抗凝血酶Ⅲ预测脓毒症患者死亡的价值

目的分析脓毒症患者凝血功能与预后的关系,探讨抗凝血酶Ⅲ(antithrombinⅢ,AT-Ⅲ)活性预测脓毒症预后的临床价值。方法回顾性分析2018年6月1日至12月31日在我院重症医学科治疗的脓毒症患者62例,男37例,女25例,年龄22~88岁,根据确诊脓毒症后30 d内的死亡情况将患者分为两组:死亡组(n=21)和生存组(n=41)。收集患者性别、年龄、实验室检查等资料,比较两组确诊脓毒症当天的外周静脉血AT-Ⅲ、凝血指标[D-2聚体(D-D)、纤维蛋白降解产物(FDP)、纤维蛋白原(FIB)、凝血酶时间(TT)、活化部分凝血酶原时间(APTT)、国际标准化比值(INR)、凝血酶原时间(PT)]、C反应蛋白(CRP)、Plt等。结果死亡组AT-Ⅲ活性明显低于生存组[(57.3±16.9)%vs(76.1±21.1)%,P<0.001]。AT-Ⅲ是脓毒血症患者死亡预后的独立预测因素(OR=0.949,95%CI 0.917~0.982,P=0.03)。AT-Ⅲ预测脓毒症患者死亡预后的ROC曲线下面积为0.748(95%CI 0.621~0.875,P<0.001),以AT-Ⅲ值62.0%为临界值,其预测的敏感度为78.0%,特异度为61.9%。结论脓毒症早期抗凝血酶Ⅲ活性的降低可能预示着预后不良,抗凝血酶Ⅲ作为早期评估脓毒症严重程度的指标对临床具有重要的指导意义。     

静脉血栓栓塞症患者血清AT3、蛋白C、蛋白S水平临床分析

目的检测静脉血栓栓塞症（VTE）患者血清中抗凝血酶（AT3）、蛋白C（PC）、蛋白S（Ps）水平,分析其与VTE的关系。方法回顾性分析251例VTE患者性别、年龄特点及血清中AT3、PC、PS的水平,并与60例正常人血样进行对比。结果251例VTE患者中,男94例,女157例,男：女=1．11：1．4,中位年龄43（5～81）岁。AT3、PC、PS三者均有不同程度降低,其中AT3占15．14％（38例）,Pc占10．36％（26例）,PS占20．3％（51例）。结论血浆AT3、PC、PS缺陷是促发VTE的重要原因,检测其水平变化对静脉血栓栓塞症的预防、诊断及治疗有指导意义。     

血液学指标对复发脑梗死的诊疗价值

目的探讨血液学指标对预测脑梗死复发的价值,为缺血性脑血管病的二级预防开辟新的思路。方法将200例急性脑梗死患者根据头颅MRI结果分为首发性脑梗死组（FIS）109例,复发性脑梗死组（RIS）91例。记录其复发的危险因素,如年龄、吸烟、高血压、糖尿病、高脂血症等,同时于发病72h内测定d-二聚体、蛋白S、蛋白C、抗凝血酶Ⅲ、血栓调节蛋白（TM）、组织型纤溶酶原激活物（t—PA）、组织型纤溶酶原激活物抑制物、同型半胱氨酸（Hcy）以及抗心磷脂抗体等9项血液学指标。结果①RIS组患者平均年龄为（59±9）岁,FIS组患者为（56±10）岁;RIS组患者合并高血压的比率（83．5％）明显高于FIS组（71．6％）。②与FIS组患者相比,RIS组患者血液学指标紊乱严重,9项中有6项表现出明显的差异：蛋白s在RIS和FIS组分别为（23±7）μg/ml、（25±6）μg/ml,P=0．002;蛋白C在RIS和FIS组分别为（4．5±1．5）μg/ml、（4．9±1．7）μg/ml,P=0．05,显示蛋白S和蛋白C在RIS组降低。RIS组TM增高[（30±13）μg/L、（26±7）μg/L,P=0．01];RIS组t—PA较FIS组增多[（7．6±3．0）斗μg/L、（6．7±2．6）μg/L,P=0．025]。RIS组患者血浆Hcy浓度[（23±10）μmol／L]较FIS组[（17±6）μmol／L]升高,P〈0．01。RIS组患者抗心磷脂抗体IgG（ACAIgG）阳性的比例比FIS组高（18．7％、5．5％,P=0．004）。③多因素Logistic回归分析显示,高血压（OR=2．050;95％CI：1．53～6．53）、高龄（OR=1．025;95％CI：1．00～1．05）、蛋白C降低（OR=0．692;95％CI=0．54～0．88）、高同型半胱氨酸血症（OR=1．074;95％CI：1．03～1．12）以及抗心磷脂抗体IgG阳性（OR=3．426;95％CI：1．19～9．84）是预测脑梗死复发的独立危险因素。结论血液学指标失衡可增加脑梗死复发风险,定期检测血液学相关指标有助于早期预测脑梗死的复发。     

