不同抗凝强度的华法林对非瓣膜性心房纤颤抗栓的疗效

目的:探讨阿司匹林和不同抗凝强度华法林对预防非瓣膜性心房纤颤患者血栓栓塞发生的疗效和安全性.方法:选择172例非瓣膜性心房纤颤患者,随机分为阿司匹林组48例、低强度华法林抗凝组38例[国际标准化比值(INR)1.6～2.0]和中强度华法林抗凝组42例(INR 2.1～2.5)、高强度华法林抗凝组44例(INR 2.6～3.5),应用华法林抗凝并行INR监测,常规门诊随访2年,分析血栓栓塞和出血事件发生与INR的关系.结果:治疗后低、中、高强度华法林3组血栓栓塞发生率相当(P>0.05),华法林3组血栓栓塞发生率低于阿司匹林组(P<0.05),高强度华法林组出血发生率高于其他3组(P<0.05),低、中强度华法林组出血发生率与阿司匹林组大致相仿(P>0.05).结论:对非瓣膜性心房纤颤患者华法林(INR 1.6～2.5)抗栓治疗的疗效优于阿司匹林,出血发生率低,安全性好.     

停服华法林对风湿性心脏瓣膜病伴心房颤动患者血浆纤维蛋白原和血栓栓塞的影响

目的 探讨持续口服、停止口服及未服华法林抗凝治疗对风湿性心脏瓣膜病伴房颤患者血浆纤维蛋白原(Fg)含量和血栓栓塞发生率的影响.方法 将确诊风湿性心脏瓣膜病伴心房颤动患者92例,根据华法林口服情况分为三组:持续口服华法林组、停止口服华法林组及未服华法林组.分别测定外周静脉血浆纤维蛋白原(Fg)含量及观察各组血栓栓塞发生率.结果 停止口服华法林组血浆Fg含量为(413±142)mg/dl,显著高于持续口服华法林组(286±48)mg/dl,P＜0.01及未服华法林组(388±124)mg/dl,P＜0.05;持续口服华法林组与未服华法林组血浆Fg含量差异有统计学意义,P＜0.01.停止口服华法林组血栓栓塞发生率为(19.0%)明显高于持续口服华法林组(3.3%)和未服华法林组(7.3%),P＜0.01;持续口服华法林组与未服华法林组比较差异有统计学意义,P＜0.05.结论 风湿性心脏瓣膜病伴心房颤动患者停止口服华法林治疗后血浆纤维蛋白原(Fg)含量升高,致血栓栓塞危险明显超过未服华法林及持续口服华法林患者.     

服用华法林心房颤动患者体内维生素K1浓度和凝血酶原时间-国际标准化比值的临床分析

目的研究对比服用华法林患者体内维生素K1浓度和凝血酶原时间-国际标准化比值(PT-INR)的关系。方法回顾分析首次服用华法林心房颤动患者50例纳入治疗组,其中女性25例,男性25例;年龄43~74岁,平均年龄(54.62±10.92)岁,选择10例健康人作为对照组。利用高效液相(HPLC)及生化分析分别监测服药后第2、4、7天体内维生素K1浓度及PT-INR指标和血浆黏度。结果治疗组随着用药时间增加,体内维生素K1的浓度逐渐下降,而PT-INR值均逐渐升高,其中第4、7天与对照组和治疗组第2天比均有统计学差异(P均<0.05)。相关性分析采用Pearson检验得出PT-INR值与红细胞聚集指数及血浆黏度均为负相关(r=-0.702;r=-0.728),而维生素K1与红细胞聚集指数及血浆黏度则均为正相关(r=0.683;r=0.613)。结论服用华法林心房颤动患者体内维生素K1浓度与PT-INR呈负相关,维生素K1浓度与PT-INR一样能够反映心房颤动患者服用华法林的抗凝效果。     

