Thrombotic events that frequently occur in COVID-19 are predominantly venous thromboemboli (VTE) and are associated with increasing disease severity and worse clinical outcomes. Distinctive microvascular abnormalities in COVID-19 include endothelial inflammation, disruption of intercellular junctions and microthrombi formation. A distinct COVID-19-associated coagulopathy along with increased cytokines and activation of platelets, endothelium and complement occur in COVID-19, which is more frequent with worsening disease severity. This proinflammatory milieu may result in immunothrombosis, a host defence mechanism that can become dysregulated, leading to excess formation of immunologically mediated thrombi which predominantly affect the microvasculature. The haemostatic and immune systems are intricately linked, and multifactorial processes are likely to contribute to VTE and immunothrombosis in COVID-19. This state-of-the-art review will explore the pathobiological mechanisms of immunothrombosis and VTE in COVID-19 focusing on: COVID-19-associated coagulopathy, pathology, endothelial dysfunction and haemostasis, the immune system and thrombosis, genetic associations and additional thrombotic mechanisms. An understanding of the complex interplay between these processes is necessary for developing and assessing how new treatments affect VTE and immunothrombosis in COVID-19.

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Background Adjuvant chemotherapy (AC) improves survival after pancreatoduodenectomy (PD) for periampullary cancer. Unfortunately, not all PD patients are fit for AC, and it is likely that perioperative malnutrition plays a role. Therefore, the aim of this study was to investigate the relationship between early postoperative anthropometric and nutritional measures with fitness for adjuvant chemotherapy after PD. Methods All patients undergoing PD for periampullary cancer between 2018–2020 at our institution were reviewed. Those who were referred for AC were included in the study and split into two groups: those who received AC and those who were not fit enough to receive AC. Demographic, perioperative, anthropometric, nutritional and outcome measures were compared between the two groups. Results 66 patients were suitable for inclusion in the study, of which 15 (23%) were not fit for AC. Overall survival was significantly greater in the AC group (29.7 months vs. 16.7 months; p=0.037). Body mass index (BMI) was similar between the groups at admission but during inpatient stay dropped significantly more in the no-AC group (-1.34 kg/m2 vs. -0.10 kg/m2; p=0.035). BMI was also significantly lower at first follow-up (3–4 weeks after surgery) in the no-AC group (20.2 kg/m2 vs. 25.2 kg/m2; p=0.018). Albumin was similar between the two groups on admission and discharge. However, at first follow-up albumin was significantly lower in the no-AC group (31 g/L vs. 38 g/L; p=0.019). There was no difference in postoperative complications between the two groups. Conclusions BMI and albumin in the early postoperative period appear to be significantly related to fitness for adjuvant chemotherapy. By routinely measuring these values and intervening in those struggling with nutrition postoperatively before their first Oncology appointment, it may be possible to increase the proportion of patients fit enough to receive AC, and thus improve survival after PD. BMI and albumin have some limitations so future work should concentrate on more reliable measures such as body composition measures.