How do we transfuse blood components in cirrhotic patients undergoing gastrointestinal procedures?

The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence‐based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center.     

Hemostasis in Liver Disease: Implications of New Concepts for Perioperative Management

The hemostatic profile of patients with liver diseases is frequently profoundly different from that of healthy individuals. These complex alterations lead to abnormal results from routine laboratory tests, but because of the nature of these assays, they fail to accurately represent the patient’s hemostatic state. Nevertheless, based on abnormal laboratory coagulation values, it has long been assumed that patients with liver disease have a natural bleeding tendency and are protected from thrombosis. This assumption is false; the average patient with liver disease is actually in a state of “rebalanced hemostasis” that can relatively easily be tipped toward both bleeding and thrombosis. The new paradigm of rebalanced hemostasis has strong implications for the clinic, which are presented in this review. There is no evidence that prophylactic transfusion of plasma helps to prevent procedure-related bleeding. In addition, the presence of independent risk factors such as poor kidney status or infections should be carefully assessed before invasive procedures. Furthermore, central venous pressure plays an important role in the risk of bleeding in patients with liver diseases, so during procedures, a restrictive infusion policy should be applied. Finally, thrombosis prophylaxis should not be withheld from patients with cirrhosis or acute liver failure, and clinicians should be alert to the possibility of thrombosis occurring in these patients.     

肝硬化并发食管静脉曲张破裂出血风险、诱因分析和预见性护理

目的探讨肝硬化并发食管静脉曲张破裂出血（EVB）风险和诱因及其预见性护理方法。方法收集202例肝硬化门脉高压症住院病例的临床资料，对照分析影响出血的危险因素指标，统计导致出血的诱因，从而总结有关预见性护理方法。结果肝硬化病程、门静脉主干和脾静脉直径、食管静脉曲张程度和红色征是出血的高危因素，出血组有诱因可查的比例为62％（68／112），以饮食不当为最主要诱因。结论识别肝硬化并发EVB的危险因素和诱因，有利于针对高危患者采取预见性护理措施。     

Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery

The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient‐related and procedure‐related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non‐valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.     

Significant liver damage in patients with bleeding disorders and chronic hepatitis C: non-invasive assessment of liver fibrosis using transient elastography

Summary.  Background: Many patients with bleeding disorders have been infected with the hepatitis C virus (HCV), mainly with genotype 1. Antiviral treatment is only effective in 50% of these patients and is often accompanied by serious side effects. Consequently, careful selection of patients for treatment is warranted. Liver biopsies are generally not performed in these patients because of increased bleeding risk and high costs. We therefore assessed liver fibrosis and cirrhosis non-invasively using liver stiffness measurement (LSM). Methods: We enrolled 124 patients with bleeding disorders and chronic hepatitis C. Liver fibrosis was assessed by LSM using Fibroscan^®. In order to assess the validity of LSM in our hands, a separate group of 63 patients without bleeding disorders infected with HCV were evaluated with both LSM and biopsy. Results: In the validation study, liver elasticity was highly correlated with histological fibrosis stage (correlations coefficient 0.73, P  < 0.001). Based on LSM, 18% of patients with bleeding disorders and chronic hepatitis C had severe fibrosis, and 17% had cirrhosis after 34 years of infection (range 14–40). However, the prevalence of cirrhosis based on laboratory and ultrasonographic findings was only 7%. Independent risk factors for an increase in LSM were older age at infection, higher body mass index, presence of viral co-infection, and male gender. Fifteen out of 59 patients (25%) with an apparent indication for treatment (significant fibrosis by LSM) agreed to start antiviral therapy within 3 months. Conclusions: We found an unexpected high number of patients with significant fibrosis and cirrhosis in patients with bleeding disorders and hepatitis C detected by LSM, with considerable impact on the management of the disease.     

Future directions in utilization review: the role of transfusion algorithms

Transfusion practice guidelines and retrospective utilization review have been ineffective in curtailing the inappropriate use of blood and blood products, particularly in cardiac surgical patients. Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are at increased risk for excessive perioperative blood loss requiring transfusion of blood products. Recent evaluations have focused on the use of point-of-care coagulation assays for patient-specific therapy. Blood component administration in patients with excessive post-CPB bleeding is generally empiric, in part related to the times required to perform of laboratory-based tests. Methods are now available for rapid, on-site assessment of coagulation assays to allow appropriate, targeted therapy for acquired hemostatic abnormalities. Recent studies indicate that a rapid evaluation of thrombocytopenia and coagulation factor deficiencies, coupled with transfusion algorithms, can facilitate the optimal administration of transfusion-based therapy in patients who exhibit excessive bleeding after CPB. The use of point-of-care assays and transfusion algorithms may provide an effective concurrent method of utilization review of blood products in the surgical setting.     

