Objectives Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. Methods A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. Results A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0–200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5–11] vs. 6 [5–8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04–2.5), p = 0.034). Conclusion Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival.
Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. Methods Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. Results Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. Conclusion Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.
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