Weekly SCD Practice Update

Soluble C5b-9 as a Biomarker for Hemolysis-Associated Complications in Sickle Cell Disease

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.