危重病患者并发弥散性血管内凝血的早期识别

总结危重病患者并发弥散性血管内凝血（DIC）的早期识别方法和体会。护士早期识别DIC,注意易诱发DIC的基础疾病如严重感染、手术及创伤、产科疾病、恶性肿瘤及急性重症胰腺炎等。识别DIC早期临床线索：抽出的血很短时间内凝结;静脉通路易阻塞;观察患者的面色、四肢温度、肢端等部位发绀情况;皮肤淤斑,注射部位、切口、其他部位出血等。同时护士应熟知DIC相关实验室检查的异常值,如血小板计数、凝血酶原时间、活化部分凝血活酶时间、D-二聚体、纤维蛋白原等,以提高对危重病患者的抢救成功率。     

严重创伤患者血浆凝血酶原片段1+2和GMP-140水平与弥散性血管内凝血的关系

目的探讨严重创伤患者血浆凝血酶原片段1+2(F1+2)和血小板α颗粒膜蛋白-140(GMP-140)水平与弥散性血管内凝血(DIC)的关系。方法将76例创伤患者分成轻伤组(ISS评分小于16分,27例)和重伤组(ISS评分大于或等于16分,49例),再把重伤组分为并发DIC组(19例)与未并发DIC组(30例),另30例健康者为健康对照组。对76例创伤患者分别于伤后24h、3d、7d空腹采集外周静脉血,应用酶联免疫吸附(ELISA)法测定血浆凝血酶原片段1+2浓度、用放免法测定GMP-140。结果 24h内轻伤组与重伤组F1+2、GMP-140水平明显高于健康对照组,且重伤组又明显高于轻伤组。非DIC组伤后F1+2、GMP-140水平逐渐降低,DIC组伤后F1+2水平持续升高,24h内GMP-140水平明显高于非DIC组。结论创伤后急性期F1+2、GMP-140升高程度不仅与创伤严重程度有关,而且与创伤后DIC的发生密切相关;急性期外持续测定F1+2水平对预测创伤后DIC的发生具有较高的临床价值。     

Coagulopathy in COVID‐19

The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.     

Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial

BACKGROUND: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. OBJECTIVES: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. METHODS: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. RESULTS: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). CONCLUSIONS: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.     

弥散性血管内凝血快速实验室诊断指标的价值

目的 对弥散性血管内凝血（DIC）实验室快速诊断指标的敏感性、特异性及其改变的意义进行比较评估，提供理想的检测方案。方法 采用了一般实验室可行的DIC实验室诊断指标如抗凝血酶活性（AT：A，发色底物法）检测、凝血酶原时间（PT）、纤维蛋白原定量（Fbg）、D二聚体（D—D）、鱼精蛋白副凝固试验（3P）、凝血酶凝固时间（TT）等试验。结果 健康正常人77例，临床病例166例，在DIC组AT：A敏感率是91．9％，PT是89．2％，Fbg是86．5％，D—D是82．4％，3P是79．7％，TT是66．2％。结论 目前国内采用的DIC实验室诊断指标快捷实用，并具有一定的特异性和敏感性，但就诊断DIC而言多数存在较高的假阳性与假阴性。     

Disseminated intravascular coagulation in cardiac arrest and resuscitation

The aims of this review are to demonstrate that the changes in coagulation and fibrinolysis observed in cardiac arrest and resuscitation can be recognized as disseminated intravascular coagulation (DIC), and to discuss the probability of DIC being a therapeutic target. The appearance of triggers of DIC, such as damage‐associated molecular patterns, inflammatory cytokines, and adrenaline, is associated with platelet activation, marked thrombin generation and fibrin formation, insufficient anticoagulation pathways, and increased fibrinolysis by tissue‐type plasminogen activator, followed by the suppression of fibrinolysis by plasminogen activator inhibitor‐1, in patients with cardiac arrest and resuscitation. Simultaneous neutrophil activation and endothelial injury associated with glycocalyx perturbation have been observed in these patients. The degree of these changes is more severe in patients with prolonged precardiac arrest hypoxia and long no‐flow and low‐flow times, patients without return of spontaneous circulation, and non‐survivors. Animal and clinical studies have confirmed decreased cerebral blood flow and microvascular fibrin thrombosis in vital organs, including the brain. The clinical diagnosis of DIC in patients with cardiac arrest and resuscitation is associated with multiple organ dysfunction, as assessed with the sequential organ failure assessment score, and increased mortality. This review confirms that the coagulofibrinolytic changes in cardiac arrest and resuscitation meet the definition of DIC proposed by the ISTH, and that DIC is associated with organ dysfunction and poor patient outcomes. This evidence implies that established DIC should be considered to be one of the main therapeutic targets in post–cardiac arrest syndrome.     

Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a serious condition associated with sepsis. Clinical management of DIC is hampered by lack of clear diagnostic criteria. The International Society on Thrombosis and Haemostasis (ISTH) has proposed a diagnostic scoring algorithm for overt DIC based on routine laboratory tests. The objective was to assess a modified version of the ISTH scoring system and determine the effect of drotrecogin alfa (activated) (DrotAA, recombinant human activated protein C) on patients with DIC. The large database from the PROWESS clinical trial in severe sepsis was retrospectively used to assess a modified ISTH scoring system. Baseline characteristics and treatment effects of DrotAA were evaluated. At baseline, 29% (454/1568) of patients had overt DIC. Overt DIC was a strong predictor of mortality, independent of APACHE II score and age. Placebo-treated patients with overt DIC had higher mortality than patients without (43 vs. 27%). DrotAA-treated patients with overt DIC had a trend towards greater relative risk reduction in mortality than patients without (29 vs. 18%, P = 0.261) but both groups had greater relative risk reduction than placebo-treated patients. Serious bleeding rates during DrotAA infusion in patients with and without overt DIC were slightly increased (P = 0.498), compared with placebo, while clinically overt thrombotic events during the 28-day period were slightly reduced (P = 0.144). Modified ISTH overt DIC scoring may be useful as an independent assessment for identifying severe sepsis patients at high risk of death with a favorable risk/benefit profile for DrotAA treatment. Patients without overt DIC also received significant treatment benefit.     

