Correlations between rotational thromboelastometry (ROTEM) and standard coagulation tests following viper snakebites

BackgroundA high prevalence of venom-induced consumption coagulopathy has been reported in individuals with viper snakebites. Rotational thromboelastometry (ROTEM) is a rapid technique that could be advantageous in assessing and monitoring coagulation disorders.PurposeTo explore correlations between ROTEM and standard coagulation tests.Patients and methodsThis prospective observational study was performed among 41 patients with viper envenomation admitted to the Vietnam Poison Control Center from April 2016 to October 2017. Standard coagulation measurements [platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level] and ROTEM indicators [clotting time (CT), amplitude (at set time: 5 and 10 minutes), clot information time (CFT) and maximum clot firmness (MCF) for extrinsic (EXTEM), intrinsic (INTEM), and fibrin based (FIBTEM) ROTEM] were obtained.ResultsFor INTEM, EXTEM, the FIBTEM, proportions of patients with prolonged CT were 34.1%, 63.4%, and 61.0% respectively and the proportions of patients with decreased MCF were 62.2%, 62.2%, and 35.5%, respectively. Moderate correlations were observed between PT and EXTEM CT (r = 0.627), aPTT and INTEM CT (r = 0.626), fibrinogen and FIBTEM MCF (r = 0.723), and platelet count and EXTEM MCF (0.60).ConclusionROTEM indicated a hypocoagulation state in patients with viper snakebite and was moderately correlated with standard coagulation parameters.     

A comparative evaluation of rotation thromboelastometry and standard coagulation tests in hemodilution-induced coagulation changes after cardiac surgery

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple perturbations in cellular and humoral elements of coagulation. A timely and comprehensive method to evaluate hemostasis would be helpful in the management of bleeding patients after CPB. The assessment of whole blood coagulation using rotation thromboelastometry (ROTEM) was compared to coagulation tests routinely performed during cardiac surgery. STUDY DESIGN AND METHODS: Blood was obtained from 26 patients undergoing CPB surgery at baseline, at 60 minutes on CPB, at the end of CPB, and on admission to intensive care unit. ROTEM tests (extrinsically activated [EXTEM], intrinsically activated [INTEM], specific clot formation [FIBTEM]), prothrombin time, activated partial thromboplastin time, platelet (PLT) count, fibrinogen, prothrombin level, antithrombin level, and thrombin generation (TG) measurement were performed. RESULTS: We observed strong correlations between FIBTEM‐amplitude at 10 minutes (A10) and fibrinogen level (r = 0.87; p < 0.001) and between EXTEM/ INTEM‐A10 variables and PLT count (r = 0.72 and 0.67, respectively; p < 0.001). Receiver operating characteristic analysis demonstrated that EXTEM‐A10 and INTEM‐A10 are predictive of thrombocytopenia below 80 × 10⁹/L (area under the curve [AUC], 0.83 and 0.82, respectively), and FIBTEM‐A10 was highly predictive of fibrinogen level below 200 mg/dL (AUC, 0.96). There were only weak correlations found between TG peak and clot formation time of EXTEM or INTEM (r = 0.30 and 0.29, respectively; p < 0.05). CONCLUSION: ROTEM variables demonstrated clinically relevant correlations with PLT counts and fibrinogen levels. In particular, decreasing levels of fibrinogen can be quickly determined (<15‐20 min) using FIBTEM.     

Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study

IntroductionThe purpose of this study was to re-evaluate the findings of a smaller cohort study on the functional definition and characteristics of acute traumatic coagulopathy (ATC). We also aimed to identify the threshold values for the most accurate identification of ATC and prediction of massive transfusion (MT) using rotational thromboelastometry (ROTEM) assays.MethodsIn this prospective international multicentre cohort study, adult trauma patients who met the local criteria for full trauma team activation from four major trauma centres were included. Blood was collected on arrival to the emergency department and analyzed with laboratory international normalized ratio (INR), fibrinogen concentration and two ROTEM assays (EXTEM and FIBTEM). ATC was defined as laboratory INR >1.2. Transfusion requirements of ≥10 units of packed red blood cells within 24 hours were defined as MT. Performance of the tests were evaluated by receiver operating characteristic curves, and calculation of area under the curve (AUC). Optimal cutoff points were estimated based on Youden index.ResultsIn total, 808 patients were included in the study. Among the ROTEM parameters, the largest AUCs were found for the clot amplitude (CA) 5 value in both the EXTEM and FIBTEM assays. EXTEM CA5 threshold value of ≤37 mm had a detection rate of 66.3% for ATC. An EXTEM CA5 threshold value of ≤40 mm predicted MT in 72.7%. FIBTEM CA5 threshold value of ≤8 mm detected ATC in 67.5%, and a FIBTEM CA5 threshold value ≤9 mm predicted MT in 77.5%. Fibrinogen concentration ≤1.6 g/L detected ATC in 73.6% and a fibrinogen concentration ≤1.90 g/L predicted MT in 77.8%. Patients with either an EXTEM or FIBTEM CA5 below the optimum detection threshold for ATC received significantly more packed red blood cells and plasma.ConclusionsThis study confirms previous findings of ROTEM CA5 as a valid marker for ATC and predictor for MT. With optimum threshold for EXTEM CA5 ≤ 40 mm and FIBTEM CA5 ≤ 9 mm, sensitivity is 72.7% and 77.5% respectively. Future investigations should evaluate the role of repeated viscoelastic testing in guiding haemostatic resuscitation in trauma.     

Diagnosis of early coagulation abnormalities in trauma patients by rotation thrombelastography

BACKGROUND: Reagent-supported thromboelastometry with the rotation thrombelastography (e.g. ROTEM) is a whole blood assay that evaluates the visco-elastic properties during blood clot formation and clot lysis. A hemostatic monitor capable of rapid and accurate detection of clinical coagulopathy within the resuscitation room could improve management of bleeding after trauma. OBJECTIVES: The goals of this study were to establish whether ROTEM correlated with standard coagulation parameters to rapidly detect bleeding disorders and whether it can help to guide transfusion. METHODS: Ninety trauma patients were included in the study. At admission, standard coagulation assays were performed and ROTEM parameters such as clot formation time (CFT) and clot amplitude (CA) were obtained at 15 min (CA(15)) with two activated tests (INTEM, EXTEM) and at 10 min (CA(10)) with a test analyzing specifically the fibrin component of coagulation (FIBTEM). RESULTS: Trauma induced significant modifications of coagulation as assessed by standard assays and ROTEM. A significant correlation was found between prothrombin time (PT) and CA(15)-EXTEM (r = 0.66, P < 0.0001), between activated partial thromboplastin time and CFT-INTEM (r = 0.91, P < 0.0001), between fibrinogen level and CA(10)-FIBTEM (r = 0.85, P < 0.0001), and between platelet count and CA(15)-INTEM (r = 0.57, P < 0.0001). A cutoff value of CA(15)-EXTEM at 32 mm and CA(10)-FIBTEM at 5 mm presented a good sensitivity (87% and 91%) and specificity (100% and 85%) to detect a PT > 1.5 of control value and a fibrinogen less than 1 g L(-1), respectively. CONCLUSIONS: ROTEM is a point-of-care device that rapidly detects systemic changes of in vivo coagulation in trauma patients, and it might be a helpful device in guiding transfusion.     

Hyperfibrinolysis is common in out-of-hospital cardiac arrest : Results from a prospective observational thromboelastometry study

Background

Cardiocirculatory arrest (CCA) activates procoagulant pathways. It has also been reported to inhibit fibrinolysis, resulting in fibrin deposition and further impairment of blood flow. Until now, no studies have used whole-blood viscoelastic tests to characterize coagulation and the impact of fibrinolysis in out-of-hospital cardiac arrest (OHCA).

Methods

Patient with established OHCA who underwent cardiopulmonary resuscitation (CPR) were enrolled. Blood samples were obtained immediately after placement of an intravenous line at the scene, for full blood cell count, standard coagulation tests and rotational thromboelastometric (ROTEM^®) analyses. Patients with return of spontaneous circulation (ROSC) were compared to non-ROSC patients.

