Emma Pappano, B.S., Maria Armila Ruiz, Zalaya Ivy, M.D., M.S., Santosh Saraf, M.D.
Key Findings
- Purpose
To evaluate soluble C5b-9 (sC5b-9), a marker of terminal complement activation, as a biomarker for hemolysis-associated complications in sickle cell disease (SCD). - Population (Model)
114 adults with SCD; genotypes compared as HbSS/HbSβ⁰-thalassemia versus other variants. High sC5b-9 defined as >795 ng/ml.
- Headline Result
- Severe genotypes: 812.7 vs 610.2 ng/ml (P = 0.047); multivariate β = 0.41 (P = 0.001).
- TRJV >3 m/sec: 913.6 vs 788.8 ng/ml (P = 0.024); adjusted OR = 13.97 (P = 0.040).
- Hydroxyurea use: 719.8 vs 847.2 ng/ml (P = 0.009); β = −0.24 (P = 0.004).
- sC5b-9 correlated with hemolysis markers including LDH (β = 0.522, P = 0.013) and hemoglobinuria, and with endothelial activation (VCAM-1).
- Why It Matters
Complement activation may contribute to vascular injury and pulmonary hypertension risk in SCD, including TRJV >3 m/sec — a known predictor of early mortality. - Evidence Gaps & Limitations
Cross-sectional design limits causality; prognostic value requires longitudinal validation.
Source: Journal of Sickle Cell Disease- “Soluble C5b-9 as a Biomarker for Hemolysis-Associated Complications in Sickle Cell Disease.”
Regulatory & Guideline Watch
Current SCD guidance recommends cardiopulmonary screening but lacks validated laboratory biomarkers for risk stratification.