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.     

弥散性血管内凝血评分在脓毒症中的应用

目的 研究弥散性血管内凝血(DIC)评分系统与脓毒症患者病情评估及预后间的关系.方法 回顾性分析2005年1月-2008年12月本院重症监护病房(ICU)收治315例脓毒症患者的资料,按住院28 d的预后分为生存组(194例)与死亡组(121例).比较两组患者血小板计数(PLT)、纤维蛋白原(Fib)、凝血酶原时间(PT)及纤维蛋白单体的差异;用logistic单因素回归分析急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分、DIC评分与预后的关系,评价APACHEⅡ评分、DIC评分在脓毒症诊断中的价值.结果 死亡组PLT、Fib显著低于生存组,PT、活化部分凝血活酶时间(APTT)、凝血时间(ACT)和纤维蛋白单体值显著高于生存组,且APACHEⅡ评分、DIC评分显著高于生存组(P<0.05或P<0.01).APACHEⅡ评分、DIC评分与脓毒症预后间均呈显著正相关[DIC评分:χ2=17.741,P<0.001,优势比(OR)=1.413,95%可信区间(CI)为1.203～1.659;APACHEⅡ评分:χ2=36.456,P<0.001,OR=1.109,95%CI为1.072～1.147].APACHEⅡ评分曲线下面积(0.706)高于DIC评分曲线下面积(0.611).结论 APACHEⅡ评分、DIC评分均可作为脓毒症预后的预测指标,但DIC评分对脓毒症的诊断和预后判断价值低于APACHEⅡ评分.     

脓毒症合并弥漫性血管内凝血患者血清金属蛋白酶组织抑制剂的水平及诊断价值

目的 检测脓毒症及合并弥漫性血管内凝血(DIC)患者血清金属蛋白酶组织抑制剂(tissue inhibitor of metalloproteinase,TIMP)水平,并判断其对脓毒症患者发展成为DIC的预测诊断价值.方法 取60名患者,其中严重脓毒症患者28例(SS组),脓毒症合并DIC患者12例(SSD组),同期门诊体检者20例为对照组,收集临床及实验室参数,计算APACHEⅡ评分和DIC评分,采用酶联免疫吸附(ELISA)方法检测血清TIMP-1和TIMP-2的水平.结果 SS组患者血清TIMP-1水平(723.74±96.27)较对照组(574.24±79.99)明显升高(P＜0.05),TIMP-2水平(68.08±14.87)较对照组(89.99±18.45)明显降低(P＜0.05).SSD组患者血清TIMP-1水平(907.56±200.20)则较SS组升高明显(P＜0.05),而TIMP-2水平(44.84±22.13)也较SS组降低更明显(P＜0.05).相关分析显示TIMP-1主要与纤维蛋白原(FIB)呈负相关,差异具有统计学意义(P＜0.05),而与D-二聚体呈正相关,差异具有统计学意义(P＜0.05);血清TIMP-2则与血小板计数(PLT)、降钙素原(PCT)、DIC评分呈负相关,差异具有统计学意义(P＜0.05).ROC曲线图显示TIMP-1/TIMP-2的AUC=0.896,95％CI:0.843～0.950 (P＜0.05),较TIMP-1或TIMP-2的AUC更高.结论 脓毒症合并DIC患者的血清TIMP-1水平明显升高,主要影响纤溶系统;TIMP-2水平明显下降,主要影响血小板功能;TIMP-1/TIMP-2对脓毒症合并DIC的发生具有诊断价值.     

低分子肝素在弥散性血管内凝血患者的应用研究

目的研究低分子肝素应用于治疗弥散性血管内凝血(DIC)的临床疗效和安全性。方法将87例DIC患者按照治疗药物不同分为低分子肝素组和普通肝素组。观察监测凝血功能、疗效、28 d病死率以及不良反应。结果研究组治愈率以及有效率较对照组高,但差异无统计学意义,各症状的疗效也相当,但其对于部分凝血活酶(APTT)延长的影响更小,治疗后研究组APTT延长的患者数明显减少,而对照组治疗后APTT延长的患者数有所增高,研究组28 d死亡率与对照组相似,但出血例数更少。结论低分子肝素疗效与普通肝素相似,但出血等不良反应更少,更为安全有效。     

血浆置换在小儿弥散性血管内凝血的治疗作用

目的观察血浆置换在小儿弥散性血管内凝血治疗中的作用。方法选择临床确诊为小儿弥散性血管内凝血的患儿34例,在积极治疗原发病的基础上给予血浆置换治疗,观察血浆置换前后患儿的出血情况,凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、纤维蛋白原(Fib)、抗凝血酶Ⅲ(ATⅢ)及D-二聚体等指标变化。结果通过血浆置换治疗后,34例患儿出血情况减轻,除血小板变化不大外,PT、APTT及Fib明显改善,ATⅢ明显升高,D-二聚体明显降低。结论血浆置换在小儿弥散性血管内凝血的治疗中临床疗效显著。     

