Prognostic values of the factor Xa-activated clotting time and endogenous thrombin potential in patients suspected of having disseminated intravascular coagulation

Background

Widespread coagulation activation and intravascular fibrin formation are clinical features of disseminated intravascular coagulation (DIC). The endogenous thrombin potential (ETP) has been shown to be a useful marker for hypo- or hypercoagulability. The factor Xa-activated clotting time (XACT) represents plasma levels of procoagulant phospholipids. We investigated whether the ETP and XACT would be good prognostic markers in patients suspected of having DIC and whether these markers would show a significant correlation with the thrombin-antithrombin complex (TAT), a marker of in vivo coagulation activation.

Methods

One hundred twenty-nine patients suspected of having DIC were enrolled for the study. The TAT was measured by ELISA. The ETP and XACT were measured by calibrated automated thrombinography. The 28-day mortality was used as a predictor of clinical outcomes.

Results

In overt DIC, higher XACT (9.67 vs. 7.33 min) and higher TAT (26.15 vs. 11.56 ng/ml) results were obtained from the nonsurvivors than from the survivors. ETP levels were lower in the overt DIC group than in the no overt DIC group. In receiver operating characteristic analysis, which was conducted to predict the 28-day mortality, the areas under the receiver operating characteristic analysis curve were as follows: 0.71 (95% CI: 0.62-0.78) for the XACT, 0.70 (0.61-0.77) for the TAT, and 0.64 (0.55-0.72) for the ETP. For the diagnosis of overt DIC, the area under the curve of XACT, TAT and ETP were 0.77 (0.69-0.84), 0.64 (0.55-0.72) and 0.73 (0.64-0.80), respectively. The odds ratio of the XACT for the relative risk of 28-day mortality was 9.60 (3.53-26.11), and that of the TAT was 5.18 (2.11-12.72) and that of the ETP 7.66 (1.67-35.17). For the diagnosis of overt DIC, the odds ratio of XACT, TAT and ETP were 37.35 (4.86-286.89), 4.89 (1.93-12.43) and 4.89 (1.98-12.09), respectively. There was a negative correlation between the TAT and ETP (r = − 0.223, P = 0.012) and a positive correlation between the TAT and XACT (r = 0.251, P = 0.004).

Conclusion

Our results suggest that the XACT and ETP may be useful diagnostic and prognostic markers for the DIC. Among various markers, the XACT serves as a good prediction of the 28-day mortality in patients suspected of having DIC.     

中期妊娠并发胎盘早剥及弥漫性血管内凝血1 例报告

1临床资料患者36岁,孕2产1,因“停经22周,胎动消失2 d,牙龈出血7 h”于2008年11月13日4:55急诊入院。患者末次月经2008年5月27日,未产检,入院前2 d开始未觉胎动,未重视,入院前1 d夜间无明显诱因出现牙龈出血,后来我院急诊就诊,超声示:无胎心搏动,胎盘位于右前壁,胎盘内低至无回声区。血常规:WBC 15.11×109/L,Hb 100 g/L,PLT 92×109/L。凝血功能:PT＞180 s,APTT＞109 s。拟诊“死胎、胎盘早剥、弥漫性血管内凝血（DIC）？”,即收住入院。患者曾于1996年平产1胎,有“肾结石”病史2年,平素口服中药治疗,否认高血压病史。入院体格检查:体温36.7℃,脉搏80次/min,呼吸20次/min,血压125/83 mmHg(1 mmHg=0.133 kPa),宫底脐上4指,轻压痛,腹肌略紧张,宫缩规律（30 s/2 min）,强度中弱。入院后复查血常规:WBC 16.74×109/L、Hb 92 g/L、PLT 75×109/L。凝血功能:PT＞120 s、APTT＞180 s、FDP＞129 μg/ml。超声示:无胎心,双顶径6.1 cm,胎盘上方见11.6 cm×6.9 cm回声不均区。诊断:死胎、胎盘早剥、DIC。立即报病危,予吸氧,补充血容量,完善备血、血小板、冷沉淀等术前准备,急诊行全麻下剖宫取胎术,术中见子宫增大如孕5个半月大小,两侧宫角处呈紫蓝色,切开子宫下段,宫腔内大量不凝血涌出,迅速徒手取出胎儿及胎盘组织,检查胎盘80%面积见凝血块压迹。术中见胎盘剥离面及子宫切口广泛渗血,宫缩尚可,术中以试管法取静脉血5 ml,轻叩管壁,15 min后仍不凝,术中复查血常规:WBC 14.34×109/L、Hb 75 g/L、PLT 48×109/L。交替输注纤维蛋白原2 g,冷沉淀20 U,血小板10 U,红细胞悬液及血浆1 200 ml,并按摩子宫、应用促宫缩药物及缝扎止血,组织渗血情况好转,宫缩好,腹腔留置引流管1根后关腹。宫腔内积血及术中出血共约800 ml,术后转ICU监护2 d,抗生素预防感染,输血及冷沉淀改善凝血功能,低分子肝素改善循环功能,呋塞米利尿及对症治疗,术后2 d各项指标基本恢复正常。术后第8天,患者恢复良好出院,出院前复查血常规Hb 131 g/L、PLT 202×109/L,凝血功能:PT 25.6 s、APTT 28.9 s、FDP 11.63 μg/ml。出院诊断:孕22周,G2P1,死胎;胎盘早剥（重度）;DIC。     