长期口服华法林治疗的心房颤动患者起搏器植入围手术期不同抗凝方式的比较

目的探讨长期使用华法林治疗的心房颤动患者起搏器植入围手术期恰当的抗凝方式。方法回顾性分析2013年7月至2017年7月在我院心内科住院的需要接受起搏器植入治疗且长期服用华法林的房颤患者110例,根据围手术期抗凝方式的不同分为停用组33例、桥接组37例和继续组40例,分析不同抗凝方式与出血和栓塞事件发生率的关系。结果桥接组出血并发症发生率高于其他两组(P0.05),主要表现为囊袋血肿发生率明显升高(P0.05)。三组均未出现栓塞事件。结论对于需要植入起搏器的口服华法林的心房颤动患者,术前继续华法林抗凝治疗不会增加起搏器植入围术期出血事件的发生率,而肝素桥接抗凝则明显增加出血并发症。     

198例心脏机械瓣膜置换术患者口服华法林的临床监测及护理

目的研究心脏机械瓣膜置换术后口服华法林患者血浆凝血酶原前体蛋白(prothrombin precursor protein,PIVKA-Ⅱ)、凝血酶原时间(prothrombintime,PT)、国际标准化比率(international normalized rate,INR)的变化及其临床意义。方法 198例心脏机械瓣膜置换术后口服华法林患者为病例组,30例门诊体检人员为健康对照组,分别进行血浆PIVKA-Ⅱ、PT、INR测定。结果研究组首次服华法林后8h后,血浆PIVKA-Ⅱ浓度即显著增高,差异有统计学意义(P0.05);首次服华法林24h后,PT、INR显著增高,差异有统计学意义(P0.05)。抗凝后多数患者有不同程度的出血,其中2例出现腰大肌血肿,3例出现脑出血,1例出现脑血栓,经手术治疗、药物调整及护理后均康复。结论上述指标能较客观地反映心脏机械瓣膜置换术后口服华法林患者的病理变化过程。对患者进行心理治疗等护理可以提高治疗效果、减少并发症。     

达比加群酯或华法林治疗高龄非瓣膜性心房颤动合并射血分数下降性心力衰竭患者栓塞事件及出血事件发生率对比研究

目的选取2016年9月至2018年8月于渭南市第二医院内二科就诊的79例高龄非瓣膜性心房颤动(AF)合并射血分数下降性心力衰竭患者,在使用达比加群酯或华法林治疗后栓塞事件及出血事件发生率的对比研究。方法将79例患者随机分为两组,研究组39例予达比加群酯治疗,对照组40例使用华法林治疗,比较两组应用抗凝药物后的栓塞或血栓形成、凝血指标及出血事件的发生率。结果两组凝血酶原时间(PT)、凝血酶时间(TT)、纤维蛋白原(FIB)比较,差异无统计学意义(P0.05);两组国际标准化比值(INR)、活化部分凝血活酶时间(APTT)比较,差异有统计学意义(P0.05)。两组均未出现大出血、出血性脑卒中以及死亡相关病例。两组出现轻微出血现象的患者数量比较,差异有统计学意义,研究组显著低于对照组(P0.05),两组患者其余指标比较,差异均无统计学意义(P0.05)。结论达比加群酯胶囊治疗高龄非瓣膜性AF合并射血分数下降性心力衰竭患者的抗凝有效性与华法林相似,但其出血风险低于华法林。     

利伐沙班在起搏器围手术期应用的安全性分析

目的 观察口服利伐沙班抗凝患者起搏器围手术期囊袋出血的发生率,为优化起搏器围手术期抗凝治 疗提供证据。方法 回顾分析抗凝患者行起搏器植入术的临床资料,根据不同抗凝治疗方案将患者分为两组。A 组 (n =80)为长期口服华法林的患者,术前调整国际标准化比值(INR)至1.5~2.0,围手术期不停用华法林;B组(n = 72)患者围手术期持续口服利伐沙班。比较两组起搏器术后囊袋出血的发生率。结果 152例需抗凝治疗患者行起 搏器手术。A 组术后发生轻度囊袋出血4例,中度囊袋出血2例,重度囊袋出血1例。B 组患者72例,术后发生轻度 囊袋出血4例,中度囊袋出血1例。两组患者囊袋出血差异无统计学意义(P >0.05)。结论 围手术期持续应用利 伐沙班与华法林相比并不增加出血风险。     

