Recent studies of platelet inhibition and anticoagulation in SCD
| Author . | Genotypes . | Study type (N) . | Therapy . | Biomarker end point . | Clinical end point . |
|---|---|---|---|---|---|
| Desai et al26 | HbSS/Sβ thalassemia/SC | Randomized pilot13 | Eptifibatide vs placebo 2:1 | None reported | Estimated difference in major bleeding = 0.00 (95% CI, −0.604 to 0.372) |
| Wun et al27 | HbSS/Sβ thalassemia/SC | Randomized phase 2 (62) | Prasugrel vs placebo | Decrease in platelet P-selectin, soluble P-selectin, thromboxane B2, and CD40 ligand for those receiving prasugrel | 21% reduction in number of days with pain (P = .30) and 25% reduction in intensity (P = .24) |
| Styles et al28 | HbSS/Sβ0 thalassemia | Phase 2, open-label, adaptive-design, dose ranging study (33) | Prasugrel | Platelet inhibition higher at 0.12 mg/kg compared with 0.06 mg/kg or 0.08 mg/kg | Minor bleeding in 3 or 18 patients on escalating daily doses |
| Heeney et al29 | HbSS/Sβ0 thalassemia (aged 2-17) | Randomized phase 3 (341) | Prasugrel vs placebo | Decreased platelet reactivity units | VOC events 2.30 per person-year in prasugrel group and 2.77 in placebo group (rate ratio, 0.83; 95% CI, 0.66-1.05; P = .12). |
| Schnog et al30 | HbSS/SC | Randomized double-blind crossover pilot (phase 2) (22) | Acenocoumarol vs placebo | Decreased prothrombin 1.2, thrombin-antithrombin, and D-dimer on active drug | 3 VOC on acenocoumarol, 5 on placebo, not significantly different |
| Ahmed et al31 | HbSS/Sβ thalassemia/SC | Prospective observational (37) | Low-dose warfarin | Median (range) D-dimer 0.81 μg FEU/mL (0.34-1.8) on warfarin vs 3.1 μg FEU/mL (0.94-4) not receiving warfarin during VOC | None reported |
| Qari et al32 | HbSS | Randomized double-blind phase 3 (253) | Tinzaparin vs placebo | None reported | Reduction in days with worse pain (mean ± SD) (1.28 ± 0.2 vs 1.74 ± 0.15), VOC duration (2.57 ± 0.45 vs 4.35 ± 0.78), and length of stay (7.08 ± 1.8 vs 12.06 ± 2.2), all P < .05 |
| Author . | Genotypes . | Study type (N) . | Therapy . | Biomarker end point . | Clinical end point . |
|---|---|---|---|---|---|
| Desai et al26 | HbSS/Sβ thalassemia/SC | Randomized pilot13 | Eptifibatide vs placebo 2:1 | None reported | Estimated difference in major bleeding = 0.00 (95% CI, −0.604 to 0.372) |
| Wun et al27 | HbSS/Sβ thalassemia/SC | Randomized phase 2 (62) | Prasugrel vs placebo | Decrease in platelet P-selectin, soluble P-selectin, thromboxane B2, and CD40 ligand for those receiving prasugrel | 21% reduction in number of days with pain (P = .30) and 25% reduction in intensity (P = .24) |
| Styles et al28 | HbSS/Sβ0 thalassemia | Phase 2, open-label, adaptive-design, dose ranging study (33) | Prasugrel | Platelet inhibition higher at 0.12 mg/kg compared with 0.06 mg/kg or 0.08 mg/kg | Minor bleeding in 3 or 18 patients on escalating daily doses |
| Heeney et al29 | HbSS/Sβ0 thalassemia (aged 2-17) | Randomized phase 3 (341) | Prasugrel vs placebo | Decreased platelet reactivity units | VOC events 2.30 per person-year in prasugrel group and 2.77 in placebo group (rate ratio, 0.83; 95% CI, 0.66-1.05; P = .12). |
| Schnog et al30 | HbSS/SC | Randomized double-blind crossover pilot (phase 2) (22) | Acenocoumarol vs placebo | Decreased prothrombin 1.2, thrombin-antithrombin, and D-dimer on active drug | 3 VOC on acenocoumarol, 5 on placebo, not significantly different |
| Ahmed et al31 | HbSS/Sβ thalassemia/SC | Prospective observational (37) | Low-dose warfarin | Median (range) D-dimer 0.81 μg FEU/mL (0.34-1.8) on warfarin vs 3.1 μg FEU/mL (0.94-4) not receiving warfarin during VOC | None reported |
| Qari et al32 | HbSS | Randomized double-blind phase 3 (253) | Tinzaparin vs placebo | None reported | Reduction in days with worse pain (mean ± SD) (1.28 ± 0.2 vs 1.74 ± 0.15), VOC duration (2.57 ± 0.45 vs 4.35 ± 0.78), and length of stay (7.08 ± 1.8 vs 12.06 ± 2.2), all P < .05 |
Adapted from Ataga and Key.48