Sustained bleeding from bites of hatchling leeches

Prolongation of haemostatic parameters in the host achieved by hatchlingHirudo medicinalis differs quantitatively but not qualitatively from those achieved by adult leeches. The duration and the rate of blood loss from the bite wounds, the gain in body weight of leeches and the duration of feeding each increase with successive feeding episodes. The mean duration of bleeding from bite wounds of hatchling leeches feeding for the first time on human volunteers was 43 min compared to 6 min from control incisions and 600 min in adult leeches. The mean ‘whole body’ concentration of hirudin in 2-week-old hatchlings was 10 antithrombin units (AT-U) compared to 285 AT-U in the head of each adult leech.     

失血性休克模型中纤溶功能和抗凝血酶活性的变化研究

目的探讨大鼠失血性休克模型中纤维蛋白溶解功能(纤溶功能)和抗凝血酶活性的动态变化及意义。方法采用40只成年Sprague Daw ley(SD)大鼠,通过快速放血使其处于休克状态,随机分为8组:休克前组、休克1 h组、休克2 h组、休克4 h组、休克6 h组、休克8 h组、休克12 h组和休克24 h组,每组各5只。观察血浆组织型纤溶酶原激活物抗原(tPA:Ag)、纤溶酶原激活物抑制剂-1抗原(PAI-1:Ag)、纤维蛋白(原)降解产物(FDP)、D-二聚体(DD)含量、纤维蛋白原(FIB)含量、纤溶酶原活性(PLG:A)及血浆抗凝血酶活性(AT:A)的动态变化。结果与休克前比较,各休克组PLG:A、AT:A逐渐降低,于休克后2 h均显著降低(P<0.01)。休克后血浆tPA:Ag和PAI-1:Ag、FDP、DD增加(P<0.01),分别于休克后2～8 h达到峰值,随后tPA:Ag随休克的时间延长逐渐降低。血浆FIB于休克1 h明显增加(P<0.01),随着休克的发展,于休克2 h开始下降,休克12 h降至最低值。结论在失血性休克过程中早期纤溶功能亢进,而后趋向受抑状态,抗凝血酶呈消耗性下降,纤溶和抗凝系统失衡在休克的发生、发展过程中具有重要作用。     

脓毒症继发急性肾损伤过程中的凝血变化

目的 脓毒症继发急性损伤是脓毒症患者死亡的重要原因之一,凝血变化是急性肾损伤重要因素。本研究旨在筛选脓毒症过程中同急性肾损伤相关的凝血指标。方法 本研究收集外科、急诊及呼吸重症监护室的脓毒症患者,纳入132例脓毒症患者,其中合并急性肾损伤64例,非急性肾损伤68例。收集各组患者一般资料及入ICU第1个24h内各项实验室指标,利用Logistic回归分析及Cox回归分析进行统计学分析。结果 AKI组与非AKI组相比,抗凝血酶Ⅲ(P=0.007)显著降低,D-二聚体则显著升高(P=0.006)。二分类变量Logistic回归显示,D-二聚体与抗凝血酶Ⅲ为脓毒症继发AKI的危险因素,OR值分别为3.018(95%CI:1.127～8.083)和2.89(95%CI:1.181～7.070),P<0.05。利用Cox回归分析显示仅有D-二聚体同病死率相关,HR值1.347(95%CI:1.081～1.677),P=0.008。结论 D-二聚体和抗凝血酶Ⅲ是脓毒症继发AKI发生的独立危险因素。D-二聚体升高同脓毒症继发AKI的28d病死率高相关。     

Anticoagulant therapy by continuous heparin-abtithrombin III infusion in newborns with disseminated intravascular coagulation

