular coagulation in its early stages and is characterised by increased D-dimer with normal platelet count and normal/elevated fibrinogen (McGonagle, et al 2020). Increased VTE rate has been associated with higher D-dimer level, and in the same study, an association between VTE and death was found (Middeldorp, et al 2020). Another study has shown a D-dimer greater than 1 µg/mL was associated with a poorer prognosis (Zhou, et al 2020). Patients requiring mechanical ventilation who were treated with therapeutic anticoagulation had an in-hospital mortality of 29.1% compared to 62.7% in patients who did not receive anticoagulation. Longer duration of anticoagulation was associated with a reduced risk of mortality (Paranjpe, et al 2020).
Funding
Mining the Wnt signalling-responsive surfaceome for drug targets in acute myeloid leukaemia; G3090; WELLCOME TRUST
How does SARS CoV-2 infect blood vessels?; G3146; UK RESEARCH AND INNOVATION; MR/V036750/1
Modelling and targeting Acute Myeloid Leukaemia cells in the Bone Marrow protective niche; G3106; SUSSEX CANCER FUND FOR TREATMENT AND RESEARCH
Drug-induced selective lethality in populations of DNMT3A knockdown cells; G2782; WELLCOME TRUST; 218435/Z/19/Z
In vitro modelling and therapeutic targeting of tumour cell migration in chronic lymphocytic leukaemia.; G2544; BLOODWISE