颅脑损伤患者D-二聚体定量测定对判断伤情、预后的研究

目的:探讨D-二聚体(DD)含量与颅脑损伤病人伤情、预后的相关性。方法:应用DD定量测定的方法,检测55例不同伤情的颅脑损伤病人血浆中DD的含量,探讨DD含量与格拉斯哥昏迷分级(GCS),格拉斯哥预后分级(GOS)及脑损伤病理类型的关系。结果:颅脑损伤组DD含量明显高于对照组;DD含量与GCS、GOS呈负相关,而与脑损伤病理类型无关。结论:血浆DD的定量测定有助于早期、准确地判断颅脑损伤伤情与预后。     

颅脑损伤后凝血障碍研究进展

1972年Druskin等[1]首次报告1例颅脑火器伤引起弥散性血管内凝血(disseminated intravascular coagulation,DIC)后,脑外伤所致凝血障碍导致的凝血病(coagulopathy)得到了学者们的普遍重视.现已明确,凝血障碍是脑外伤常见并发症,是二次脑损伤的主要原因之一,颅脑损伤激活凝血系统造成高凝状态及其随后发生的纤溶亢进可加重脑损害,影响预后.颅脑损伤严重程度与凝血障碍、迟发颅内血肿之间以及凝血障碍与不良预后之间是密切相关的.     

重型颅脑损伤急性期血浆纤维蛋白原和D-二聚体动态改变的临床意义

目的 观察重型颅脑损伤患者不同时间、不同部位血标本中血浆纤维蛋白原(Fbg)和D-二聚体(D-dimer)的变化及其与预后的关系.方法 本组共33例单纯性颅脑损伤患者,在颅脑损伤后4h、8 h、16h、24h、36h、48h分别检测患者动脉、外周静脉、颈静脉三处血标本中Fbg和D-dimer水平并进行统计学分析.结果 颅脑损伤后4 h时Fbg值高于正常水平,此后出现降低,16h降至低于正常值.24h后Fbg水平出现回升.但颈静脉血标本比外周静脉和动脉血标本回升慢,差异有统计学意义(P<0.05);D-dimer伤后4 h即出现升高,随着时间推移逐渐下降.在48 h内仍保持高于正常水平.预后不良与预后良好患者在相同时间点的Fbg和D-dimer值比较,差异有统计学意义(P<0.05).结论 颅脑损伤后急性期出现凝血功能异常,表现为Fbg含量的降低,其降解产物D-dimer含量的显著升高,反映了脑内出现高凝状态和继发性纤溶亢进.提示凝血功能的变化可作为评价患者伤情和影响患者预后的一个因素.     

凝血功能异常对急性颅脑损伤患者预后的影响

目的 探讨凝血功能异常对急性颅脑损伤患者预后的影响.方法 选取2010-01-2012-03来本院就诊的重型颅脑损伤186例为实验组,选取本院同期健康体检者70例为对照组,检测PT、Fb、D-D、Plt含量.实验组患者均于入院24 h、3 d、7 d、14 d时检测凝血指标,对照组晨起抽取空腹血检测.结果 实验组患者入院24 h内凝血功能异常发生率42.47%（79/186）,入院3 d发生率24.19%（45/186）,入院7 d发生率4.79%（8/167）,入院14 d发生率3.27%（5/153）.入院24 h内凝血功能异常发生率显著高于7、14 d,差异有统计学意义（P〈0.05）.实验组患者入院后24 h内PT、Fb、D-D、Plt与对照组比较,差异均有统计学意义（P＜0.05）;入院7、14 d,D-D显著高于对照组,差异有统计学意义（P＜0.05）.结论 对颅脑损伤患者病情及预后的评估,不能仅依靠影像学手段,同时要参考凝血功能等实验室检查.     