Fresh-frozen plasma and platelet transfusions are associated with development of acute lung injury in critically ill medical patients

BACKGROUND: Transfusion has long been identified as a risk factor for acute lung injury (ALI)/ARDS. No study has formally evaluated the transfusion of specific blood products as a risk factor for ALI/ARDS in critically ill medical patients. METHOD: In this single-center retrospective cohort study, 841 consecutive critically ill patients were studied for the development of ALI/ARDS. Patients who received blood product transfusions were compared with those who did not, in univariate and multivariate propensity analyses. RESULTS: Two hundred ninety-eight patients (35%) received blood transfusions. Transfused patients were older (mean [+/- SD] age, 67 +/- 17 years vs 62 +/- 19 years; p < 0.001) and had higher acute physiologic and chronic health evaluation (APACHE) III scores (74 +/- 32 vs 58 +/- 23; p < 0.001) than those who had not received transfusions. ALI/ARDS developed more commonly (25% vs 18%; p = 0.025) in patients exposed to transfusion. Seventeen patients received massive RBC transfusions (ie, > 10 U of blood transfused within 24 h), of whom 13 also received fresh-frozen plasma (FFP) and 11 received platelet transfusions. When adjusted for the probability of transfusion and other ALI/ARDS risk factors, any transfusion was associated with the development of ALI/ARDS (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.24 to 3.75). Among those patients receiving individual blood products, ALI/ARDS was more likely to develop in patients who received FFP transfusions (OR, 2.48; 95% CI, 1.29 to 4.74) and platelet transfusions (OR, 3.89; 95% CI, 1.36 to 11.52) than in those who received only RBC transfusions (OR, 1.39; 95% CI, 0.79 to 2.43). CONCLUSION: Transfusion is associated with an increased risk of the development of ALI/ARDS in critically ill medical patients. The risk is higher with transfusions of plasma-rich blood products, FFP, and platelets, than with RBCs.     

Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth

BACKGROUND & AIMS: Increased inflammatory cytokine levels and intestinal epithelial cell apoptosis leading to disruption of epithelial integrity are major pathologic factors in inflammatory bowel diseases. The probiotic bacterium Lactobacillus rhamnosus GG (LGG) and factors recovered from LGG broth culture supernatant (LGG-s) prevent cytokine-induced apoptosis in human and mouse intestinal epithelial cells by regulating signaling pathways. Here, we purify and characterize 2 secreted LGG proteins that regulate intestinal epithelial cell antiapoptotic and proliferation responses. METHODS: LGG proteins were purified from LGG-s, analyzed, and used to generate polyclonal antibodies for immunodepletion of respective proteins from LGG-conditioned cell culture media (CM). Mouse colon epithelial cells and cultured colon explants were treated with purified proteins in the absence or presence of tumor necrosis factor (TNF). Akt activation, proliferation, tissue injury, apoptosis, and caspase-3 activation were determined. RESULTS: We purified 2 novel proteins, p75 (75 kilodaltons) and p40 (40 kilodaltons), from LGG-s. Each of these purified protein preparations activated Akt, inhibited cytokine-induced epithelial cell apoptosis, and promoted cell growth in human and mouse colon epithelial cells and cultured mouse colon explants. TNF-induced colon epithelial damage was significantly reduced by p75 and p40. Immunodepletion of p75 and p40 from LGG-CM reversed LGG-CM activation of Akt and its inhibitory effects on cytokine-induced apoptosis and loss of intestinal epithelial cells. CONCLUSIONS: p75 and p40 are the first probiotic bacterial proteins demonstrated to promote intestinal epithelial homeostasis through specific signaling pathways. These findings suggest that probiotic bacterial components may be useful for preventing cytokine-mediated gastrointestinal diseases.     

肺癌患者口服易瑞沙诱发DIC1例报告

1病例报告患者,女,66岁。头晕头疼2月,伴左侧胸背部疼痛。于2008年4月无明显诱因出现头晕,伴头部闷胀疼痛不适,无明显恶心、呕吐,无咳嗽、咯血、发热,伴左侧胸背部间断性疼痛,2008年5月18日于外院就诊,肺部CT示"右肺下叶占位性病变,双侧胸腔少量积液,纵隔淋巴结肿大"。CA125349.25u/ml,肝胆脾、腹膜后、肾上腺、子宫附件B超"未见明显异常"。体检发现,右锁骨上可及3cm×2cm大小肿大     

Biotransformation and in vitro assessment of metabolism-associated drug–drug interaction for CRx-102, a novel combination drug candidate