The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

Disseminated intravascular coagulation (DIC) is a frequently occurring complication of sepsis and may contribute to multiple organ failure. More insight into the pathogenesis of this derangement of the coagulation system is necessary to develop more effective therapeutic strategies for this condition. Recently, more detailed knowledge on the pathogenetic pathways involved in DIC has been obtained by the study of models of experimental bacteraemia and endotoxaemia in human subjects and non-human primates. The mechanisms that lead to activation of coagulation, potentiated by the simultaneous depression of physiological inhibitory systems and to impaired function of the fibrinolytic system, are outlined in this review. In addition, the mediatory role of various cytokines in the derangement of coagulation is discussed.     

The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia

Disseminated intravascular coagulation (DIC) is a frequently occurring complication of sepsis and may contribute to multiple organ failure. More insight into the pathogenesis of this derangement of the coagulation system is necessary to develop more effective therapeutic strategies for this condition. Recently, more detailed knowledge on the pathogenetic pathways involved in DIC has been obtained by the study of models of experimental bacteraemia and endotoxaemia in human subjects and non-human primates. The mechanisms that lead to activation of coagulation, potentiated by the simultaneous depression of physiological inhibitory systems and to impaired function of the fibrinolytic system, are outlined in this review. In addition, the mediatory role of various cytokines in the derangement of coagulation is discussed.     

Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

重度子痫前期孕妇凝血指标水平变化

目的分析重度子痫前期孕妇凝血指标水平的变化,探讨凝血功能异常与病情程度的关系。方法重度子痫前期孕妇（观察组）、正常待产孕妇（对照组）各64例,检测并比较2组凝血酶原时间（prothrombin time,PT）、PT百分活动度、凝血酶原国际标准化比值（International Normalized Ratio,INR）、活化部分凝血活酶时间（activated partial thromboplastin time,APTT）、纤维蛋白原（fibrinogen,FIB）、凝血酶时间（thrombintime,TT）、D-二聚体（D-dimer,D-D）、血小板计数;采用Shapiro-Wilk检验2组血小板计数分布范围。结果2组PT、PT百分活动度、INR、FIB、TT、D-D水平比较差异有统计学意义（P〈0.05）,APTT、血小板计数比较差异无统计学意义（P〉0.05）;观察组血小板计数分布范围较对照组增大,但差异无统计学意义（P〉0.05）。结论重度子疴前期孕妇凝血功能除出现异常高凝外,还可能合并继发性纤溶亢进。     

弥散性血管内凝血患者D-二聚体实验室检测分析

目的评价弥散性血管内凝血（DIC）患者体内D-二聚体水平,探讨DIC患者应用D-二聚体检查的临床价值。方法对该院收治的30例DIC患者（DIC组）及30例非DIC患者（对照组）进行D-二聚体检测,比较2组患者D-二聚体水平。同时按照DIC分期将30例DIC患者分为高凝期组、消耗性低凝期组及纤溶亢进期组,比较不同时期患者体内D-二聚体的水平并探讨两者间的相关性。结果 DIC组患者D-二聚体水平明显高于对照组患者,差异有统计学意义（t=11.229,P=0.000）,而纤溶亢进期患者体内D-二聚体水平最高,其次为消耗性低凝期,高凝期最低,差异有统计学意义（Z=-4.785,P=0.000）。同时DIC患者体内D-二聚体水平与DIC分期存在显著的正向直线相关关系（R=0.982,P=0.000）。结论 DIC患者体内D-二聚体水平明显高于非DIC患者,且DIC不同时期D-二聚体水平也存在差异,可用于对DIC患者病情的预测。     

儿童DIC前状态的实验研究

【目的】探索儿童DIC前状态诊断的实验指标。【方法】用发色底物法测定血浆抗凝血酶Ⅲ (AT Ⅲ ) ,用ELISA法测定血浆凝血酶 抗凝血酶Ⅲ复合物 (TAT)、组织因子 (TF)、组织因子途径抑制物 (TFPI)。【结果】在DIC组 (n =17) ,患儿TAT、TF含量显著升高 ,AT Ⅲ含量显著降低 ,FTPI含量稍降低 ,与正常对照组 (n =18)比较 ,TF、AT Ⅲ差异有显著性 (P <0 .0 1) ,TAT差异有显著性 (P <0 .0 5 ) ,而TFPI差异无显著性。在DIC前状态组 (n =2 8) ,患儿TAT、TF含量显著升高 ,AT Ⅲ含量显著降低 ,与正常对照组比较 ,差异有极显著性意义 (P <0 .0 1) ,TFPI差异无显著意义。在DIC组 ,AT Ⅲ、TAT、TF检测阳性率分别为 88.2 %、94 .1%、94 .1% ,敏感性高于其他常规实验指标。TFPI检测阳性率为 5 8.8%。在DIC前状态组AT Ⅲ、TAT、TF检测阳性率分别为 82 .1%、92 .9%、78.6 % ,敏感性高于其他常规实验指标。TFPI检测阳性率仅 10 .7%。【结论】分子标志物AT Ⅲ、TAT及TF能早期反映体内凝血及抗凝血系统的激活 ,在DIC特别是DIC前状态的诊断中有重要价值。