华法林在心脏瓣膜病并心房颤动患者中的抗凝效果

目的探讨华法林在心脏瓣膜病并心房颤动(房颤)患者中的抗凝效果。方法对2017年3月-2019年12月期间我院收治的50例心脏瓣膜病并房颤患者使用华法林抗凝的情况进行回顾性研究,分成试验组(n=25)与对照组(n=25),对照组采取常规华法林给药方式和剂量进行治疗,试验组在采用华法林进行治疗前先进行"华法林个体化用药基因检测",观察两组治疗前后凝血指标、INR达标时间以及出血和血栓事件发生情况。结果两组在治疗前的PT值以及APTT值差异无统计学意义(P0.05),治疗后,试验组PT值以及APTT值均高于对照组(P 0.05);试验组INR达标时间较短(P 0.05);两组出血以及缺血事件发生情况差异无统计学意义(P0.05)。结论在对心脏瓣膜病并房颤患者使用华法林治疗前先进行"华法林个体化用药基因检测",抗凝效果显著,并可有效缩短INR达标时间。     

华法林抗凝患者起搏器术后预防囊袋出血的观察与护理

目的：评价不同护理方法预防华法林抗凝患者起搏器术后囊袋出血的疗效。方法回顾分析华法林抗凝患者行起搏器植入术的临床资料,根据术后采用不同预防囊袋出血措施分为两组。 A组患者术前调整INR至1.5～2.0,围手术期不停用华法林,术中应用凝血酶,术后延长弹力绷带加压包扎时间至48 h;B组患者术前调整INR至1.5～2.0,术前3 d停用华法林,改用低分子肝素替代抗凝治疗,术后恢复使用华法林,术后给予弹力绷带加压包扎24 h。比较两种方法预防起搏器术后囊袋出血的效果。结果共840例行起搏器手术患者中,有78例为长期使用华法林抗凝的患者。 A组患者42例,术后发生轻度囊袋出血4例,中度囊袋出血1例。 B组患者36例,术后发生轻度囊袋出血7例,中度囊袋出血3例,重度囊袋出血1例。结论华法林抗凝患者起搏器植入术后囊袋出血的风险增高,术中应用凝血酶,而术后延长弹力绷带加压时间对预防囊袋出血具有更好的疗效。     

品管圈活动对提高心脏瓣膜置换术后患者口服华法林抗凝治疗的知晓率及依从性的影响

目的探讨品管圈活动对提高心脏瓣膜置换术后患者口服华法林抗凝治疗的知晓率及依从性的影响。方法选取2016年1月～2018年12月本院收治的心脏瓣膜置换术后行华法林抗凝治疗的瓣膜性心脏病(VHD)患者98例,按随机数字表法分为研究组和对照组各49例。对照组给予常规护理干预,研究组给予品管圈活动管理,对比两组相关知识知晓率、治疗依从性、并发症及生活质量。结果研究组对口服华法林抗凝治疗相关知识知晓率显著高于对照组(P0.05);研究组华法林抗凝治疗依从率(91.84%)显著高于对照组(65.31%)(P0.05);研究组并发症发生率(6.12%)显著低于对照组(30.60%)(P0.05);入院时,两组GQOLI(生理功能、躯体功能、社会功能)评分比较无显著差异(P0.05);出院后,两组GQOLI评分较入院时比较显著上升,研究组GQOLI评分显著高于对照组(P0.05)。结论开展QCC活动可提高心脏瓣膜置换术后华法林抗凝治疗患者相关知识知晓率和治疗依从性,降低并发症发生,提高患者生活质量。     

Warfarin monitoring with viscoelastic haemostatic assays,thrombin generation,coagulation factors and correlations to Owren and Quick prothrombin time