Results

Fifty-three patients (median age 67 years, interquartile range: 56–73 years) were included in the study. ROSC was established in 25 patients. Prothrombin time index (PTI) was significantly lower and activated partial thromboplastin time (aPTT) was significantly prolonged in non-ROSC patients compared to ROSC patients. Clotting time (CT) in the extrinsically activated ROTEM test (EXTEM) was significantly longer in non-ROSC versus ROSC patients. For the remaining EXTEM parameters, there were no significant differences between ROSC and non-ROSC patients. Hyperfibrinolysis (maximum lysis > 15% according to ROTEM test results) was observed in 19 patients (35.8%). There was no difference between ROSC and non-ROSC patients in the incidence of hyperfibrinolysis.

Conclusions

PTI, aPTT and EXTEM CT revealed significant differences between ROSC and non-ROSC patients. Hyperfibrinolysis according to ROTEM test results was much more common than previously assumed. Routine use of fibrinolytic therapy in all patients with prolonged CPR cannot therefore be recommended.     

Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery

Introduction

Thromboembolic complications contribute substantially to perioperative morbidity and mortality. Routine laboratory tests do not detect patients with acquired or congenital hypercoagulability who may be at increased risk of perioperative thromboembolism. Rotational thromboelastometry (ROTEM) is a digitized modification of conventional thromboelastography that is stable and technically easy to use. We designed a prospective observational study to evaluate whether preoperative ROTEM can identify patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery.

Methods

Preoperative ROTEM analysis using extrinsic rotational thromboelastometry (EXTEM), intrinsic rotational thromboelastometry (INTEM), and fibrinogen rotational thromboelastometry (FIBTEM) activators was performed on 313 patients undergoing major non-cardiac surgery. Patients’ medical records were reviewed after discharge for results of standard coagulation studies - partial thromboplastin time (PTT), international normalized ratio (INR), platelet count - and evidence of thromboembolic complications during their hospital stay. A thromboembolic complication was defined as a new arterial or deep venous thrombosis, catheter thrombosis, or pulmonary embolism diagnosed by ultrasound or spiral chest computed tomography.

Results

Ten patients developed postoperative thromboembolic complications, of whom 9 had received standard prophylaxis with subcutaneous enoxaparin or heparin. There was no indication of by PTT, INR, or platelet count. Preoperative EXTEM and INTEM activators that assess fibrin clot formation and platelet interaction indicated that these patients had significantly lower clot formation time (CFT) and significantly higher alpha angle (α) and maximum clot firmness (MCF), compared to patients without thromboembolic complications. There was no significant difference for any parameter using FIBTEM activator, which excludes platelet interaction. Receiver operating characteristic (ROC) curves were constructed for these variables. INTEM clot firmness at 10 min (A10) was the best predictor of thromboembolic complications, with an ROC area under the curve of 0.751.

Conclusions

Our results indicate that preoperative ROTEM assays that include fibrin clot and platelet interaction may detect patients at increased risk for postoperative thromboembolic complications after major non-cardiac surgery. Future studies need to evaluate the clinical utility and cost effectiveness of preoperative ROTEM and better define the association between ROTEM values and specific hypercoagulable conditions.     

应用凝血酶生成试验评估肝硬化患者血栓形成风险的研究

目的：研究抗凝血因子和促凝血因子对凝血酶原时间（PT ）、活化部分凝血活酶时间（APTT ）和凝血酶生成试验（TGA）结果的影响,探讨TGA用于评估肝硬化患者血栓形成风险的价值。方法收集93名肝硬化患者和50名健康人群的血液标本,分别进行凝血象、凝血活酶、抗凝因子和抗凝血酶的测定。TGA利用荧光读数仪测定,通过软件监测绘制样本的凝血酶生成曲线。结果 PT受凝血因子（F）Ⅱ、FⅤ、FⅦ、FⅨ和蛋白C浓度的影响,而 APTT 结果主要由 FⅡ、FⅨ和 FⅩ决定。在5 pmol/L组织因子（TF）的TGA反应体系中,凝血酶生成潜力（ETP）比值受FⅡ、抗凝血酶和蛋白C水平的影响,并且肝硬化组与对照组之间没有明显差异;而在1 pmol/L T F反应体系中ET P比值主要由FⅨ和蛋白C决定,肝硬化组与对照组的ET P比值差异有统计学意义（P＜0．05）。结论 PT和 TGA 受凝血和抗凝因子的调控,并且 TGA实验对于蛋白C浓度变化较为敏感;TGA能够在PT延长的情况下,提示肝硬化患者存在血栓形成的风险,TGA可作为临床评估肝硬化患者血液高凝状态的敏感指标。     