Preliminary study of microparticle coagulation properties in septic patients with disseminated intravascular coagulation

BackgroundSepsis typically results in enhanced coagulation system activation and microthrombus formation. Microparticle (MP) production promotes coagulation and enhances pro-coagulation. This study investigated how circulating MP levels and tissue factor-bearing MP (TF+-MP) activity caused coagulation in patients with septic disseminated intravascular coagulation (DIC).MethodsThirty patients with septic DIC and 30 healthy controls were studied from December 2017 to March 2019. Patient blood samples were collected at enrolment (day 1) and on days 3 and 5; DIC scores and Sequential Organ Failure Assessment (SOFA) scores were recorded. TF+-MP activity was measured using TF-dependent factor Xa generation experiments. Circulating MP concentrations were determined by MP capture assay. Clotting factor activity, antithrombin level, soluble thrombomodulin, and serum tissue factor pathway inhibitor (TFPI) concentrations were measured.ResultsPatients with septic DIC had lower circulating MP levels than healthy control patients. Circulating MP levels in patients with septic DIC were positively correlated with DIC scores and negatively correlated with coagulation factors, but TF+-MP activity did not correlate with clotting factor levels and TFPI.ConclusionsIn patients with septic DIC, circulating MP levels are important in promoting coagulation activation and increasing clotting factor consumption. TF+-MP activity may not be the main form of active TF.     

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。     

“龙参汤”合肝素治疗重度慢性阻塞性肺气肿并发弥散性血管内凝血疗效观察

目的：观察“龙参汤”合肝素治疗重度慢性阻塞性肺气肿并发弥散性血管内凝血（ＤＩＣ）的临床疗效。方法：６０例患者随机分为２组（各３０例）。２组患者均予常规综合治疗，对照组加用肝素治疗；治疗组则在对照组治疗基础上加用“龙参汤”。结果：治疗组和对照组临床总有效率分别为９６．６７％和８０．００％，２组比较有显著性差异（χ２＝４．０４３，Ｐ＜０．０５）；２组患者治疗后出凝血指标、动脉血气指标及血液流变性均有明显改善，治疗组又好于对照组。结论：“龙参汤”合肝素治疗重度慢性阻塞性肺气肿并发ＤＩＣ疗效更明显，值得临床进一步研究     

急性白血病并发弥散性血管内凝血患儿早期及干预后血凝指标变化

目的:探讨急性白血病(AL)患儿并发弥散性血管内凝血(DIC)早期及干预后血凝指标变化。方法:本实验分3组即健康对照组;AL组;AL并发DIC组,均于清晨抽取空腹血检测D-二聚体(DD)、纤维蛋白原水平(FBG)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及抗凝血酶-Ⅲ(AT-Ⅲ)。对AL并发DIC组患儿应用低分子肝素治疗,比较治疗前后各指标变化,采用SPSS10.0软件将各组进行统计学分析。结果:AL组与健康对照组比较,PT延长,FBG降低,DD明显升高,差异有统计学意义(P<0.05),AL并发DIC组与AL组比较,DD明显升高,AT-Ⅲ降低,差异有统计学意义(P<0.05),且与AL组相比,AL并发DIC组DD、AT-Ⅲ阳性率明显升高,且在DIC发病的不同临床阶段均保持在较高水平(80%以上),DD检测阳性率在血栓形成期高达100%。经肝素抗凝治疗后,AT-Ⅲ及FBG明显升高,DD降低,差异有统计学意义(P<0.05)。结论:AL并发DIC患儿存在凝血、纤溶系统的激活,AT-Ⅲ及DD可作为DIC早期诊断的指标,低分子肝素应用有助于改善DIC患儿的预后。     

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。     

Anticoagulant therapy for sepsis‐associated disseminated intravascular coagulation: the view from Japan

The current management of disseminated intravascular coagulation (DIC) is based on aggressive treatment of the underlying condition and resuscitation with appropriate blood products. Anticoagulant therapy has appeared and disappeared in the different guidelines and important documents detailing the treatment of DIC. For example, Surviving Sepsis Campaign (SSC) guidelines, the ‘global standard’ for the management of severe sepsis, had recombinant activated protein C highly recommended in the original version, but this was withdrawn in the latest version due to the lack of evidence. In contrast, recent international guidance released from the International Society on Thrombosis and Haemostasis has introduced the potential efficacy of other agents. In sepsis‐related DIC, the basis for anticoagulant therapy comes from the mounting evidence for the anti‐inflammatory effects which these agents possess and can prove beneficial in septic situations. Several studies have clearly shown the important cross‐talk between coagulation and inflammation in patients with sepsis. More recently, neutrophil extracellular traps and damage‐associated molecular patterns (DAMPs), especially histones, have been demonstrated to play a crucial role in the coagulopathy of sepsis. Once again, the natural anticoagulants have an important function in neutralizing the effects of DAMPs and histones. In this review, in addition to examining the important role of anticoagulants in the septic milieu, the clinical studies examining antithrombin, recombinant thrombomodulin and plasma‐derived activated protein C are detailed. However, large‐scale randomized controlled trials are yet to be performed, with important consideration of the timing, dosage and duration of treatment.     

