以凝血功能障碍为首发表现的特发性成人肝内胆管缺失症1例

<正>病例:患者男,24岁。因"反复皮下瘀斑8年,身目黄染3个月"于2012年3月11日收治入院。患者8年前四肢受到轻微碰撞后出现大面积皮下瘀斑伴牙龈出血,外院予止血治疗(具体不详)后瘀斑消退,但该症状常反复。1年前再次因皮下瘀斑至外院就诊,检查显示凝血酶原时间(PT)120 s,活化部分凝血活酶时间(APTT)107.8 s,凝血因子FⅦ、FⅨ下降,ALT 372 U/L,AST 386 U/L,ALP 1 633 U/L,甲状旁腺素173.9 pg/mL,骨扫描未见异常,骨髓穿刺活检提示刺激性骨髓象,予"止血、护肝"等对症治疗,皮下出血症状好转后出院。11个月前,复查ALT 298 U/L,AST 246 U/L,继续     

Hot topics in coagulation testing: Important considerations for testing children for bleeding/thrombotic disorders

The accurate use and interpretation of diagnostic investigations are essential for safe and effective patient care. Appropriate application and interpretation of coagulation testing can be challenging, and many controversies exist relating to the standardization of testing procedures, the application of relevant tests to different patient populations and the interpretation of test results. We present a list of the most prominent controversies in coagulation testing and have selected three specific examples (age‐appropriate reference ranges, therapeutic anticoagulation monitoring and tests of thrombin generation) for closer discussion, highlighting examples with a paediatric framework. We discuss the limitations of discrete age‐partitioned reference intervals, given the established principle of developmental haemostasis; the difficulties in establishing normative data across different laboratories; important pre‐analytical variables affecting coagulation testing; the challenges in interpreting APTT and anti‐Xa assays for monitoring unfractionated heparin therapy in different clinical situations; and the limitations in interpreting tests of thrombin generation due to current available thrombin‐specific substrates and the complicating factor of variable alpha2‐macroglobulin levels. These controversies are demonstrated using paediatric examples, but raise important implications for coagulation testing in patients of all ages and highlight the pressing need for further research in these areas.     

血栓弹力图在妊娠合并血小板减少症患者中的应用

目的探讨血栓弹力图(thromboelastography,TEG)在妊娠合并血小板减少症患者(PAT)中的应用。方法收集我院2016年4月～2019年3月确诊的60例妊娠合并血小板减少症患者,按照1∶1比例配对法分为两组,对照组30例,行常规凝血功能检测;观察组30例,进行常规凝血功能检测及血栓弹力图检测评估,分析两组的分娩情况、术中术后出血情况及实验室指标检测结果。结果两组ALT、AST、PT、APTT、TT、FIB无明显差异(P0.05),观察组阴道分娩率高于对照组、术中出血量高于对照组(P0.05),但两组的术后出血量及产后大出血发生率无差异(P0.05)。结论血栓弹力图用于PAT患者凝血的监测,可评估出血风险,为分娩方式的选择提供指导依据。     

老年重型胰腺炎患者机体凝血和抗凝系统的变化情况

目的探讨老年重型胰腺炎患者机体内凝血和抗凝系统的变化情况,分析凝血、抗凝指标对疾病发展程度的意义。方法收集2009年10月-2013年10月湖北医药学院附属太和医院收治的重型胰腺炎老年患者44例作为观察组,同期选择健康人群24例作为对照A组,同期选择老年轻型胰腺炎患者24例作为对照B组,对三组入选受试者进行血液样本采集,检测和记录标本凝血酶原时间(PT)、部分活化凝血酶原时间(APTT)、纤维蛋白原(FIB)D-二聚体。结果观察组PT、APTT、FIB和D-二聚体均明显高于对照A组和对照B组(P0.05)。结论老年重型胰腺炎患者机体内的凝血和抗凝系统明显异于常态时,可以直接影响到正常的微循环,同时凝血和抗凝系统指标患者病情发展的程度,有助于评估。     

Carbon monoxide: Anticoagulant or procoagulant?

Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis. Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α₂-antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide. Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be species specific differences with regard to hemostatic response to carbon monoxide. Carbon monoxide may be a Janus-faced molecule, with potential to attenuate or exacerbate thrombophilic disease.     

Alpha-1 proteinase inhibitor M358R reduces thrombin generation when displayed on the surface of cells expressing tissue factor