The anticoagulant warfarin is commonly monitored with prothrombin time (PT). Viscoelastic haemostatic assays (VHA) are primarily used in situations of acute bleeding to guide haemostatic therapy. Much research has focused on VHA monitoring of new oral anticoagulants. However, many patients are still anticoagulated with warfarin and effect of warfarin anticoagulation on VHA is uncertain. The aim of this study was to assess warfarin anticoagulation on three different VHA and compare these findings with prothrombin time (PT), coagulation factor analyses and a thrombin generation assay (TGA). Citrated whole blood was drawn from 80 patients admitted for routine PT-INR Owren. VHA analysis with ROTEM (EXTEM, INTEM and FIBTEM), ReoRox (Fibscreen 1 and 2) and Sonoclot (gbACT+) was performed. Blood was also drawn for plasma analysis with PT (PT-INR Owren and PT Quick), TGA and analysis of factors I, II, VII, IX and X. Extrinsically activated VHA, including ROTEM EXTEM and FIBTEM Clotting Time (CT) and ReoRox Fibscreen1 and 2 clot onset time 1 correlated moderately with PT-INR Owren , with R 0.66–0.71. These four variables were likely to be prolonged above reference interval in patients with prolonged PT-INR Owren >1.2. Two patients with normal ROTEM CTs had Owren PT-INRs >1.5. Warfarin affects extrinsically activated VHA variables of initial clotting. The role of VHA for clinical decision-making in patients planned for invasive procedures, such as spinal/epidural anaesthesia needs further study. None of the recent guidelines on regional anaesthesia include VHA testing to define adequate haemostasis.     

华法林治疗急性下肢深静脉血栓形成患者凝血酶原-国际标准化比值国人适宜性有效值的初步探讨

目的 初步探讨华法林治疗急性期下肢深静脉血栓形成(DVT)患者适宜国人的凝血酶原-国际标准化比值(PT-INR).方法 选择具有华法林抗凝治疗适应证的DVT患者87例,随机分为A、B 2组,A组(47例)应用华法林,调整PT-INR在1.7～2.5,B组(40例)应用华法林,调整PT-INR在2.0～3.0,比较华法林治疗的有效性及出血并发症的发生率.结果 A组47例患者,46例肢体肿胀明显减退消失,1例无效,经彩超、GT及肿瘤标志物检查,考虑为盆腔肿瘤,有效率为98%;全部患者无明显出血症状.B组40例患者,38例肢体肿胀明显减退消失,2例症状好转不明显,其中Cockett综合征1例,另一例原因不明,有效率为95%;3例出现轻度牙龈及鼻黏膜出血,1例出现胃肠道内出血.2组无肺栓塞发生.结论 国人急性DVT治疗中PT-INR调整在1.7～2.5同样有效,且出血等并发症明显减少.

Abstract：

Objective To explore the suitable range of PT-INR for Chinese people with acute deep venous thrombosis (DVT) treated by warfarin anticoagulation therapy. Methods Eighty seven DVT patients with indications to warfarin anticoagulation therapy were enrolled into the study and divide into two groups randomly. Patients from group A (n=47) took warfarin to adjust the PT-INR to range 1.7-2. 5,and patients from group B (n =40) took warfarin to adjust the PT-INR to range 2. 0-3. 0. The therapeutic effectiveness and the incidence of bleeding complications were compared between two groups. Results Forty-six patients (46/47,98%) had limb swelling symptoms relief in group A with one exception,which was diagnosed as pelvic tumor by ultrasonography,CT and tumor markers examination later. No patient underwent bleeding in group A Thirty eight patients (38/40,93%) had limb swelling symptoms relief in group group B with two exceptions,of which one case had Cockett syndrome and the other one had unknown aetiology. The total effective rate of group B was 95% . As to the complications of this group,3 patients had slight gum and nasal mucous membrane bleeding, 1 patient developed gastrointestinal bleeding. No patients had pulmonary embolism in both groups. Conclusion For Chinese people,anticoagulation therapy of acute deep venous thrombosis to adjust the range of PT-INR to 1.7-2. 5, shows good effectiveness and significantly reduced bleeding complications.     

