First Author | Chen 陈温纯 W | Year | 2019 |
Journal | Arterioscler Thromb Vasc Biol | Volume | 39 |
Issue | 10 | Pages | 2028-2037 |
PubMed ID | 31315441 | Mgi Jnum | J:339795 |
Mgi Id | MGI:6709644 | Doi | 10.1161/ATVBAHA.119.312439 |
Citation | Chen W, et al. (2019) Short-Acting Anti-VWF (von Willebrand Factor) Aptamer Improves the Recovery, Survival, and Hemostatic Functions of Refrigerated Platelets. Arterioscler Thromb Vasc Biol 39(10):2028-2037 |
abstractText | OBJECTIVE: Refrigeration-induced binding of VWF (von Willebrand factor) to platelets contributes to the rapid clearance of refrigerated platelets. In this study, we investigate whether inhibiting VWF binding by a DNA-based aptamer ameliorates the clearance of refrigerated platelets without significantly impeding hemostatic functions. Approach and Results: Platelets were refrigerated with or without aptamer ARC1779 for 48 hours. VWF binding, the effective lifetime of ARC1779, platelet post-transfusion recovery and survival, and the hemostatic function were measured. ARC1779 treatment during refrigeration inhibited the platelet-VWF interaction. ARC1779-treated refrigerated murine platelets exhibited increased post-transfusion recovery and survival than untreated ones (recovery of ARC1779-treated platelets: 76.7+/-5.5%; untreated: 63.7+/-0.8%; P<0.01. Half-life: 31.4+/-2.36 hours versus 28.1+/-0.86 hours; P<0.05). A similar increase was observed for refrigerated human platelets (recovery: 49.4+/-4.4% versus 36.8+/-2.1%, P<0.01; half-life: 9.2+/-1.5 hours versus 8.7+/-0.9 hours, ns). The effective lifetime of ARC1779 in mice was 2 hours. Additionally, ARC1779 improved the long-term (2 hours after transfusion) hemostatic function of refrigerated platelets (tail bleeding time of mice transfused with ARC1779-treated refrigerated platelets: 160+/-65 seconds; untreated: 373+/-96 seconds; P<0.01). The addition of an ARC1779 antidote before transfusion improved the immediate (15 minutes after transfusion) hemostatic function (bleeding time of treated platelets: 149+/-21 seconds; untreated: 320+/-36 seconds; P<0.01). CONCLUSIONS: ARC1779 improves the post-transfusion recovery of refrigerated platelets and preserves the long-term hemostatic function of refrigerated platelets. These results suggest that a short-acting inhibitor of the platelet-VWF interaction may be a potential therapeutic option to improve refrigeration of platelets for transfusion treatment. |