A comparison of baseline, non-VOC values by SCD (HbSS, HbS-β0), SC trait (HbAS), and non-SCD (HbA) status
| Biomarker . | SCD geometric mean (95% CI) . | SC trait geometric mean (95% CI) . | Non-SCD geometric mean (95% CI) . | P . | |||
|---|---|---|---|---|---|---|---|
| Overall . | SC trait vs non-SCD . | SCD vs non-SCD . | SCD vs SC trait . | ||||
| Functional cellular adhesion | |||||||
| Monocyte-platelet aggregates, % | 32.56 (27.62, 38.38) | 23.33 (16.78, 32.44) | 19.65 (11.67, 33.09) | .060 | |||
| Monocyte-platelet aggregates, MFI | 128.47 (114.91, 143.64) | 87.49 (69.16, 110.67) | 79.34 (54.71, 115.06) | .002 | .659 | .016 | .004 |
| Neutrophil-platelet aggregates, % | 12.35 (10.38, 14.68) | 10.37 (7.32, 14.69) | 9.00 (5.19, 15.61) | .418 | |||
| Neutrophil-platelet aggregates, MFI | 63.78 (58.59, 69.42) | 44.40 (37.10, 53.14) | 38.04 (28.64, 50.53) | <.001 | .362 | .001 | .001 |
| Whole blood adhesion to VCAM-1, adherent cells/mm2 | 287.68 (236.84, 349.44) | 57.01 (39.12, 83.09) | 65.35 (36.06, 118.41) | <.001 | .699 | <.001 | <.001 |
| White blood cell adhesion to VCAM-1, adherent cells/mm2 | 404.17 (377.14, 433.14) | 438.65 (376.09, 511.62) | 510.24 (400.05, 650.78) | .145 | |||
| Whole blood adhesion to P-selectin, adherent cells/mm2 | 28.61 (24.35, 33.62) | 13.37 (9.54, 18.72) | 21.79 (12.83, 37.01) | .001 | .125 | .329 | <.001 |
| White blood cell adhesion to P-selectin, adherent cells/mm2 | 110.51 (95.09, 128.42) | 88.44 (64.16, 121.89) | 99.20 (59.73, 164.76) | .443 | |||
| Soluble E-selectin, ng/mL | 20.07 (17.10, 23.56) | 9.29 (6.88, 12.56) | 5.79 (3.59, 9.31) | <.001 | .097 | <.001 | <.001 |
| Soluble P-selectin, ng/mL | 110.05 (99.64, 121.56) | 81.02 (67.04, 97.92) | 74.76 (55.43, 100.83) | .004 | .650 | .017 | .006 |
| Soluble VCAM-1, ng/mL | 947.2 (826.9, 1084.9) | 461.4 (357.1, 596.1) | 551.0 (367.6, 826.0) | <.001 | .460 | .014 | <.001 |
| Clinical chemistries | |||||||
| Hemoglobin, g/dL | 8.27 (7.83, 8.74) | 12.19 (11.00, 13.51) | 13.75 (11.69, 16.18) | <.001 | .215 | <.001 | <.001 |
| Hemoglobin F, % | 8.16 (5.81, 11.47) | 0.10 (0.05, 0.19) | 0.23 (0.08, 0.62) | <.001 | .168 | <.001 | <.001 |
| Bilirubin, total, mg/dL | 2.44 (2.01, 2.96) | 0.31 (0.21, 0.44) | 0.34 (0.19, 0.60) | <.001 | .788 | <.001 | <.001 |
| LDH, U/L | 528.95 (473.89, 590.40) | 206.11 (167.38, 253.80) | 202.69 (145.83, 281.71) | <.001 | .932 | <.001 | <.001 |
| Cellular blood counts | |||||||
| Platelets, k/cu mm | 337.53 (305.72, 372.65) | 290.79 (240.36, 351.79) | 213.77 (158.15, 288.94) | .014 | .089 | .006 | .169 |
| Eosinophil, % | 2.52 (1.81, 3.52) | 1.46 (0.77, 2.78) | 3.72 (1.34, 10.35) | .213 | |||
| Lymphocyte, % | 33.33 (30.58, 36.33) | 35.06 (29.71, 41.38) | 45.69 (35.16, 59.38) | .080 | |||
| Absolute monocyte count, k/cu mm | 1.00 (0.87, 1.14) | 0.40 (0.31, 0.52) | 0.35 (0.23, 0.52) | <.001 | .529 | <.001 | <.001 |
