Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model
Post-TBI splenectomy may exacerbate coagulopathy and platelet activation in a murine model
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DOI：
10.1016/j.thromres.2020.08.002
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发表时间：
2020-09-01
影响因子：
7.5
通讯作者：
Goodman, Michael D.
中科院分区：
文献类型：
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作者：
Morris, Mackenzie C.;John, Devin;Goodman, Michael D.
简介：创伤性脑损伤 (TBI) 会导致急性低凝状态、亚急性高凝状态以及血栓栓塞事件风险持续升高。脾切除术与中度或重度 TBI 患者死亡率增加相关。我们假设 TBI 患者脾切除术的不良反应可能继发于病理性凝血和血小板活化变化的加剧。方法：利用已建立的小鼠体重下降 TBI 模型，并在 TBI 后立即进行脾切除术。假手术以及仅 TBI 和脾切除的小鼠被用作损伤对照。在 TBI 后 1、6 和 24 小时以及 7 天处死小鼠进行抽血。通过旋转血栓弹力测量 (ROTEM) 评估粘弹性凝血参数，并通过流式细胞术分析富含血小板的血浆样本，通过 P-选择素的表达来测量血小板活化。结果：在损伤后 6 小时，与单独 TBI 相比，TBI/脾切除术表现出低凝血性，血栓形成时间 (CFT) 延长。损伤后 24 小时，TBI/脾切除和脾切除小鼠处于高凝状态，具有较短的 CFT、较高的 α 角和增加的 MCF，尽管与单独 TBI 相比，血小板对凝块的贡献百分比较低。然而，只有 TBI/脾切除术在 7 天时继续表现出这种高凝状态。虽然 TBI/脾切除术在损伤后 1 小时具有更高的 P-选择素表达，但与 TBI/脾切除术相比，单独 TBI 在损伤后 24 小时具有显着更高的 P-选择素表达。有趣的是，P-选择素表达仅在损伤后7天的TBI/脾切除中保持升高。结论：TBI后的脾切除加剧了损伤后凝血状态的变化。 TBI 和脾切除术相结合会引起急性低凝状态，可能导致颅内出血增加。亚急性时，TBI 中添加脾切除术会加剧损伤后的高凝状态，并诱导持续的血小板活化。这些对凝血的多发性损伤可能会导致脑和脾联合损伤患者的死亡率增加。
Introduction: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes.Methods: An established murine weight-drop TBI model was utilized and a splenectomy was performed immediately following TBI. Sham as well as TBI and splenectomy alone mice were used as injury controls. Mice were sacrificed for blood draws at 1, 6, and 24 h, as well as 7 days post-TBI. Viscoelastic coagulation parameters were assessed by rotational thromboelastometry (ROTEM) and platelet activation was measured by expression of P-selectin via flow cytometry analysis of platelet rich plasma samples.Results: At 6 h following injury, TBI/splenectomy demonstrated hypocoagulability with prolonged clot formation time (CFT) compared to TBI alone. By 24 h following injury, TBI/splenectomy and splenectomy mice were hypercoagulable with a shorter CFT, a higher alpha angle, and increased MCF, despite a lower percentage of platelet contribution to clot compared to TBI alone. However, only the TBI/splenectomy continued to display this hypercoagulable state at 7 days. While TBI/splenectomy had greater P-selectin expression at 1-h post-injury, TBI alone had significantly greater P-selectin expression at 24 h post-injury compared to TBI/splenectomy. Interestingly, P-selectin expression remained elevated only in TBI/splenectomy at 7 days post-injury.Conclusion: Splenectomy following TBI exacerbates changes in the post-injury coagulation state. The combination of TBI and splenectomy induces an acute hypocoagulable state that could contribute to an increase in intracranial bleeding. Subacutely, the addition of splenectomy to TBI exacerbates post-injury hypercoagulability and induces persistent platelet activation. These polytrauma effects on coagulation may contribute to the increased mortality observed in patients with combined brain and splenic injuries.