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Platelets compensate for poor thrombin generation in type 3 von Willebrand disease.

血小板代偿 3 型血管性血友病凝血酶生成不良。

  • 影响因子:2.36
  • DOI:10.1080/09537104.2019.1581922
  • 作者列表:"Szanto T","Nummi V","Jouppila A","Brinkman HJM","Lassila R
  • 发表时间:2020-01-01
Abstract

:In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to in vitro thrombin generation (TG) and platelet procoagulant activity in VWD3. TG was assessed by calibrated automated thrombogram (CAT) in platelet-poor (PPP) and -rich plasma (PRP) from 9 patients before and in 6 patients also 30 min after receiving their regular VWF therapy. Responsiveness of PPP to FVIII and protein S was also investigated. TG data were compared with routine laboratory variables, rotational thromboelastometry (ROTEM) and platelet expression of P-selectin and phosphatidylserine in flow cytometry. Compared with healthy controls, TG was markedly decreased in VWD3 PPP (peak thrombin was 16% of normal median), but not in PRP (77% of normal median) (p = 0.002). Six out of nine patients (67%) were high responders in their platelet P-selectin, and 5/9 (56%) in phosphatidylserine expression. Replacement therapy improved TG in PPP, while in PRP TG only modestly increased or was unaffected. In PPP, FVIII levels associated with TG and in vitro FVIII-supplemented TG inclined up to threefold. Conversely, a FVIII inhibitory antibody reduced plasma TG in all, but especially in patients with remnant FVIII levels. Inhibition of protein S improved plasma TG, particularly at low FVIII levels. ROTEM failed to detect VWD3.In VWD3, TG is reduced in PPP and regulated by FVIII and protein S, but TG is close to normal in PRP. VWD3 platelets seem to compensate for the FVIII-associated reduction in TG by their exposure of P-selectin and phosphatidylserine.

摘要

: 在 3 型血管性血友病 (VWD 3) 中,血管性血友病因子 (VWF) 缺失的最严重形式,出血表型是可变的。血小板对VWD3 止血缺陷的贡献需要进一步研究。我们在vwd3 中研究了血小板对体外凝血酶生成 (TG) 和血小板促凝血活性的贡献。通过校准的自动血小板图 (CAT) 评估血小板缺乏 (PPP) 和富血浆 (PRP) 中的TG 9 例患者在接受常规VWF治疗前,6 例患者在接受常规VWF治疗后 30 min。Re s pon s ivene s s of PPP to FVIII and protein S wa s al s o inve s tigated.TG数据与常规实验室变量、旋转血栓弹力图 (ROTEM) 和流式细胞术中血小板P-选择素和磷脂酰丝氨酸的表达进行比较。与健康对照组相比,VWD3 PPP的TG显著降低 (凝血酶峰值为正常中位数的 16%),而PRP (正常中位数的 77%) 则不显著降低 (p = 0.002)。9 例患者中有 6 例 (67%) 在血小板P-选择素和磷脂酰丝氨酸表达方面为高应答者,分别为 5/9 (56%)。替代治疗改善了PPP的TG,而PRP的TG仅适度增加或不受影响。在PPP中,与TG相关的FVIII水平和体外补充FVIII的TG倾向于 3 倍。相反,FVIII抑制性抗体可降低血浆TG,尤其是残留FVIII水平的患者。抑制蛋白S改善pla s ma TG,特别是在低FVIII水平s。ROTEM未能检测到VWD3。在VWD3 中,TG i s在PPP中降低,并受FVIII和蛋白S的调节,但TG i s clo s e在PRP中降至正常。VWD3 血小板似乎通过暴露于P-选择素和磷脂酰丝氨酸来补偿FVIII相关的TG降低。

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翻译标题与摘要 下载文献
影响因子:2.36
发表时间:2020-01-01
来源期刊:Platelets
DOI:10.1080/09537104.2019.1581922
作者列表:["Szanto T","Nummi V","Jouppila A","Brinkman HJM","Lassila R"]

METHODS::In type 3 von Willebrand disease (VWD3), the most severe form with absent von Willebrand factor (VWF), the bleeding phenotype is variable. Platelet contribution to the hemostatic defect in VWD3 calls upon further studies. We investigated the contribution of platelets to in vitro thrombin generation (TG) and platelet procoagulant activity in VWD3. TG was assessed by calibrated automated thrombogram (CAT) in platelet-poor (PPP) and -rich plasma (PRP) from 9 patients before and in 6 patients also 30 min after receiving their regular VWF therapy. Responsiveness of PPP to FVIII and protein S was also investigated. TG data were compared with routine laboratory variables, rotational thromboelastometry (ROTEM) and platelet expression of P-selectin and phosphatidylserine in flow cytometry. Compared with healthy controls, TG was markedly decreased in VWD3 PPP (peak thrombin was 16% of normal median), but not in PRP (77% of normal median) (p = 0.002). Six out of nine patients (67%) were high responders in their platelet P-selectin, and 5/9 (56%) in phosphatidylserine expression. Replacement therapy improved TG in PPP, while in PRP TG only modestly increased or was unaffected. In PPP, FVIII levels associated with TG and in vitro FVIII-supplemented TG inclined up to threefold. Conversely, a FVIII inhibitory antibody reduced plasma TG in all, but especially in patients with remnant FVIII levels. Inhibition of protein S improved plasma TG, particularly at low FVIII levels. ROTEM failed to detect VWD3.In VWD3, TG is reduced in PPP and regulated by FVIII and protein S, but TG is close to normal in PRP. VWD3 platelets seem to compensate for the FVIII-associated reduction in TG by their exposure of P-selectin and phosphatidylserine.

影响因子:1.41
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DOI:10.1177/1078155219843987
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主要包括小儿贫血、血友病、急性白血病及特发性血小板减少性紫癫等疾病。

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