直接红细胞对血栓形成的影响取决于组织因子和钙与膜磷脂酰丝氨酸的相互作用。
Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.
机构信息
From the Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
出版信息
J Trauma Acute Care Surg. 2024 Jul 1;97(1):57-64. doi: 10.1097/TA.0000000000004340. Epub 2024 Apr 12.
BACKGROUND
Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor.
METHODS
Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow.
RESULTS
Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model.
CONCLUSION
Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.
背景
先前的文献表明红细胞（RBC）在血栓形成的启动中起作用，并表明输血后高凝状态可能继发于 RBC 的作用。升高的血清组织因子是急性创伤的已知后遗症。磷脂酰丝氨酸（PS）是存在于 RBC 细胞膜内的促血栓形成磷脂。我们假设 RBC 聚集依赖于 RBC 膜结合（暴露）PS、细胞外钙和组织因子之间的相互作用。
方法
将人全血（WB）分离成成分，包括 RBC 和富含血小板的血浆（PRP）。全血、PRP 和 RBC 进行了利用花生四烯酸（AA）、ADP、胶原、钙和组织因子（TF）激动剂的阻抗聚集测量。然后，RBC 进行了利用钙和 TF 激动剂的阻抗聚集测量。用已知的 PS 阻断剂 Annexin V 预处理 RBC，并进行了钙和 TF 联合激动剂的阻抗聚集测量，以确定钙/TF 诱导的 RBC 聚集性的机制是否依赖于 PS。用钙、TF、钙+TF 处理的 RBC 和用 Annexin V 预处理后用钙+TF 处理的 RBC 被灌注到体外肺微循环模型中。
结果
当使用 TF 激动剂时，RBC 的聚集明显高于 WB 和 PRP，这是 TF 特有的作用。钙和 TF 的联合作用显著增加了 RBC 的聚集，而单独使用任何一种激动剂都没有这种作用。用 Annexin V 预处理后，用 TF+钙处理后的 RBC 的聚集性显著降低。老化至 42 天的 RBC 其聚集性没有明显变化。暴露于钙和 TF 可显著减少灌注通过肺微循环模型的 RBC 的血栓形成时间。
结论
TF 和钙的联合治疗可协同诱导 RBC 聚集。磷脂酰丝氨酸似乎在 TF/钙依赖性、与年龄无关的 RBC 聚集反应中起着重要作用。在体外肺微循环灌注模型中，用 TF+钙处理的 RBC 形成血栓的速度更快。
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