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。     

Case of scrub typhus complicated by severe disseminated intravascular coagulation and death

Scrub typhus is an infectious disease that is caused by Orientia tsutsugamushi. The authors describe an autopsied case of scrub typhus complicated with severe disseminated intravascular coagulation (DIC). An 82‐year‐old man complained of fever 4 days after climbing a mountain. The patient was admitted to an urban hospital, and meropenem and ceftriaxone were administered. The patient's condition deteriorated and he was transferred to a second hospital. On physical examination, a black scab was found and scrub typhus was suspected. Despite intensive treatment, the patient died on the fifth day. High levels of O. tsutsugamushi IgM antibody were confirmed. An autopsy revealed systemic vasculitis and perivasculitis. The endothelial tissue of the white pulp of the spleen was markedly infiltrated by plasma cells. The authors speculated that a severe immune reaction against O. tsutsugamushi enhanced an inflammatory response, leading to DIC. This case is a warning to doctors who are not familiar with scrub typhus.     

D-dimer assay predicts mortality in critically ill patients without disseminated intravascular coagulation or venous thromboembolic disease

Objective: To determine if D-dimer predicts outcomes in critically ill patients. Design: Observational, cohort study. Setting: Medical intensive care unit (MICU) of a tertiary care hospital. Patients and participants: Seventy-four patients consecutively admitted to the MICU. Interventions: D-dimer was measured by latex agglutination within 12 h of admission to the MICU. Measurements and results: Of the study population, 43.2 % had positive D-dimers. The in-hospital mortality rate in D-dimer positive patients was 28.1 % as compared to 7.1 % in D-dimer negative subjects (p = 0.024). D-dimer positive patients had significantly greater frequencies of venous thromboses (21.9 % vs 4.8 %, p = 0.035). Conclusions: The D-dimer assay identifies patients at increased risk for mortality and may be a more sensitive test to determine the presence of underlying microvascular pathology in critically ill patients. A positive D-dimer at admission to the MICU is associated with an increased risk for the later development of a venous thromboembolic event (VTE). Received: 25 May 1998 Final revision received: 7 October 1998 Accepted: 9 December 1998     

小剂量低分子肝素治疗儿童急性早幼粒细胞白血病DIC的临床观察

目的:探讨小剂量低分子肝素治疗急性早幼粒细胞白血病弥漫性血管内凝血(DIC)的疗效及其安全性。方法:初次接受治疗的40例急性早幼粒细胞白血病(APL)患儿随机分成两组,小剂量低分子肝素治疗组(A组)20例,常规治疗组20例,比较两组的DIC发生率和完全缓解率。结果:低分子肝素治疗组DIC的发生率较常规治疗组低(P<0.05),而完全缓解率差异无统计学意义(P>0.05)。结论:小剂量低分子肝素可以有效减少急性早幼粒细胞白血病患儿DIC的发生,具有良好的安全性。     

分子标物及常规血凝学指标测定在DIC临床诊断中的价值对比分析

目的对比分析常见血凝学指标和几种血栓前状态分子标志物定量测定在DIC诊断中的价值.方法收集了30例正常人和63例DIC患者标本,根据DIC病程分为DIC早期(初发高凝血期)、中期(消耗性凝血障碍期)和晚期(继发性纤溶亢进期),测定了常规血凝学指标,并用ELISA法测定了血栓前状态分子标志物凝血酶原F1+2、凝血酶-抗凝血酶复合物(TAT)、栓溶二聚体(D-dimer,D-D)含量.结果各期DIC患者的部分常规血凝学指标有一定规律;而分子标志物变化不同.早期DIC中,D-D含量为(1.62±1.46)mg/L,NC组为(0.51±0.12)mg/L;F1+2含量为(4.96±2.78)nmol/L,NC组为(0.73±0.42)nmol/L;TAT含量为(33.11±20.59)μg/L,NC组为(1.64±3.04)μg/L;中期DIC中D-D含量为(6.85±8.37)mg/L;F1+2含量为(4.36±2.44)nmol/L,TAT含量为(22.53±20.98)μg/L;晚期DIC中D-D含量为(10.32±5.85)mg/L,F1+2的含量为(6.44±3.51)nmol/L,TAT含量为(36.64±20.09)μg/L.F1+2与TAT在所有DIC患者中有显著性相关(r=0.679,P＜0.0001),而F1+2与D-D、TAT与D-D无相关性.结论综合应用不同的血栓前状态分子标志物的定量测定和常用血凝学指标,不但有助于早期诊断DIC,并且可用于判断DIC的发展情况.