ROTEM in the setting of liver transplant surgery reduces frozen plasma transfusion

BackgroundINR is traditionally used as a marker of clinical coagulopathy, but is suboptimal in liver disease patients due to rebalanced hemostasis and its ineffectiveness to predict bleeding. Rotational thromboelastometry (ROTEM) testing evaluates whole blood hemostasis, which may provide more accurate assessments with the EXTEM CT parameter than INR. Thus, in end-stage liver disease (ESLD) patients, we hypothesized that elevated INRs are associated with normal EXTEM CT values.MethodsA retrospective study assessing adult (>18) patients with ESLD and elevated INRs undergoing liver transplantation, was performed to assess correlations between INR and EXTEM CT. This included patients post-ROTEM implementation where all had pre-operative ROTEM testing; and patients up to one year pre-ROTEM implementation to compare transfusion utilization. Data abstracted also included patient demographics, coagulation testing results, liver disease etiology, and MELD score.ResultsThe study included 138 patients in the post-ROTEM group and 59 patients in the pre-ROTEM group. Normal EXTEM CT was observed in 95.3 % and 93 % of patients with INR of 1.3–1.8 and up to 3 respectively. There was no correlation between INR of 1.3–1.8 and EXTEM CT (? = 0.239), and only moderate correlation was observed with higher INRs (? = 0.617 with INRs >1.8). ROTEM-guided transfusion in liver transplant surgeries was associated with reduced plasma transfusion (OR 0.27, 95 % CI 0.12?0.58, p = 0.001) after adjusting for red cell utilization and coagulation testing.ConclusionOur study suggests ROTEM may be advantageous for evaluating coagulopathy in patients with liver disease and ROTEM-guided transfusion reduces plasma transfusion.     

Role of thrombelastometry for the monitoring of factor XIII. A prospective observational study in neurosurgical patients

Recently published studies give evidence, that an increased maximum lysis in the APTEM? - test (ML60 > 12%) of the ROTEM? (Tem International GmbH, Munich, Germany) might indicate a factor XIII deficiency (FXIII < 70%). It was the aim of this study to investigate the feasibility of thrombelastometric measurements with the ROTEM device to reflect the isolated influence of FXIII on clot stability and therefore to indicate potential factor XIII deficiencies. Patients, method: After approval by the local Scientific and Ethic Review Board, 26 consecutive patients, scheduled for elective craniotomy for tumour resection, were prospectively enrolled into this study. Blood samples were taken for conventional laboratory coagulation analyses, FXIII analyses and thrombelastometric measurements (EXTEM, FIBTEM and APTEM tests) after induction of general anaesthesia (T1), before skin incision (T2) as well as at (T3) and 24 hours after (T4) postoperative admission to ICU, respectively. Statistical analyses included Spearman rank order correlations and multiple linear regressions. Results: FXIII concentrations did not correlate with the ML60 in the APTEM test at any measuring point. Neither platelet count nor fibrinogen nor FXIII concentrations were of predictive value for ML60 of the APTEM test. Conclusion: The results lead to the assumption that thrombelastometric measurements may not be appropriate for the perioperative monitoring of FXIII concentration.     

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.     

Plasma predilution with addition of depleted plasma in a prothrombin time reagent improves the agreement between different prothrombin time methods

