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Sickle cell disease (SCD) is a widely spread inherited hemoglobinopathy that includes a group of congenital hemolytic anemias, all characterized by the predominance of sickle hemoglobin (HbS). Its features are anemia, predisposal to bacterial infections and complications such as vaso-occlusive crisis (VOC) or delayed hemolytic transfusion reaction (DHTR), which lead to increased rate of morbidity and mortality even in the era of hydroxyurea. The interaction between sickle cells, neutrophils, platelets or endothelial cells in small vessels results in hemolysis and has been considered the disease's main pathophysiological mechanism. Complement activation has been reported in small cohorts of SCD patients, but the governing mechanism has not been fully elucidated. This will be important to predict the patient group that would benefit from complement inhibition. Until now, eculizumab-mediated complement inhibition has shown beneficial effects in DHTR, with limited reports in patients with VOC. In the meantime, several innovative agents are under clinical development Our state-of-the-art review summarizes current data on 1) complement activation in SCD both in steady state and crisis, 2) underlying mechanisms of complement over-activation for the clinician in the context of SCD, 3) actions of hydroxyurea and new therapeutic approaches including indirect involvement in complement activation, and 4) novel paradigms in complement inhibition.

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Aims: Achieving the low-density lipoprotein cholesterol (LDL-C) goal following an acute coronary syndrome (ACS) is a milestone often missed due to suboptimal adherence to secondary prevention treatments. Whether improved adherence could result in reduced LDL-C levels is unclear. We aimed to evaluate an educational-motivational intervention to increase long-term lipid-lowering therapy (LLT) adherence and LDL-C goal attainment rate among post-ACS patients. Methods: IDEAL-LDL was a parallel, two-arm, single-center, pragmatic, investigator-initiated randomized controlled trial. Hospitalized patients for ACS were randomized to a physician-led integrated intervention consisting of an educational session at baseline, followed by regular motivational interviewing phone sessions or usual care. Co-primary outcomes were the LLT adherence (measured by Proportion of Days Covered (PDC); good adherence de ned as PDC>80%), and LDL-C goal (<70 mg/dl or 50% reduction from baseline) achievement rate at one year. Results: In total, 360 patients (mean age 62 years, 81% male) were randomized. Overall, good adherence was positively associated with LDL-C goal achievement rate at one year. Median PDC was higher in the intervention group than the control group [0.92 (IQR, 0.82-1.00) vs. 0.86 (0.62-0.98); p=0.03] while the intervention group had increased odds of good adherence (adjusted odds ratio: 1.76 (95% con dence interval 1.02 to 2.62; p=0.04). However, neither the rate of LDL-C goal achievement (49.6% in the intervention vs. 44.9% in the control group; p=0.49) nor clinical outcomes differed signi cantly between the two groups. Conclusion: Α multifaceted intervention improved LLT adherence in post-ACS patients without a signi cant difference in LDL-C goal attainment.