| Monocyte, % | 10.11 (9.14, 11.19) | 5.94 (4.90, 7.20) | 6.33 (4.66, 8.58) | <.001 | .725 | .005 | <.001 |
| Absolute neutrophil count, k/cu mm | 4.73 (4.23, 5.29) | 3.57 (2.88, 4.44) | 2.28 (1.62, 3.22) | <.001 | .031 | <.001 | .025 |
| Neutrophil, % | 47.83 (44.69, 51.18) | 54.32 (47.69, 61.86) | 40.87 (33.27, 50.22) | .059 | |||
| Nucleated red blood cells, k/cu mm | 0.09 (0.05, 0.16) | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.01) | <.001 | .928 | <.001 | <.001 |
| Soluble inflammatory/cytokines/ markers | |||||||
| CRP, mg/L | 3.87 (2.97, 5.05) | 4.63 (2.77, 7.72) | 1.45 (0.64, 3.26) | .053 | |||
| IL-10, pg/mL | 1.72 (1.56, 1.89) | 0.70 (0.58, 0.85) | 0.65 (0.48, 0.88) | <.001 | .684 | <.001 | <.001 |
| TN-α, pg/mL | 1.78 (1.60, 1.99) | 0.93 (0.75, 1.16) | 0.93 (0.66, 1.31) | <.001 | .992 | .001 | <.001 |
| IL-6, pg/mL | 3.39 (2.24, 5.13) | 2.20 (1.00, 4.80) | 0.92 (0.27, 3.18) | .116 | |||
| Coagulation markers | |||||||
| D-dimer, µg/L | 1.26 (0.98, 1.61) | 0.42 (0.26, 0.66) | 0.25 0.12, 0.53) | <.001 | .259 | <.001 | <.001 |
| Prothrombin fragment 1+2, pmol/L | 300.53 (256.56, 352.03) | 193.51 (142.81, 262.22) | 112.31 (69.51, 181.45) | <.001 | .060 | <.001 | .013 |
| TAT complex, µg/L | 7.11 (6.20, 8.16) | 3.11 (2.35, 4.11) | 2.40 (1.55, 3.73) | <.001 | .329 | <.001 | <.001 |
| Tissue factor, pg/mL | 29.42 (26.15, 33.10) | 36.28 (29.08, 45.27) | 22.03 (15.53, 31.25) | .053 | |||
| Biomarker . | SCD geometric mean (95% CI) . | SC trait geometric mean (95% CI) . | Non-SCD geometric mean (95% CI) . | P . | |||
|---|---|---|---|---|---|---|---|
| Overall . | SC trait vs non-SCD . | SCD vs non-SCD . | SCD vs SC trait . | ||||
| Functional cellular adhesion | |||||||
| Monocyte-platelet aggregates, % | 32.56 (27.62, 38.38) | 23.33 (16.78, 32.44) | 19.65 (11.67, 33.09) | .060 | |||
| Monocyte-platelet aggregates, MFI | 128.47 (114.91, 143.64) | 87.49 (69.16, 110.67) | 79.34 (54.71, 115.06) | .002 | .659 | .016 | .004 |
| Neutrophil-platelet aggregates, % | 12.35 (10.38, 14.68) | 10.37 (7.32, 14.69) | 9.00 (5.19, 15.61) | .418 | |||
| Neutrophil-platelet aggregates, MFI | 63.78 (58.59, 69.42) | 44.40 (37.10, 53.14) | 38.04 (28.64, 50.53) | <.001 | .362 | .001 | .001 |
| Whole blood adhesion to VCAM-1, adherent cells/mm2 | 287.68 (236.84, 349.44) | 57.01 (39.12, 83.09) | 65.35 (36.06, 118.41) | <.001 | .699 | <.001 | <.001 |
| White blood cell adhesion to VCAM-1, adherent cells/mm2 | 404.17 (377.14, 433.14) | 438.65 (376.09, 511.62) | 510.24 (400.05, 650.78) | .145 | |||
| Whole blood adhesion to P-selectin, adherent cells/mm2 | 28.61 (24.35, 33.62) | 13.37 (9.54, 18.72) | 21.79 (12.83, 37.01) | .001 | .125 | .329 | <.001 |
| White blood cell adhesion to P-selectin, adherent cells/mm2 | 110.51 (95.09, 128.42) | 88.44 (64.16, 121.89) | 99.20 (59.73, 164.76) | .443 | |||