In ten newborns with severe alteration of the coagulation system due to DIC, AT III concentrate was infused continuously after prior activation with heparin. The rise in AT III activity showed a great variability among the infants and for one child during the course of the therapy. The mean rise of AT III activity by 40 U/kg per day heparin was 8.7%. If AT III concentrate (40 U/kg per day) was activated with 200 U/kg per day heparin, excessive anticoagulatory effect was only observed in one child. In four children who had failed to respond to prior heparin therapy, improvement of the coagulation status was achieved within 2 days.Abbreviations DIC disseminated intravascular coagulation - AT III antithrombin III     

Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (fondaparinux)

Fondaparinux (Arixtra) is the first of a new class of selective indirect antithrombin-dependent factor Xa inhibitors, which inhibits thrombin generation. Fondaparinux is a completely synthetic pentasaccharide. It is a single molecular entity with a well-defined pharmacological target. Fondaparinux has nearly complete bioavailability after subcutaneous injection. The pharmacokinetics of fondaparinux appears predictable and consistent. The peak plasma level is obtained about 2 h after the subcutaneous injection, indicating that a rapid onset of antithrombotic activity is obtained on initiation of treatment. The elimination half-life is about 17 h and it is dose-independent, which allows a convenient once-daily dosing regimen. Fondaparinux is eliminated exclusively by the kidneys. Thus, the estimation of the renal function especially in elderly patients is important for the treatment with fondaparinux, whereas it is contraindicated in patients with severe renal insufficiency. Phase II clinical studies have identified a subcutaneous dose of 2.5 mg once daily for prophylaxis of venous thromboembolism in patients undergoing major orthopaedic surgery. Four phase-III clinical trials using bilateral phlebography for the diagnosis of DVT, demonstrated a combined 50% relative risk reduction of asymptomatic venous thromboembolic events in orthopaedic surgery patients in comparison to the low-molecular-weight heparin (LMWH) enoxaparin. Hemorrhagic complications for fondaparinux were either comparable or higher than those for LMWH but the authors did not judge that the increased bleeding was clinically relevant. A dose ranging study led to the selection of the dose of 7.5 mg at a single daily subcutaneous injection as optimal for the treatment of VTE. In two phase III clinical trials, the dose of 7.5 mg/day is expected to be as efficacious and safe as heparin for the treatment of DVT or PE, respectively. Phase II studies show that the efficacy-to-safety ratio of fondaparinux in the treatment of unstable angina or as an adjunct to thrombolysis in acute myocardial infarction is promising. These results demonstrated that a single anti-Xa agent devoid of antithrombin activity is a potent antithrombotic drug. Fondaparinux has obtained FDA and European health authorities approval. Its use on a large scale will allow the evaluation of its efficacy and tolerance in the daily clinical practice. Chemical modifications of the original synthetic pentasaccharide increase the affinity to AT resulting in a more potent inhibition of FXa and longer half-life. Idraparinux is the first of these new oligosaccharides that we named "meta-pentasaccharides." After subcutaneous injection the half-life of idraparinux is about 80 h allowing a single injection per week. A dose-finding study has established the optimal dose given once a week to be compared with warfarin for the treatment of DVT.     

Antithrombin III prevents deleterious effects of remote ischemia-reperfusion injury on healing of colonic anastomoses

BACKGROUND: Antithrombin III is known as the most important natural inhibitor of thrombin activity and has been shown to attenuate local harmful effects of ischemia-reperfusion injury in many organs. In recent animal studies, delaying effect of remote organ ischemia-reperfusion injury on healing of intestinal anastomoses has been demonstrated. In this study, we investigated whether antithrombin III reduces deleterious systemic effects of ischemia-reperfusion injury on healing of colonic anastomoses in rats. METHODS: Anastomosis of the left colon was performed in 24 rats that were divided into three groups: sham operated control (group I, n = 8), 30 minutes of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II, n = 8), antithrombin III treated group (250 U/kg before and after the ischemia-reperfusion, group III, n = 8). On postoperative day 6, all animals were sacrificed, and bursting pressure and tissue hydroxyproline content of the anastomoses were assessed and compared. RESULTS: On postoperative day 6 the mean bursting pressures were 149.6 +/- 4.8, 69.8 +/- 13.5, and 121.8 +/- 8.7 mm Hg for groups I, II, and III, respectively (P = 0.000). Mean tissue hydroxyproline concentration values were 389.5 +/- 29.6, 263.1 +/- 10.0, and 376.0 +/- 33.8 microg/mg for groups I, II, III respectively (P = 0.005). CONCLUSIONS: This study showed that, antithrombin III treatment significantly prevented the delaying effect of remote organ ischemia-reperfusion injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether antithrombin may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where remote organ ischemia-reperfusion injury takes place.