急性颅脑损伤凝血功能变化对病情进展及预后的影响

目的探讨急性颅脑损伤凝血功能变化对病情进展及预后影响。 方法回顾性分析广州脑科医院神经外科与海军青岛特勤疗养中心自2017年1月至2018年12月收治的急性颅脑损伤患者71例,根据GCS评分将颅脑损伤分为轻型、中型、重型、特重型。分析颅脑损伤前后凝血功能变化与颅脑损伤严重程度、治疗方式及GOS评分的关系。 结果轻型、中型、重型及特重型颅脑损伤的国际标准化比值（INR）、凝血酶原时间（PT）、凝血活酶时间（APTT）、纤维蛋白原（FIB）、D-二聚体（D-d）及血小板（PLT）比较差异有统计学意义（P<0.05）;随访2 d~24个月,4型颅脑损伤恢复良好率分别为93.75%、80%、55.55%、0%,差异有统计学意义（P<0.05）,且急性颅脑损伤预后与颅脑损伤严重程度之间存在显著正相关（r=0.666,P<0.05）。不同颅脑损伤患者不同预后的凝血因子指标比较,INR值、PT、APTT、FIB及D-d延长,差异有统计学意义（P<0.05）,而PLT减少,差异无统计学意义（P>0.05）。 结论急性颅脑损伤后存在凝血功能异常,颅脑外伤性凝血功能障碍对于患者病情的严重程度和预后判断有重要的价值,可为判断急性颅脑损伤预后提供依据。     

亚低温疗法对重型颅脑损伤患者凝血与纤溶系统的影响

目的　探讨亚低温疗法对重型颅脑损伤患者凝血与纤溶系统的影响。方法　比较亚低温治疗与未采用亚低温治疗 (常规治疗组 )颅脑损伤患者的血小板计数 (PC) ,凝血酶原时间 (PT) ,活化部分凝血活酶时间 (APTT) ,D -二聚体 (DD)变化。结果　常规治疗组PC ,PT ,DD于伤后第 3天异常最为显著 ,第 5天异常呈减轻趋势。亚低温治疗组PC ,PT及DD伤后第 3天异常呈减轻趋势 ,伤后第 5天基本恢复正常 ,两组比较有显著差异 (P <0 .0 5 ,P <0 .0 1)。APTT异常率两组比较无统计学差异。结论　亚低温疗法能有效改善颅脑损伤后高凝状态 ,是颅脑损伤后凝血与纤溶异常的有效干预措施     

创伤性凝血病对重型颅脑损伤患者预后的影响

目的探讨创伤性凝血病对重型颅脑损伤患者预后的影响。方法将我院2009-02—2012-02收治的100例重型颅脑损伤患者分为观察组和对照组,有创伤性凝血病的39例为观察组,无创伤性凝血病的61例为对照组。比较2组患者治疗4周后GCS评分、并发症发生率及病死率的不同。结果对照组与观察组的病死率分别为11.47%和30.77%,对照组并发症发生率及GCS评分均明显优于观察组,差异有统计学意义(P<0.01)。结论创伤性凝血病不利于重型颅脑损伤的预后及转归,术后应监测患者的凝血功能。     

血管内降温对重度颅脑损伤早期凝血功能的影响

目的探讨血管内降温对重度颅脑损伤患者早期凝血功能及预后的影响。方法将2015-01—2016-06收入我院ICU的重度颅脑损伤患者按随机数字表法分为治疗组(23例)和对照组(23例),治疗组患者入院后立即应用血管内降温仪行亚低温治疗,对照组采用体表降温毯行亚低温治疗,其余治疗2组相同。记录2组患者达到目标温度所用时间,并分别于入院后0、4、8、12h及24h动态测定凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)及纤维蛋白原(Fg)、D-二聚体浓度,统计2组患者迟发性血肿和脑梗死发生率,3个月后应用格拉斯哥预后评分(GOS)评估预后。结果治疗组较对照组提前达到目标温度;治疗组治疗4h时高凝状态开始改善,8h时高凝状态明显改善,12h以后凝血功能趋于稳定;对照组治疗8h时高凝状态开始改善,12h时高凝状态明显改善,24h时凝血功能趋于稳定;2组迟发性血肿的发生率无显著差异(P0.05),脑梗死的发生率有显著差异(P0.05);3个月后治疗组GOS评分为1的例数显著低于对照组,评分为4的例数显著高于对照组,2和3分差异无统计学意义(P0.05)。结论血管内降温方法较体表降温更早的达到目标温度,可更早改善重度颅脑损伤患者伤后的高凝状态,降低脑梗死并发症发生率,改善重度颅脑损伤患者的预后。     

