RESUMEN
Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil activation. Hyper-adhesive VWF may promote VOC in sickle cell disease. SUMMARY: Background Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vaso-occlusion is unclear. Objectives To longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13 during vaso-occlusive crisis (VOC). Methods In this observational study, we obtained sequential blood samples in adult SCD patients during VOC. Results VWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib-binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF:pp) and ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF:pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS-13 activity was lower, than in patients without this complication. Conclusions We provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS-13 deficiency. This hyper-reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD.
Asunto(s)
Proteína ADAMTS13/sangre , Anemia de Células Falciformes/sangre , Enfermedades Vasculares/sangre , Factor de von Willebrand/metabolismo , Enfermedad Aguda , Adulto , Adhesión Celular , Células Endoteliales/citología , Femenino , Humanos , Inflamación , Masculino , Microcirculación , Neutrófilos/metabolismo , Estrés Oxidativo , Dolor , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Door-to-needle time (DNT), defined as the time between arrival at the emergency department (ED) and intravenous (iv) antibiotic administration is of crucial importance in the treatment of patients suffering from serious infections. The aim of this project was to reduce the DNT for patients with a serious infection as primary outcome parameter. METHODS: All adult patients arriving at the ED with a suspected infection for whom admission and iv antibiotics were indicated were included. RESULTS: Firstly, baseline DNT was measured and potential delaying factors were identified. Subsequently, five tailored interventions were implemented at regular intervals and their effects on the DNT were analysed. The interventions were: 1) additional resident attendance during peak hours, 2) immediate examination by residents prior to laboratory results, 3) chest X-ray at the ED instead of the external radiology department, 4) iv antibiotic administration at the ED instead of the ward and finally, 5) primary dipstick urine analysis at the ED. A total of 295 patients were included (53.9% men), median age was 59 years (IQR 46 to 73). Median baseline DNT was 183 min (IQR 122 to 296). Implementation of the first three interventions did not reduce the DNT ; however, after implementation of the fourth (administer all antibiotics at the ED) and finally all five interventions the DNT was reduced by 15.3% (p=0.040) to a final median DNT of 155 min (IQR 95 to 221). CONCLUSION: Identification of delaying factors and implementation of tailored interventions reduces the DNT .