凝血酶生成试验在遗传性凝血因子缺陷症患者出血评估中的价值

目的 探讨遗传性凝血因子V(FV)、X(FX)和XI(FXI)缺陷及FV和凝血因子VⅢ(FVⅢ)联合缺陷(F5F8D)患者的血浆凝血因子活性、凝血酶生成曲线各参数和临床出血症状之间的关系.方法 采集遗传性FV(n=24)、FX(n=14)和FXI(n=18)缺陷及F5F8D(n=8)患者及携带者的外周血进行常规出凝血检...     

Anticoagulation monitoring part 1: warfarin and parenteral direct thrombin inhibitors

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in the management of warfarin and parenteral direct thrombin inhibitors. DATA SOURCES: Scientific articles were identified through a MEDLINE search (1966-August 2004), manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The prothrombin time expressed as the international normalized ratio (PT-INR) is a well-established test for monitoring warfarin anticoagulation. Multiple devices are available for POC testing. Because there is no universally accepted standard, the performance of each device is typically tested against a standard test performed in a reference laboratory. Performance of currently available devices, as measured by correlations to a standard reference laboratory PT-INR, may be considered very good and acceptable for use in patient care. Utilization of patient self-testing and patient self-monitoring of warfarin anticoagulation using POC devices is increasing. Parenteral direct thrombin inhibitors are typically monitored using a standard laboratory activated partial thromboplastin time. Some research has shown that POC monitoring of direct thrombin inhibitors using the ecarin clotting time is helpful for patients undergoing cardiopulmonary bypass surgery, although that test is not readily available. CONCLUSIONS: POC testing for anticoagulation therapy has been available for >20 years. Multiple POC devices are available to monitor warfarin. There is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC monitoring of warfarin via the PT-INR is an integral part of clinical practice. Additional research evaluating POC monitoring of direct thrombin inhibitors is necessary.     

TRANSFUSION PRACTICE: Thrombin generation in trauma patients

BACKGROUND: Trauma patients are at risk of developing an acute coagulopathy of trauma (ACT) related to tissue injury, shock, and hemodilution. ACT is incompletely understood, but is similar to disseminated intravascular coagulation (DIC) and is associated with poor outcome. STUDY DESIGN AND METHODS: Thrombin generation assays were used to evaluate plasma hemostasis in 42 trauma patients, 25 normal subjects, and 45 patients on warfarin and in laboratory‐prepared factor reduced plasma. RESULTS: Prolonged prothrombin time (PT), more than 18 seconds, or an international normalized ratio of greater than 1.5 was present in 15 trauma patients indicating possible ACT. Native thrombin generation (no activator added, contact activation blocked) showed that Trauma with ACT patients had lag times 68% shorter and peak thrombin generation threefold higher than normal patients indicating the presence of circulating procoagulants capable of initiating coagulation systemically. Trauma patients had lower platelet counts and fibrinogen and Factor (F)II levels putting them at increased risk of bleeding. In laboratory‐prepared isolated factor‐reduced samples and in patients with vitamin K–dependent factor deficiency due to warfarin, thrombin generation decreased in direct proportion to FII levels. In contrast, in diluted plasma and in trauma patients with reduced factor levels, thrombin generation was increased and associated with slower inhibition of thrombin generation (prolonged termination time) and decreased antithrombin levels (43% of normal in Trauma with ACT). CONCLUSIONS: Thrombin generation studies indicate that Trauma with ACT patients show dysregulated hemostasis characterized by excessive non–wound‐related thrombin generation due to a combination of circulating procoagulants capable of activating coagulation systemically and reduced inhibitor levels allowing systemic thrombin generation to continue once started.     

