或许问题不在于血小板：瑞斯托霉素揭示了创伤性脑损伤后血小板聚集受损中 von Willebrand 因子的潜在作用。
Perhaps it's not the platelet: Ristocetin uncovers the potential role of von Willebrand factor in impaired platelet aggregation following traumatic brain injury.
机构信息
From the Department of Surgery (L.Z.K, A.J.R., A.S.C., A.T.F., R.A.C.,), Zuckerberg San Francisco General Hospital and the University of California, San Francisco, San Francisco, California; Department of Medicine (C.M.H., C.S.C.), San Francisco General Hospital and the University of California, San Francisco, San Francisco, California; and Department of Surgery (M.J.C.), Denver Health Medical Center and the University of Colorado; Denver, Colorado.
出版信息
J Trauma Acute Care Surg. 2018 Nov;85(5):873-880. doi: 10.1097/TA.0000000000002025.
BACKGROUND
Injury to the blood-brain barrier exposes endothelium rich in von Willebrand factor (vWF), which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance that induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole-blood multiple-electrode platelet aggregometry. We hypothesized that patients with TBI have an altered platelet aggregation response to ristocetin stimulation compared with patients without TBI.
METHODS
Blood was collected from 233 trauma patients without thrombocytopenia. Platelet aggregation was assessed using multiple-electrode platelet aggregometry (Multiplate). Platelet aggregation response to stimulating agonists collagen, thrombin receptor-activating peptide 6, adenosine diphosphate, arachidonic acid, and ristocetin was measured. Factor activity was measured.
RESULTS
Of the 233 patients, 23% had TBI. There were no differences in platelet aggregation responses to any agonists between TBI and non-TBI patients except ristocetin. Platelet aggregation response to ristocetin stimulation was significantly lower in TBI patients (p = 0.03). Patients with TBI also had higher factor VIII activity (215% vs. 156%, p = 0.01). In multivariate analysis, there was a significant independent association of impaired platelet aggregation response to ristocetin stimulation with TBI (odds ratio, 3.05; p = 0.04).
CONCLUSIONS
Given the importance of platelets in hemostasis, understanding the mechanisms of impaired platelet aggregation following injury is critical. The impaired platelet aggregation response to ristocetin stimulation and corresponding increase in factor VIII activity in TBI patients may be secondary to a TBI-induced effect on vWF quantity (due to injury-driven consumption of vWF) or vWF function with resultant increase in circulating factor VIII activity (due to impaired carrying capacity of vWF). Given there are multiple known therapies for vWF deficits including desmopressin, purified and recombinant vWF, and estrogens, these lines of investigation are particularly compelling in patients with TBI and hemorrhage.
LEVEL OF EVIDENCE
Prognostic study, level II.
背景
血脑屏障损伤使富含血管性血友病因子 (vWF) 的内皮细胞暴露，这可能在创伤性脑损伤 (TBI) 后改变血小板聚集。瑞斯托霉素是一种抗微生物物质，可诱导 vWF 介导的血小板聚集。我们通过全血多电极血小板聚集仪测量血小板对刺激剂（包括瑞斯托霉素）的聚集反应，在受伤患者中检查了这些机制。我们假设与没有 TBI 的患者相比，TBI 患者对瑞斯托霉素刺激的血小板聚集反应发生改变。
方法
从 233 例无血小板减少症的创伤患者中采集血液。使用多电极血小板聚集仪 (Multiplate) 评估血小板聚集。测量血小板对刺激剂胶原、血栓素受体激活肽 6、二磷酸腺苷、花生四烯酸和瑞斯托霉素的聚集反应。测量因子活性。
结果
在 233 名患者中，23%患有 TBI。TBI 和非 TBI 患者对任何激动剂的血小板聚集反应均无差异，除了瑞斯托霉素。TBI 患者对瑞斯托霉素刺激的血小板聚集反应明显降低（p = 0.03）。TBI 患者的因子 VIII 活性也较高（215%比 156%，p = 0.01）。多变量分析显示，瑞斯托霉素刺激引起的血小板聚集反应受损与 TBI 有显著的独立关联（比值比，3.05；p = 0.04）。
结论
鉴于血小板在止血中的重要性，了解损伤后血小板聚集受损的机制至关重要。TBI 患者对瑞斯托霉素刺激的血小板聚集反应受损和相应的因子 VIII 活性增加可能继发于 TBI 对 vWF 数量的影响（由于 vWF 消耗导致）或 vWF 功能受损，导致循环因子 VIII 活性增加（由于 vWF 携带能力受损）。鉴于有多种已知的 vWF 缺乏症治疗方法，包括去氨加压素、纯化和重组 vWF 以及雌激素，这些研究在 TBI 和出血患者中尤其引人注目。
证据水平
预后研究，II 级。
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