From the W. M Keck Center for Transgene Research (F.J.C., D.L.D., V.P., P.D., M.W.), University of Notre Dame, Notre Dame; and Memorial Hospital of South Bend (S.T., R.Y., E.E., M.W.), Emergency Trauma Center; and Indiana University School of Medicine at Notre Dame Campus (B.F., P.D., M.W.), South Bend, Indiana; Department of Surgery (M.P.C., E.E.M., M.V.W.), University of Colorado; and Department of Surgery (M.P.C., E.E.M., M.V.W.), Denver Health Medical Center, Denver, Colorado; Department of Surgery (M.P.C.), Georgia Health Sciences University, Augusta, Georgia.
J Trauma Acute Care Surg. 2014 May;76(5):1169-76. doi: 10.1097/TA.0000000000000216.
Coagulopathy in traumatic brain injury (CTBI) is a well-established phenomenon, but its mechanism is poorly understood. Various studies implicate protein C activation related to the global insult of hemorrhagic shock or brain tissue factor release with resultant platelet dysfunction and depletion of coagulation factors. We hypothesized that the platelet dysfunction of CTBI is a distinct phenomenon from the coagulopathy following hemorrhagic shock.
We used thrombelastography with platelet mapping as a measure of platelet function, assessing the degree of inhibition of the adenosine diphosphate (ADP) and arachidonic acid (AA) receptor pathways. First, we studied the early effect of TBI on platelet inhibition by performing thrombelastography with platelet mapping on rats. We then conducted an analysis of admission blood samples from trauma patients with isolated head injury (n = 70). Patients in shock or on clopidogrel or aspirin were excluded.
In rats, ADP receptor inhibition at 15 minutes after injury was 77.6% ± 6.7% versus 39.0% ± 5.3% for controls (p < 0.0001). Humans with severe TBI (Glasgow Coma Scale [GCS] score ≤ 8) showed an increase in ADP receptor inhibition at 93.1% (interquartile range [IQR], 44.8-98.3%; n = 29) compared with 56.5% (IQR, 35-79.1%; n = 41) in milder TBI and 15.5% (IQR, 13.2-29.1%) in controls (p = 0.0014 and p < 0.0001, respectively). No patient had significant hypotension or acidosis. Parallel trends were noted in AA receptor inhibition.
Platelet ADP and AA receptor inhibition is a prominent early feature of CTBI in humans and rats and is linked to the severity of brain injury in patients with isolated head trauma. This phenomenon is observed in the absence of hemorrhagic shock or multisystem injury. Thus, TBI alone is shown to be sufficient to induce a profound platelet dysfunction.
创伤性脑损伤（CTBI）中的凝血功能障碍是一种已确立的现象，但其机制尚不清楚。各种研究表明，蛋白 C 的激活与出血性休克或脑组织组织因子释放引起的血小板功能障碍和凝血因子耗竭有关。我们假设 CTBI 中的血小板功能障碍是与出血性休克后凝血功能障碍不同的现象。
我们使用血栓弹力图和血小板图谱来衡量血小板功能，评估二磷酸腺苷（ADP）和花生四烯酸（AA）受体途径抑制的程度。首先，我们通过对大鼠进行血栓弹力图和血小板图谱检查，研究 TBI 对血小板抑制的早期影响。然后，我们对 70 例单纯头部损伤的创伤患者的入院血样进行了分析。排除休克或服用氯吡格雷或阿司匹林的患者。
在大鼠中，损伤后 15 分钟 ADP 受体抑制率为 77.6%±6.7%，而对照组为 39.0%±5.3%（p<0.0001）。严重 TBI（格拉斯哥昏迷评分[GCS]评分≤8）患者的 ADP 受体抑制率为 93.1%（四分位距[IQR]，44.8-98.3%；n=29），与轻度 TBI 患者的 56.5%（IQR，35-79.1%；n=41）和对照组的 15.5%（IQR，13.2-29.1%）相比明显增加（p=0.0014 和 p<0.0001）。没有患者出现明显低血压或酸中毒。AA 受体抑制也出现了类似的趋势。
在人和大鼠中，血小板 ADP 和 AA 受体抑制是 CTBI 的一个早期突出特征，与单纯头部创伤患者的脑损伤严重程度有关。这种现象发生在没有出血性休克或多系统损伤的情况下。因此，单独的 TBI 足以引起严重的血小板功能障碍。
