Shear Rate Dependency of Red Cell Sequestration in Skin Capillaries in Sickle Cell Disease and Its Variation with Vasoocclusive Crisis

Abstract

Objective: To develop techniques for assessing the sequestration of red blood cells (RBCs) in skin capillaries of sickle cell disease (SCD) patients due to RBC adhesion to endothelium (EC) and RBC aggregation, and to determine the extent to which these processes correlate with onset of painful vasoocclusive crisis.

Methods: Video recordings of nailfold capillaries in the skin of patients with SCD were made during steady-state periods and episodes of painful crisis. A transient low-flow state was induced with a pressure cuff, and reductions in RBC velocity were measured by spatial cross-correlation of light intensity along arterial and venous capillary limbs. An RBC accumulation index (AI) was calculated from RBC flow to represent the percentage of arterial in-flow sequestered in a capillary. An index of hematocrit (HI) was derived from axial distributions of light intensity, and a sequestration index (SI) was calculated to represent the relative increase of venous limb HI relative to that in the arterial limb with onset of stasis.

Results: Both AI and SI increased dramatically from zero at steady flow to a maximum as shear rates within the capillary were reduced to zero. The increase was small until shear rates (γ) fell below a transition value (γ_T), following which both AI and SI increased sharply with onset of stasis. For 20 ≤ γ < γ_T the transient increase in AI was significantly elevated in the order AI_CRISIS > AI_{STEADY STATE} > AI_CONTROL, thus reflecting increasing RBC sequestration in the venous limb due to either adhesion or aggregation. Compaction of RBCs in the venous limb was evidenced by increased SI that was greater than control for both steady-state and crisis subjects, but insignificantly elevated during crisis compared to steady state, thus supporting a lesser role of RBC aggregation.

Conclusions: Transient sequestration of sickle RBCs in the low-flow state appears to be dominated by RBC-EC adhesion, which becomes enhanced during crisis. Although aggregation may enhance adhesive contact of RBCs with EC, it does not increase to the same extent as the rate of sequestration, thus reflecting a greater role of RBC-EC adhesion.

Key Words:

• sickle cell disease
• nailfold microscopy
• erythrocyte-endothelium adhesion
• vasocclusive crisis
• red cell aggregation