RESUMEN
Background/Objective: Cushing syndrome (CS) is a prothrombotic state associated with an increased risk of postoperative venous thrombosis. We aim to present the case of a patient with Cushing disease who underwent pituitary surgery and subsequently developed acute lower extremity deep venous thromboses after anticoagulation was stopped. Case Report: We present the case of a 57-year-old woman who was admitted for intra-abdominal abscesses after a gastric bypass surgery and was found to have evidence of severe CS. Her 24-hour urinary free cortisol level was 898.6 µg/24 h. She was diagnosed with Cushing disease and underwent transsphenoidal resection of a pituitary adenoma, with an appropriate postoperative drop in the cortisol level. She received thromboprophylaxis during hospitalization; however, this was discontinued upon discharge, on postoperative day 9, because she was ambulating. Five days after hospital discharge and 14 days after her surgery, she developed left lower extremity edema and was found to have 4 deep venous thromboses. Discussion: As previously described, thrombotic risk can be elevated for at least 1 month after surgery for CS, and thromboprophylaxis can decrease this risk. Conclusion: This case highlights the need for clear recommendations for the duration of postoperative thromboprophylaxis in patients with CS. Clinicians should consider continuing thromboprophylaxis for at least 1 month after surgery for CS.
RESUMEN
COVID-19 is characterized by vascular inflammation and thrombosis, including elevations in P-selectin, a mediator of inflammation released by endothelial cells. We tested the effect of P-selectin inhibition on biomarkers of thrombosis and inflammation in patients with COVID-19. Hospitalized patients with moderate COVID-19 were randomly assigned to receive either placebo or crizanlizumab, a P-selectin inhibitor, in a double-blind fashion. Crizanlizumab reduced P-selectin levels by 89%. Crizanlizumab increased D-dimer levels by 77% and decreased prothrombin fragment. There were no significant differences between crizanlizumab and placebo for clinical endpoints. Crizanlizumab was well tolerated. Crizanlizumab may induce thrombolysis in the setting of COVID-19. (Crizanlizumab for Treating COVID-19 Vasculopathy [CRITICAL]; NCT04435184).
RESUMEN
Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin-antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.