颅脑损伤并发播散性血管内凝血

播散性血管内凝血(Disseminated Intravascular Coagulation，简称DIC)常并发于产科疾病、严重感染或创伤及肿瘤等原发病，是一种死亡率极高的并发症。在颅脑损伤的患者中，其发病机制、临床表现、诊断及治疗都有特殊性，故综述于下：     

颅脑损伤后凝血与纤溶系统的异常改变

颅脑损伤能激活凝血系统造成高凝状态 ,这种高凝状态及随后发生的纤溶亢进可加重脑损害 ,影响预后。本文就颅脑损伤后凝血与纤溶系统异常改变的研究现状、发生机制、对预后的影响、诊断和治疗进行综述。     

Evaluation of modified non-overt DIC criteria on the prediction of poor outcome in patients with sepsis

Background

The diagnostic performance of modified criteria for non-overt disseminated intravascular coagulation (DIC) with the addition of antithrombin (AT) levels, protein C (PC) levels, and organ system failure scoring (OSF) to the International Society on Thrombosis and Hemostasis (ISTH) criteria for non-overt DIC was studied to determine the effect on predicting poor outcome in patients with sepsis.

Methods

In total, 135 consecutive patients were studied. Hemostatic markers (platelet count, prothrombin time, D-dimer, AT, PC) were examined on days 0, 1, 2, 3, 4, and 7. ISTH overt and non-overt DIC scoring, OSF, and 28-day mortality were analyzed.

Results

The numbers of patients with overt DIC, non-overt DIC and non-DIC were 42, 17 and 76 respectively. The 28-day mortality rates for ISTH overt DIC, ISTH non-overt DIC, and non-DIC were 47.6, 47.1, and 9.2%, respectively. By adding AT and PC to the ISTH non-overt DIC criteria, the 28-day mortality rate of overt DIC, non-overt DIC, and non-DIC changed to 47.6, 25.0, and 6.7%, respectively. By adding OSF to the ISTH non-overt DIC criteria to predict 28-day mortality in septic patients, receiver operating characteristic (ROC) curve analysis demonstrated that the area under the curve (AUC) of ISTH non-overt DIC (0.777) was significantly increased to 0.878 (P = 0.018). However, neither AT nor PC increased the AUC.

Conclusions

Addition of OSF to the ISTH criteria for non-overt DIC gives a better prediction of poor outcome in patients with sepsis.     

Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality

Introduction

Disseminated intravascular coagulation (DIC) with an antifibrinolytic phenotype is characterized by microvascular thrombosis leading to poor outcome at the late-stage of trauma. To test the hypothesis that DIC with a fibrinolytic phenotype at an early stage of trauma also contributes to a poor outcome due to severe bleeding, we conducted a retrospective, cohort study.

Materials and Methods

The subjects included 314 consecutive severe trauma patients. A systematic review of medical records of the patients was conducted to provide the base line characteristics and DIC-related variables. The data of these variables were obtained at 4 time points within 24 hr after arrival to the emergency department (ED); Time Point 1, immediately after arrival to the ED to 4 hr after arrival; Time Point 2, 4 to 8 hr after arrival; Time Point 3, 8 to 16 hr after arrival; Time Point 4, 16 to 24 hr after arrival.

Results

Nonsurvivors (87.3%, 48/55) met the Japanese Association for Acute Medicine (JAAM) DIC criteria showing lower fibrinogen levels, a prolonged prothrombin time, and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels in comparison to those of the 289 survivors. The FDP/D-dimer ratio and lactate level were significantly higher in the nonsurvivors than those of the survivors. Lower fibrinogen levels and higher FDP/D-dimer ratio suggest fibrinogenolysis in DIC of the nonsurvivors. Furthermore a stepwise logistic regression analysis showed that the JAAM DIC score, levels of fibrinogen, FDP and lactate at Time Point 1 are independent predictors of death. Low levels of fibrinogen and high FDP but not D-dimer predict massive bleeding at an early stage of trauma. The optimal cutoff points for the prediction of death and massive bleeding were fibrinogen (1.90, 1.90 g/L) and FDP (35.2, 68.7 mg/L), respectively.