Activated protein C resistance determined with a thrombin generation-based test is associated with thrombotic events in patients with lupus anticoagulants

BACKGROUND: Several studies suggest that antiphospholipid antibodies interfere with the activity of activated protein C (APC). This acquired form of APC resistance has been proposed as a possible pathogenic mechanism underlying hypercoagulability associated with the antiphospholipid syndrome (APS). OBJECTIVES: We wanted to investigate the inhibitory effect of recombinant APC (rAPC) on ex vivo thrombin generation in plasma and the modification of this effect by the presence of lupus anticoagulants (LA). PATIENTS/METHODS: We analyzed plasmas from 81 patients with LA (52 patients fulfilling the criteria for the APS) and 91 controls. Percent inhibition of the endogenous thrombin potential (ETP) as a parameter of APC sensitivity was determined in plasmas using a thrombin generation-based APC resistance test probed with rAPC. All results were normalized using pooled normal plasma (PNP) as a reference. RESULTS: Normalized percent inhibition of ETP by APC was lower in patients with LA [61.4%, 95% confidence interval (CI) 45.8-74.5%] compared to controls (107.8%, 95% CI: 107.1-109.3%). In patients with LA and APS, median inhibition was lower than in patients with LA without APS (44.6%, 95% CI: 30.1-55.7% vs. 78.8%, 95% CI: 73.9-95.8%). This difference also persisted when patients on warfarin therapy were excluded from the APS subgroup. CONCLUSIONS: APC resistance can be demonstrated with a thrombin generation-based test in a majority of patients with the LA laboratory phenotype. A history of thrombotic events in patients with LA is associated with a stronger resistance to the anticoagulant effect of APC.     

Optimizing warfarin reversal – an ex vivo study

Summary.  Background: Warfarin reversal is a common clinical situation. This is commonly performed using vitamin K and, depending on the urgency, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), or activated factor VII. Even though PCCs are widely used, the ideal dosing regimen is far from established. Objectives: To verify differences in warfarin reversal patterns using FFP, recombinant FVIIa (rFVIIa), and PCC; and to test the hypothesis that supratherapeutic International Normalized Ratios (INRs) might not correlate with thrombin generation (TG) and identify the ideal concentrations of PCC required to reverse various INR thresholds. Methods: We studied the effects of FFP, rFVIIa and Beriplex  P/N on the INR and TG, using the calibrated automated thrombography assay in ex vivo warfarinized plasma. Plasmas with different INRs were spiked with different concentrations of Beriplex  P/N. Results: Beriplex  P/N was the only agent that completely normalized TG and the INR. The endogenous thrombin potential (ETP) and the peak thrombin showed a significant negative correlation with all INRs. The ETP and velocity of TG reached a plateau at an INR of ∼ 4.0. A concentration equivalent to a dose of 30 IU kg⁻¹ Beriplex  P/N normalized the ETP, the INR, FII, FVII, FIX and FX of samples with INRs  ≥ 4.0. Higher doses resulted in hypercoagulable TG patterns. A concentration equivalent to a dose of 20 IU kg⁻¹ was sufficient to reverse warfarin at an INR range of 2.0–3.9, as judged by the same tests. Conclusions: Warfarin reversal algorithms could be simplified with the adoption of this strategy utilizing two doses of PCC, depending on the INR of the patient. This would also lead to cost reductions and, possibly, a reduction in thrombotic risk.     

Coagulation factors and the protein C system as determinants of thrombin generation in a normal population.