Background. The Quick (plain thromboplastins) and Owren (combined thromboplastins, with the addition of bovine plasma with vitamin K‐dependent factors depleted) prothrombin time (PT) methods are used for measuring prothrombin time; for instance, in monitoring anticoagulation therapy with vitamin K antagonists. In most Quick PT methods, the final plasma dilution is 1/3 compared to Owren methods, which have a final dilution of 1/21. The Quick PT methods are associated with larger inter‐laboratory variations than the Owren PT methods. Objectives. We investigated whether dilution of the sample or thromboplastin has any impact on the correlation between the different PT methods. Material and methods. Plasma samples were analysed undiluted and prediluted in buffer, with adsorbed bovine plasma added, and by using rabbit brain or human placenta thromboplastins. Bootstrapping (re‐sampling) was utilized to estimate the difference in correlations between PT of different reagents at different dilutions of plasma. Results and conclusions. We found the best correlations for combined reagents when the sample was prediluted 7‐fold (r = 0.95) or more, and lowest when the sample was undiluted (r = 0.67). The source of thromboplastin had only a minor impact, if any, on the PT results. It was impossible to test whether predilution of plasma samples improved the correlation between Quick PT methods due to absence of clotting in many samples. We suggest that the Owren‐style sample predilution is preferable for the harmonization of PT results and to overcome the large inter‐laboratory variations that are associated with Quick PT methods to the benefit of patients on oral anticoagulation.     

FIBTEM provides early prediction of massive transfusion in trauma

Introduction

Prediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM^®) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT.

Methods

This retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM^® analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).

Results

Of 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).

Conclusions

FIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.     

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.     

The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients

Background

Hyperosmolar therapy, using either hypertonic saline (HTS) or mannitol (MT), is considered the treatment of choice for intracranial hypertension, a disorder characterized by high intracranial pressure (ICP). However, hyperosmolar agents have been postulated to impair coagulation and platelet function. The aim of this study was to identify whether HTS and MT could affect coagulation in moderate traumatic brain injury (TBI) patients.

Comparison of quick and owren prothrombin time with regard to the harmonisation of the International Normalised Ratio (INR) system.

Prothrombin time (PT) is tested mostly to monitor patients on oral anticoagulant treatment. The International Normalised Ratio (INR) was introduced to improve and harmonise PT results and therapeutic range globally for patient care and the scientific literature. We studied the Quick PT in 179 patients and the Owren PT in 137 patients on oral anticoagulant therapy using two different reagents for the two methods of measuring PT. We assessed the clinical significance of the INR results obtained by each method using the two reagents and compared the Quick and Owren methods. We conclude that with the Quick method individual INR results differed from each other too much clinically, while using the Owren method individual INR results were clinically acceptable. Our opinion is that we should develop the INR system using the Owren PT method rather than the Quick to improve patient care.     

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.     

凝血酶生成试验在监测华法林抗凝治疗中的应用

目的 探讨不同抗凝强度口服华法林治疗患者的凝血酶生成情况及其与出血的关系以及凝血酶生成试验在监测华法林抗凝治疗中的应用.方法 采集78例因心脏瓣膜置换术后房颤而口服华法林3个月以上的患者血样,检测凝血酶原时间-国际正常化比值(FT-INR)及凝血酶生成状况.结果 华法林治疗组按PT-INR不同分成三组:I组23例,PT-INR为1.51～2.00;Ⅱ组39例,PT-INR为2.01～3.00;Ⅲ组16例,PT-INR为3.01～4.26.三组凝血酶生成的延迟时间(lagtime)、峰值(peak)、达峰时间(ttpeak)都存在显著性差异(P《0.01),而反映凝血酶总体生成量的指标凝血酶生成潜力(endogenous thrombin potential,ETP),Ⅰ组和Ⅱ组比较差异存在统计学意义(P=0.0001),Ⅱ组和Ⅲ组比较差异无统计学意义(P=0.06).有出血并发症的患者5例,其ETP值小于正常对照组的15%.结论 口服华法林抗凝治疗患者,当PT-INR》3.0后,提高剂量会增加出血风险,但并不降低凝血酶生成量.服用华法林抗凝治疗期间同时检测PT-INR和ETP能更好地反映机体的凝血状态,从而有效地防止出血发生.     