Conclusions

DIC with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma contributes to poor prognosis due to massive bleeding. Tissue hypoperfusion may be involved in the pathogenesis of this type of DIC.     

弥散性血管内凝血（DIC）评分预测颅脑损伤进展性出血和预后的作用：352例分析

Coagulation abnormalities,such as disseminated intravascular coagulation(DIC),are associated with progressive hemorrhagic injury(PHI)following head trauma.However,the exact relationship between coagulopathy and PHI remains unclear.The present study utilized a scoring system defined by the International Society of Thrombosis and Haemostasis to investigate whether a high DIC score is predictive for PHI.This study was a multicenter prospective design involving four hospitals,a 6-month observation,and follow-up.Of 352 traumatic brain injury(TBI)patients,serial CT scan indicated approximately one third of patients developed progressive hemorrhage,which was most frequently observed in the frontal,temporal,and orbitofrontal lobes of patients with brain contusion.PHI-positive patients exhibited poor prognosis,as indicated by prolonged length of hospital/intensive care unit stay and high mortality.More importantly,a DIC score after TBI,as well as patient age and sex,could serve as predictors for PHI.In addition,DIC scores were closely associated with injury severity.Therefore,the DIC scoring system facilitated early PHI diagnosis in TBI patients,and DIC scores might serve as a valuable predictor for TBI patients with PHI.     

Implementation of the ISTH classification of non-overt DIC in a thromboplastin induced rabbit model

Validation of animal models of disseminated intravascular coagulation (DIC) to human DIC is crucial in order to translate findings in research models to treatment modalities for DIC in humans. ISTH classifications of overt and non-overt human DIC have proven to have a high diagnostic accuracy, but the scoring systems have rarely been applied to animal models of DIC. In this study, we use rabbit brain thromboplastin (thromboplastin) to induce DIC in a rabbit model and test the applicability of the ISTH criteria for standardized diagnosis of DIC.Cardiovascular and haematological parameters from rabbits, either saline-injected or administered 0.625, 1.25, 2.5 or 5 mg thromboplastin/kg as a single bolus, were collected at four timepoints over a 90 minute period. All groups of rabbits were scored at each time point according to the ISTH diagnostic criteria for non-overt DIC.Injection of 5 mg thromboplastin/kg was lethal. For the remaining groups, a dose dependent decrease in blood pressure, platelet count and fibrinogen level together with a dose dependent increase in prothrombin time, activated partial thromboplastin time, level of thrombin-antithrombin complexes, fibrin degradation products and number of thrombi in lung vasculature was seen.The administration of a bolus of 1.25 - 2.5 mg thromboplastin/kg to rabbits induced a reproducible dose dependent model of non-overt DIC according to the ISTH diagnostic criteria. We conclude that the non-overt ISTH score can be applied to evaluate severity and progression of DIC in a standardized manner in this thromboplastin induced rabbit model.     

Neurobehavioral functional deficits following closed head injury in the neonatal pig

Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.     

颅脑损伤病人预后预测的临床研究

本文研究了200例颅脑损伤病人的年龄、格拉斯哥昏迷分级(GCS)、脑干反射、运动姿势及生命体征等临床指标与预后的关系,并用这些指标组成了一种新记分法,并用此方法对病人的预后进行预测。研究表明,年龄、GCS、脑干反射、运动姿势及生命体征都与预后有密切关系,用这些指标组成的新记分法预测预后,比用GCS和Glasgow—Liege分级(GLS)有更大的优越性。     

Consumption of plasma factor VII in a rabbit model of non-overt disseminated intravascular coagulation