The M358R variant of alpha-1-proteinase inhibitor (API) is a potent soluble inhibitor of thrombin. Previously we engineered AR-API M358R, a membrane-bound form of this protein and showed that it inhibited exogenous thrombin when expressed on transfected cells lacking tissue factor (TF). To determine the suitability of AR-API M358R for gene transfer to vascular cells to limit thrombogenicity, we tested the ability of AR-API M358R to inhibit endogenous thrombin generated in plasma via co-expression co-expressing it on the surface of cells expressing TF. Transfected AR-API M358R formed inhibitory complexes with thrombin following exposure of recalcified, defibrinated plasma to TF on T24/83 cells, but discontinuously monitored thrombin generation was unaffected. Similarly, AR-API M358R expression did not reduce continuously monitored thrombin generation by T24/83 cell suspensions exposed to recalcified normal plasma in a Thrombogram-Thrombinoscope-type thrombin generation assay (TGA); in contrast, 1 μM hirudin variant 3 or soluble API M358R abolished thrombin generation. Gene transfer of TF to HEK 293 conferred the ability to support TF-dependent thrombin generation on HEK 293 cells. Co-transfection of HEK 293 cells with a 9:1 excess of DNA encoding AR-API M358R to that encoding TF reduced peak thrombin generation approximately 3-fold compared to controls. These in vitro results suggest that surface display of API M358R inhibits thrombin generation when the tethered serpin is expressed in excess of TF, and suggest its potential to limit thrombosis in appropriate vascular beds in animal models.     

Association of hemodilution and blood pressure in uncontrolled bleeding

Background

Hemodynamic status and coagulation capacity affect blood loss after injury. The most advantageous fluid and blood pressure to optimize resuscitation and minimize perturbation of coagulation are unclear. We investigated interactions of isovolumic hemodilution on hemodynamics, coagulation, and blood loss after injury.

Methods

Twenty-five male rats were randomized into three groups (Whole Blood Uncontrolled Blood Pressure [WBU], n = 7; Lactated Ringers Uncontrolled Blood Pressure [LRU], n = 10; Whole Blood Controlled Blood Pressure [WBC], n = 8) with isovolumic hemodilution of 50% blood volume, with and without control of pre-injury blood pressure. All rats underwent uniform grade IV liver injury 30 min after serial exchanges. Post-injury blood loss and coagulation function were measured.

Results

Dilution occurred, determined by hematocrit, with LRU having a greater reduction. Pre-injury mean arterial pressure (MAP) decreased compared with baseline (98 ± 7 mmHg) with LRU (62 ± 14 mmHg) and WBC (61 ± 10 mmHg), resulting in WBU (101 ± 13 mmHg) being significantly higher and not changed from baseline. Post-injury, MAP decreased from pre-injury, with LRU significantly lower than the other two groups. No differences were observed in prothrombin time/international normalized ratio or thromboelastography. Bleed volume was significantly different between groups: WBU < WBC < LRU and associated with the pre-injury MAP. Controlling baseline MAP, dilution with Lactated Ringers (LR) resulted in greater blood loss than whole blood (3.0 ± 0.4 versus 1.9 ± 0.3 mL).

Conclusions

In this rat model of liver injury, blood loss was associated with baseline MAP and type of fluid used for dilution. Hemodilution with LR did not produce coagulopathy based on laboratory values. When controlling baseline MAP, dilution with LR increased bleeding, confirming a functional coagulopathic state.     

BISAP联合凝血指标对急性胰腺炎严重程度评估的意义

目的:研究BISAP(bedside index for severity in AP)评分联合凝血指标对急性胰腺炎(acute pancreatitis,AP)严重程度评估的意义.方法:回顾2008-2012年中国医科大学附属盛京医院收治的166例AP患者的临床资料.对所有患者进行入院24h的BISAP、APACHE-Ⅱ评分,48h的Ranson’s及发病72h内CTSI评分,入院24h内抽取静脉血测定部分凝血活酶活化时间、凝血酶原时间、D-二聚体(D-dimer)、纤维蛋白原及血小板水平.分析凝血指标及BISAP评分对AP严重程度判断的意义,并通过ROC曲线分析二者联合对AP严重程度评估的意义.结果:多因素Logistic回归分析发现,D-dimer对AP严重程度评估具有独立预测意义;随着BISAP评分增加,SAP的比率增加;BISAP评分系统评估AP严重程度以2为临界点时Youden指数最大(0.541),ROC曲线下面积为0.836(0.776-0.896),并不逊于传统评分系统;BISAP评分系统联合D-dimer能更好地评估AP患者的严重程度.结论:BISAP是临床判断AP轻重程度的简单有效的指标,将BISAP与D-dimer联合应用使得对AP严重程度的评估更为准确.     

参附注射液治疗外伤性蛛网膜下腔出血后凝血相关因子的变化及其临床意义

目的 探讨参附注射液治疗外伤性蛛网膜下腔出血后患者血液中凝血相关因子的变化规律及其意义. 方法 选取本院收治的外伤性蛛网膜下腔出血患者65例,随机分为治疗组33例与对照组32例,对照组给予常规治疗,治疗组在对照组的基础上加用参附注射液静脉滴注,每日2次,连续用药14天.动态监测患者部分凝血活酶时间(APTT)、凝血酶原时间(PT)、D-二聚体并进行统计学处理. 结果 参附注射液治疗外伤性蛛网膜下腔出血患者的部分凝血活酶时间延长(APTT)、凝血酶原时间(PT)延长、D-二聚体下降. 结论 外伤性蛛网膜下腔出血早期应用参附注射液治疗,可以有效预防外伤性蛛网膜下腔出血患者的血管痉挛,预防颅脑损伤后微血栓的形成,降低脑梗塞风险,改善患者的预后.