Comparison of thromboelastometry by ROTEM® Delta and ROTEM® Sigma in women with postpartum haemorrhage

Haemostatic treatment in women experiencing postpartum haemorrhage is increasingly based on point-of-care devices such as ROTEM^® thromboelastometry. Recently, a fully automated successor of the ROTEM^® Delta device, the ROTEM^® Sigma was introduced. To determine whether these devices provide similar results, we compared ROTEM^® parameters using the ROTEM^® Delta and Sigma devices in women experiencing postpartum haemorrhage. Prospective observational cohort study of 23 women experiencing postpartum haemorrhage. ROTEM^® INTEM, EXTEM, FIBTEM and APTEM measurements handled by the ROTEM^® Delta and Sigma devices were compared. ROTEM^® FIBTEM values were also related to Clauss fibrinogen values. A correlation of Spearman’s r (r_s) varying between 0.76 and 0.95 was displayed between clot firmness measured in millimeters at 5 (A5), 10 (A10) and 20 (A20) minutes after start of clot formation measured by EXTEM, INTEM and APTEM assays executed on both devices; A5, A10 and A20 of FIBTEM correlated less well (r_S between 0.71 and 0.74), especially after five and ten minutes. Correlation between both devices regarding clotting time (CT) was poor. The observed correlation between levels of Clauss fibrinogen and FIBTEM A5 was r_s = 0.70, (95% confidence interval (CI): 0.38 to 0.87) for Delta and r_s = 0.85, (CI 0.65 to 0.94) for Sigma. A5, A10 and A20 measured in EXTEM, INTEM and APTEM obtained from ROTEM^® Delta and Sigma devices were similar. EXTEM, FIBTEM and APTEM CT values from both devices showed no correlation. Substantial variation was found between FIBTEM assays of the devices. Consequently, results of FIBTEM assays should always be interpreted in the context of device-specific reference values. Correlation with Clauss fibrinogen was better in the ROTEM^® Sigma device.     

Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities

BACKGROUND: Fresh-frozen plasma (FFP) is frequently transfused to patients with mild prolongation of coagulation values under the assumption that FFP will correct the coagulopathy. There is little evidence to support this practice, however. To determine the effect of FFP on coagulation variables and correlation with bleeding in patients with mildly prolonged coagulation values, a prospective audit of all FFP transfusions at the Massachusetts General Hospital between September 2, 2004, and September 30, 2005, was performed. STUDY DESIGN AND METHODS: All patients transfused with FFP for a pretransfusion prothrombin time (PT) between 13.1 and 17 seconds (international normalized ratio [INR], 1.1-1.85) and with a follow-up PT-INR within 8 hours of transfusion were included. Of 1091 units of FFP transfused, follow-up coagulation values within 8 hours were available for 121 patients (324 units). RESULTS: Transfusion of FFP resulted in normalization of PT-INR values in 0.8 percent of patients (95% confidence interval [CI], 0.0020-0.045) and decreased the PT-INR value halfway to normalization in 15.0 percent of patients (95% CI, 0.097-0.225). Median decrease in PT was 0.20 seconds (median decrease in INR, 0.07). Pretransfusion PT-INR, partial thromboplastin time, platelet count, and creatinine values had no correlation with red blood cell loss. CONCLUSION: It is concluded that transfusion of FFP for mild abnormalities of coagulation values results in partial normalization of PT in a minority of patients and fails to correct the PT in 99 percent of patients.     

Changes in the pharmacology of warfarin during long-term administration in dogs

Patients receiving an apparently appropriate maintenance dosage of oral anticoagulant may show unexpected changes in clotting status without readily identifiable cause. The object of this study was to determine whether a consistent change in the pharmacology of warfarin could account for the clinical observations during long-term dosing. Eleven healthy adult dogs received constant daily oral doses of warfarin for 4 weeks. Plasma warfarin concentration (W), measured by gas chromatography, and prothrombin time (PT), measured by the one-stage assay of Quick, were determined daily. W and PT decreased significantly (p less than 0.05) during the last 2 weeks of long-term treatment. No pharmacodynamic changes were observed after prolonged warfarin treatment, suggesting that the decreases in PT were due solely to the decreased W. The decrease in W was not due to an increased free warfarin fraction or to a reduction in W absorption from the gut. The reproducibility of these results was demonstrated in a second group of experiments done 1 month after the first set of studies. Over the entire group of dogs there was no consistent change in warfarin clearance during prolonged dosing. We conclude that during constant daily dosing, W and PT reach early peak values, after which they decrease to levels significantly below peak levels. These results suggest that clinical anticoagulation may require multiple dosage adjustments despite the early attainment of apparently therapeutic anticoagulant regulation with a fixed dosage schedule.