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Publication : Short-Acting Anti-VWF (von Willebrand Factor) Aptamer Improves the Recovery, Survival, and Hemostatic Functions of Refrigerated Platelets.

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.
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