CRx-102 is an oral synergistic combination drug which contains the cardiovascular agent, dipyridamole (DP) and a very low dose of the glucocorticoid, prednisolone (PRED). CRx-102 works through a novel mechanism of action in which DP selectively amplifies the anti-inflammatory activity of PRED without replicating its side effects. CRx-102 is in clinical trials for the treatment of osteoarthritis. Here we delineate the in vitro metabolism and explore the potential for a drug–drug interaction between the active agents in CRx-102. Our study using human hepatocyte suspensions showed that both DP and PRED were metabolized by CYP3A4 isozymes, resulting in the formation of diverse arrays of both oxidative and oxidative-reduced metabolites. Within phase 1 biotransformation, CYP3A4 was one of the pathways responsible for the metabolism of PRED, while phase 2 biotransformation played a significant role in the metabolism of DP. Glucuronidation of DP was substantial and was catalyzed by many UGT members, specifically those in the UGT1A subfamily. Based on the tandem mass (MS/MS) product ion spectra (PIS) acquired, the major metabolites of both agents, namely, monooxygenated, mono-N-deethanolaminated, dehydrogenated and O-glucuronidated metabolites of DP and the monooxygenated (e.g., 6-hydroxyl), dehydrogenated (prednisone) and reduced (20-hydroxyl) metabolites of PRED, were identified and elucidated. The affinities for DP biotransformation, including CYP3A4-mediated oxidative pathways and UGT-mediated O-glucuronidation, appeared high (K_m < 10 μM), as compared with the modest affinities of PRED biotransformation catalyzed by CYP3A4 (K_m ∼ 40–170 μM). DP, but not PRED, exerted a minimal inhibitory effect on the drug-metabolizing CYP isoforms, including CYP3A4, which was determined using a panel of CYP isoform-preferred substrate activities in pooled human liver microsomal (HLM) preparations and microsomal preparations containing the recombinant enzymes (K_i ∼ 2–12 μM). Using the DP maximal plasma concentration (C_max) observed in the clinic and a predictive mathematical model for metabolism-associated drug–drug interaction (DDI), we have demonstrated that there is little likelihood of a pharmacokinetic interaction between the two active agents in CRx-102.     

32例产妇产后出血分析

目的对产后出血的病因、治疗及并发症进行分析,提高对产后出血的认识和处理能力。方法对我院2005年10月～2007年4月间的32例产后出血病例进行回顾性分析。结果宫缩乏力性子宫出血仍占产后出血的首位,为8121％;剖宫产产后出血率171％;阴道分娩产后出血发生率为124％,两者无明显差异。结论产后出血的主要原因是宫缩乏力,合理的选择剖腹产术,积极控制并发症,及正确处理第三产程可以减少产后出血的发生。对保守治疗无效的产后出血,应果断地行子宫切除术,以抢救病人的生命。     

纤溶指标对弥漫性血管内凝血的诊断价值

[目的]探讨弥漫性血管内凝血(DIC)敏感性和特异性较高的诊断指标应用于临床。[方法]选用BPC、PT、Fbg、APTT、DIC过筛诊断指标,3P、D-D二聚体、TT、FDP、ELT、ATⅢC、α2MG、VWFAg、乙醇胶、红细胞碎片确诊诊断指标,对1629例DIC各期病人及正常对照组进行检测比对分析,找出相关性。[结果]DIC前状态最敏感的指标是3P、ATⅢC、VWFAg,异常率高达100%;其次D-D二聚体,异常率为98.5%;BPC、PT、APTT半数以上异常,Fbg仅有1/3异常,其余各项指标敏感性较差;在消耗性低凝期VWFAg异常率持续增高,BPC、PT、TT异常率明显升高,而3P、ATⅢC、α2MG仅呈不同程度的增加;纤溶凝衰期时,FDP、ELT、D-D二聚体、红细胞碎片异常率高达100%,其他各项指标均有不同的异常改变。[结论]纤溶指标3P、D-D二聚体、ATⅢC可做DIC高凝前状态的诊断指标,BPC、PT、Fbg、VWFAg可做DIC过筛诊断指标,纤溶指标D-D二聚体、FDP、ELT、α2MG红细胞碎片可做DIC纤溶凝衰期诊断指标。因此,纤溶指标对DIC早期诊断及分型确诊诊断有重要实用价值。     

重度胎盘早剥的处理时限与妊娠结局

目的探讨重度胎盘早剥的诱因、出现症状至分娩的时间与妊娠结局的关系、并发症的处理。方法回顾性分析北京航天总医院2002年1月至2009年12月44例重度胎盘早剥的临床资料。结果主要诱因为妊娠高血压疾病、胎膜早破,并发子宫胎盘卒中27例（61.4%）、休克19例（43.2%）、DIC13例（29.5%）、围产儿死亡23例（52.3%）。27例子宫胎盘卒中自出现症状至分娩时间为6h5min±4h12min;18例失血性休克为6h35min±3h49min;13例DIC为7h2min±4h12min。结论早期诊断及正确处理是减少并发症,降低围产儿死亡率的关键。     

Severe community-acquired pneumonia, shock and multiorgan dysfunction syndrome caused by Chlamydia pneumoniae

Chlamydia pneumoniae has been increasingly recognized as an important aetiological agent in community-acquired pneumonia. A case of severe community-acquired pneumonia and multifunction dysfunction syndrome resulting from Chlamydia pneumoniae infection in a previously healthy adult is presented.