BACKGROUND: Thrombin generation is a powerful tool to probe overall plasma coagulability. OBJECTIVE: To determine which plasma factors influence the various parameters of the thrombin generation curve, for example lag time, peak height and endogenous thrombin potential (ETP), under different experimental conditions. PATIENTS AND METHODS: Plasma levels of coagulation factors and inhibitors, as well as thrombin generation at 1 pm tissue factor (TF) +/- thrombomodulin (TM) and at 13.6 pm TF +/- activated protein C (APC), were determined in plasma from 140 healthy individuals. Data were analysed by multiple regression models. RESULTS: Thrombin generation increased with age and was higher in females than in males. Under all conditions, the lag time was mainly dependent on the levels of free tissue factor pathway inhibitor (TFPI), free protein S (PS), factor VII (FVII), FIX and fibrinogen. The major determinants of thrombin generation (ETP and peak height) at 1 pm TF were fibrinogen, FXII (despite inhibition of contact activation), free TFPI and antithrombin (AT), both in the absence and in the presence of TM. Thrombin generation in the presence of TM was also dependent on protein C levels. At 13.6 pm TF, thrombin generation was determined by prothrombin, AT, fibrinogen, free TFPI and FV levels in the absence of APC, and by free TFPI, free PS and FX levels in the presence of APC. CONCLUSIONS: The lag time, ETP and peak height of thrombin generation depend on the levels of multiple coagulation factors and inhibitors. The specific assay determinants vary with the experimental conditions.     

凝血酶生成试验在血友病患者中的应用

目的：探讨凝血酶生成试验在血友病患者中的应用。方法：收集134例血友病患者[其中血友病A（HA）114例，血友病B（HB）20例1的临床资料，根据FⅧ：C／FIX：C不同，将无FⅧ／FⅨ抑制物的132例HA／HB患者分成重型（FⅧ：C／FIX：C〈1％）、中型（FVIU：C／FIX：C1％～5％）及轻型（FⅧ：C／FIX：C6％～25％）3组，检测凝血酶生成、FⅧ：C／FIX：C及其抑制物。结果：重型HA／HB患者与轻型者比较，出血频度及凝血酶生成各指标差异均有统计学意义（P〈0．01）；而重型者与中型者比较，除延迟时间和达峰时间差异有统计学意义外（P〈0．01），其余指标差异均无统计学意义；中型者与轻型者比较，除延迟时间和达峰时间差异无统计学意义外，其余指标差异均有统计学意义（P〈0．01）。HA／HB患者的出血频度与FⅧ：C或FIX：C无关（P=0．16），而与凝血酶生成潜力（ETP）密切相关（P=0．0001）：结论：凝血酶生成试验可作为预测HA／HB患者出血风险的有效手段。     

The impact of vitamin K-dependent factor depletion by warfarin on platelet-rich thrombosis after deep arterial injury.

Although the central role of thrombin in arterial thrombosis is well established, the efficacy of vitamin K-dependent factor depletion by warfarin at preventing this process has not been established. To assess the efficacy of warfarin in the prevention of arterial thrombosis, two intensities of anticoagulation were compared in a well-characterized porcine model of carotid angioplasty. For 10 days prior to angioplasty, pigs received either high-dose warfarin (n = 9), low-dose warfarin plus aspirin (n = 9), or control tablets (n = 10). Injured arteries were assessed for (111)In-platelet ( x 10(6) cm(-2)) and (125)I-fibrin(ogen) (molecules x 10(12) cm(-2)) deposition and the incidence of macroscopic thrombus. Platelet (30 +/- 7 vs. 332 +/- 137; P = 0.001) and fibrinogen (156 +/- 17 vs. 365 +/- 90; P < 0.05) deposition were significantly reduced in animals receiving high-intensity warfarin whereas low-intensity warfarin/ASA (520 +/- 240 and 1193 +/- 638) was similar to control (P =NS). At the time of angioplasty, the PT-INR and vitamin K-dependent factors varied over a broad range. The greatest reduction of platelet and fibrinogen deposition occurred as the PT-INR increased from 1.0 to 2.2. Increasing the PT-INR beyond 3.0 resulted in little, if any, incremental reduction of either platelet or fibrinogen deposition. Macroscopic thrombus was abolished at PT-INR > 2.2. Despite a broad range of vitamin K factor activities, no single factor was predictive of either platelet or fibrinogen deposition. Warfarin at PT-INR > 2.2 effectively eliminates thrombosis following deep arterial injury. Arterial thrombosis correlates poorly with any single vitamin K-dependent factor but rather appears to be a function of the entire extrinsic coagulation pathway as measured by the PT-INR.