Aafke E. Gaartman

Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolytic anemia and recurrent microvascular occlusions, resulting in acute painful events and progressive organ damage. Although primarily a red blood cell disorder, the pathophysiology of SCD is increasingly characterized as a complex interplay between several different cell types and cellular processes. Evidence is accumulating that neutrophils are phenotypically different in SCD and have a significant contribution in the pathophysiology of the disease. In this review, we summarize the currently available evidence on the role of neutrophils in SCD pathophysiology, demonstrating that neutrophils in SCD have an activated phenotype and play an important role in vaso‐occlusion and inflammation in SCD. Activation of neutrophils in SCD is primarily driven by hemolysis and ischemia–reperfusion injury. The ameliorating effects of treatments, for example, hydroxyurea, might be partly mediated by decreasing neutrophil counts and reversing the pro‐inflammatory properties. Whether the novel anti‐sickling therapies, reducing hemolysis, have an anti‐inflammatory effect on neutrophils, remains to be elucidated.

Summary: Intravenous fluid therapy (IV‐FT) is routinely used in the treatment of vaso‐occlusive crises (VOCs), as dehydration possibly promotes and sustains erythrocyte sickling. Patients with sickle cell disease (SCD) are at risk of developing diastolic dysfunction and fluid overload due to IV‐FT. However, data on the adverse effects of IV‐FT for VOC is sparse. We aimed to evaluate the incidence and risk factors of fluid overload due to IV‐FT in patients with SCD. Consecutive hospitalisations for VOC treated with IV‐FT between September 2016 and September 2018 were retrospectively analysed. The median (interquartile range) age was 25·0 (18·3–33·8) years and 65% had a severe genotype (HbSS/HbSβ⁰‐thal). Fluid overload occurred in 21% of 100 patients. Hospital stay was longer in patients with fluid overload (6·0 vs. 4·0 days, P = 0·037). A positive history of fluid overload (P = 0·017), lactate dehydrogenase level (P = 0·011), and top‐up transfusion during admission (P = 0·005) were independently associated with fluid overload occurrence. IV‐FT was not reduced in 86% of patients despite a previous history of fluid overload. Fluid overload is frequently encountered during IV‐FT for VOC. IV‐FT is often not adjusted despite a positive history of fluid overload or when top‐up transfusion is indicated, emphasising the need for more awareness of this complication and a personalised approach.