Introduction: We have recently described an experimental animal model of non-overt disseminated intravascular coagulation (DIC) in the rabbit in which the induction of tissue factor (TF) mRNA and TF antigen expression in peripheral blood leukocytes (PBL) was demonstrated to occur within 2 h of administration of low-dose endotoxin [Hematol. J. 2 (2001) 188]. In the present study, we demonstrate that the leukocyte TF expressed has procoagulant activity leading to a rapid decline in the concentration of factor VII (FVII) in rabbit plasma. Methods: Total plasma FVII antigen and FVIIa were quantitated by rabbit FVII-specific immunoassay and FVIIa-specific clotting assays, respectively. Plasma samples from either saline-injected rabbits or rabbits administered a single bolus of 10 μg/kg Salmonella lipopolysaccharide were compared over a 24-h period. Results: Total plasma FVII antigen decreased progressively post-endotoxin injection, reaching 71% of the baseline concentration at 8 h (p<0.001, n=18), and remained low (78%) at 24 h post-injection (p<0.01, n=16), returning to normal by 48 h. Plasma FVIIa levels increased to 120% within 2 h of endotoxin injection, fell to 73% of the baseline concentration at 8 h (p<0.05, n=18) and returned to normal by 24 h post-endotoxin administration. Procoagulant activity of rabbit peripheral blood leukocytes was enhanced at 2 h (p<0.01, n=6) and 4 h (p<0.05, n=6) post-endotoxin injection. The prothrombin time (PT) was increased by <3 s, and thrombin–antithrombin (TAT) complex formation was not significantly increased in the plasma of endotoxin-treated rabbits. No significant changes in total plasma FVII antigen, FVIIa or leukocyte procoagulant activity were observed in rabbits treated with saline. Conclusions: We conclude that the activation of FVII to FVIIa and rapid consumption of total FVII/FVIIa occur very early and likely are integral events linked to the initiation and propagation of non-overt DIC induced by endotoxin.     

Beyond cell based models of coagulation: analyses of coagulation with clot "lifespan" resistance-time relationships

Cell based models of coagulation (CBM) have provided mechanistic insight into numerous hematological issues for nearly two decades. This review discusses another coagulation model system--the clot lifespan model (CLSM)--that has been designed to compliment the CBM-based approach to elucidating the mechanisms responsible for a variety of hemostatic disorders/phenomena. The CLSM is a thrombelastograph-based approach that utilizes a standardized clotting stimulus (e.g., celite, tissue factor) and a fibrinolytic stimulus (e.g., tissue type plasminogen activator) to assess clot growth and disintegration via changes in clot resistance. The CLSM utilizes parametric, elastic modulus-based parameters to document these phenomena. The CLSM has recently been employed to discern the effects of protamine and hydroxyethyl starch on key fibrinolytic-antifibrinolytic protein interactions, as well as demonstrating differences in fibrinolytic kinetics dependent on whether contact pathway proteins or tissue factor is used to initiate coagulation. The CLSM is presently being utilized to investigate the effects of ventricular assist device placement on fibrinolysis, and it is anticipated that this model system will be employed in both basic science and clinical investigations in the future.     

DIC评分在颅脑损伤中的临床应用研究

目的分析弥散性血管内凝血（DIC）评分与颅脑损伤病人病情及预后的关系,探讨其在颅脑损伤中的临床应用价值。方法采用前瞻性研究设计方法,测定并记录110例颅脑损伤病人伤后DIC评分、GCS评分及随访6个月时的GOS评分。采用SPSS15.0软件包进行统计分析。结果至随访结束,本组死亡19例。D-二聚体升高是颅脑损伤后最常见的凝血异常指标（56例,占50.9%）。DIC评分0、1、2、3、≥4分者分别为32、26、15、20、17例,病死率分别为0、0、0、20%、88.2%。GCS评分、GOS评分与DIC评分之间存在高度相关关系。结论DIC评分是评估颅脑损伤病人病情及预后的可靠指标;DIC分值越高,病人病情越重,预后越差。     

Clinical outcome after head injury in children

For at least 1 year we have done a follow-up on 178 children under the age of 18 years with head injuries treated between 1981 and 1987. The Brussel Coma Scale and the Glasgow Outcome Score were used to determine neurological deficits and patient outcome. In children with coma, there was good recovery or moderate disability in 71.4%, severe disability in 6.1%, and death in 22.5%. When all head injuries were taken into consideration, a satisfactory outcome was found in 84.3%, severe disability in 3.3%, and death in 12.4%. The outcome mainly depended on the initial coma grade, but the duration of coma or advanced age were also negative factors for outcome. In 14.8%, intracranial mass lesions showed no significant correlation with outcome. In contrast to adults, diffuse brain swelling had a satisfactory outcome in 85.1%.Presented at the 11th Meeting of the European Society for Paediatric Neurosurgery, Naples 1988