| Soluble E-selectin, ng/mL | 20.07 (17.10, 23.56) | 9.29 (6.88, 12.56) | 5.79 (3.59, 9.31) | <.001 | .097 | <.001 | <.001 |
| Soluble P-selectin, ng/mL | 110.05 (99.64, 121.56) | 81.02 (67.04, 97.92) | 74.76 (55.43, 100.83) | .004 | .650 | .017 | .006 |
| Soluble VCAM-1, ng/mL | 947.2 (826.9, 1084.9) | 461.4 (357.1, 596.1) | 551.0 (367.6, 826.0) | <.001 | .460 | .014 | <.001 |
| Clinical chemistries | |||||||
| Hemoglobin, g/dL | 8.27 (7.83, 8.74) | 12.19 (11.00, 13.51) | 13.75 (11.69, 16.18) | <.001 | .215 | <.001 | <.001 |
| Hemoglobin F, % | 8.16 (5.81, 11.47) | 0.10 (0.05, 0.19) | 0.23 (0.08, 0.62) | <.001 | .168 | <.001 | <.001 |
| Bilirubin, total, mg/dL | 2.44 (2.01, 2.96) | 0.31 (0.21, 0.44) | 0.34 (0.19, 0.60) | <.001 | .788 | <.001 | <.001 |
| LDH, U/L | 528.95 (473.89, 590.40) | 206.11 (167.38, 253.80) | 202.69 (145.83, 281.71) | <.001 | .932 | <.001 | <.001 |
| Cellular blood counts | |||||||
| Platelets, k/cu mm | 337.53 (305.72, 372.65) | 290.79 (240.36, 351.79) | 213.77 (158.15, 288.94) | .014 | .089 | .006 | .169 |
| Eosinophil, % | 2.52 (1.81, 3.52) | 1.46 (0.77, 2.78) | 3.72 (1.34, 10.35) | .213 | |||
| Lymphocyte, % | 33.33 (30.58, 36.33) | 35.06 (29.71, 41.38) | 45.69 (35.16, 59.38) | .080 | |||
| Absolute monocyte count, k/cu mm | 1.00 (0.87, 1.14) | 0.40 (0.31, 0.52) | 0.35 (0.23, 0.52) | <.001 | .529 | <.001 | <.001 |
| Monocyte, % | 10.11 (9.14, 11.19) | 5.94 (4.90, 7.20) | 6.33 (4.66, 8.58) | <.001 | .725 | .005 | <.001 |
| Absolute neutrophil count, k/cu mm | 4.73 (4.23, 5.29) | 3.57 (2.88, 4.44) | 2.28 (1.62, 3.22) | <.001 | .031 | <.001 | .025 |
| Neutrophil, % | 47.83 (44.69, 51.18) | 54.32 (47.69, 61.86) | 40.87 (33.27, 50.22) | .059 | |||
| Nucleated red blood cells, k/cu mm | 0.09 (0.05, 0.16) | 0.00 (0.00, 0.00) | 0.00 (0.00, 0.01) | <.001 | .928 | <.001 | <.001 |
| Soluble inflammatory/cytokines/ markers | |||||||
| CRP, mg/L | 3.87 (2.97, 5.05) | 4.63 (2.77, 7.72) | 1.45 (0.64, 3.26) | .053 | |||
| IL-10, pg/mL | 1.72 (1.56, 1.89) | 0.70 (0.58, 0.85) | 0.65 (0.48, 0.88) | <.001 | .684 | <.001 | <.001 |
| TN-α, pg/mL | 1.78 (1.60, 1.99) | 0.93 (0.75, 1.16) | 0.93 (0.66, 1.31) | <.001 | .992 | .001 | <.001 |
| IL-6, pg/mL | 3.39 (2.24, 5.13) | 2.20 (1.00, 4.80) | 0.92 (0.27, 3.18) | .116 | |||
| Coagulation markers | |||||||
| D-dimer, µg/L | 1.26 (0.98, 1.61) | 0.42 (0.26, 0.66) | 0.25 0.12, 0.53) | <.001 | .259 | <.001 | <.001 |
| Prothrombin fragment 1+2, pmol/L | 300.53 (256.56, 352.03) | 193.51 (142.81, 262.22) | 112.31 (69.51, 181.45) | <.001 | .060 | <.001 | .013 |
| TAT complex, µg/L | 7.11 (6.20, 8.16) | 3.11 (2.35, 4.11) | 2.40 (1.55, 3.73) | <.001 | .329 | <.001 | <.001 |
| Tissue factor, pg/mL | 29.42 (26.15, 33.10) | 36.28 (29.08, 45.27) | 22.03 (15.53, 31.25) | .053 | |||
HbS-β0, hemoglobin sickle-β; HbSS, sickle cell hemoglobin; MFI, mean fluorescence intensity.