无创性预测门脉高压静脉曲张出血的Logistic回归模型

目的 对肝硬化多普勒超声测定的腹腔血管血流参数及临床指标行优化组合，并建立Logistic回归模型，探讨该模型的应用价值。方法 肝硬化60例，其中出血3l例，无出血29例，联合行门静脉、脾静脉及肠系膜上静脉多普勒血管血流参数测定，采用单因素非条件Logistic回归分析，在此基础上行多因素Logistic回归，经优化组合后建立回归模型，并以该模型对14例患者随访1年。结果 出血危险性与门静脉血流量Qpv、脾静脉血流量Qspv、肠系膜上静脉血流量Qsmv及Qspv／Qpv正相关，与血小板平均体积(MPV)负相关。多因素Logistic回归分析，Qspv、Qsmv及MPV是与出血相关的独立影响因素。结合Qspv、Qsmv及MPV建立的回归模型对出血预测的灵敏度83．8％，特异性86．2％，阴性预测值85．7％，阳性预测值85．7％。结论 以超声多普勒联合检测脾静脉及肠系膜上静脉血流参数及MPV建立的Logistic回归模型在临床上无创性预测肝硬化门脉高压出血危险性是可行的。     

Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer

Purpose

Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting.

Methods

Through a retrospective chart review of all patients receiving integrative medicine consultations at the Integrative Therapies Program at Columbia University from January 1, 2007 to January 31, 2012, we describe the outcome of patients treated with YNB for management of uncontrolled bleeding.

Results

Four patients were identified who received topical YNB for uncontrolled bleeding; patients included two males and two females with diagnoses of solid tumors (n?=?3) and Burkitt’s lymphoma (n?=?1). Mean age was 15.5?years (range 15–17). Fifty percent had life-threatening bleeding from the tumor site and 50?% experienced uncontrollable epistaxis. All patients received preceding therapy with packed red blood cells and platelet transfusions, topical thrombin, and oral aminocaproic acid. Two patients used YNB in the inpatient setting, and all four patients used YNB as outpatients. In all patients, bleeding control improved with the addition of YNB to conventional hemostatic interventions. Two patients using YNB in their home reported control of bleeding episodes. There were no adverse events reported.

Conclusions

YNB may be an efficacious agent for uncontrolled bleeding in conjunction with conventional hemostatic agents in adolescents with advanced cancer. It is well accepted by patients. YNB may be especially valuable in the outpatient setting to prevent the recurrence of hemorrhage.     

Prevention of a first episode of variceal bleeding: role of duplex Doppler sonographic measurement of the acute response to beta-blockers.

The aim of our study was to assess whether acute variations in portal vein Doppler sonographic parameters induced by administration of a single beta-blocker agent are predictive of the long-term effects of these drugs in the prevention of a first episode of variceal bleeding. In 30 patients with liver cirrhosis at high risk for variceal bleeding, duplex Doppler sonographic parameters (maximal portal flow velocity, portal blood flow, and congestion index) were measured before and 4 h after the administration of 40 mg of propranolol. Twenty-three of these patients started chronic therapy with propanolol and were evaluated periodically (seven patients were excluded because they did not continue the therapy). The percentage of patients free from bleeding was 86.9% at the first year and 77.8% at the second year. Among a series of clinical, laboratory, and instrument-based parameters, the only one related to first bleeding, selected by the Cox regression model, was the percentage decrease in maximal portal flow velocity observed after initial administration of propranolol (P < 0.01). The best cutoff value for the percentage decrease in portal flow velocity (portal flow velocity test) was 12%. The prevalence of bleeding had been 25% (3 of 12) in patients with positive portal flow velocity test results (12% decrease or more), versus 64% (7 of 11) in patients with negative portal flow velocity test results. The actuarial probability of remaining free from bleeding (Kaplan-Meier analysis) was different in these two groups (log rank P < 0.01). The portal flow velocity test represents a safe and feasible method to predict the efficacy of beta-blockers in the prevention of a first bleeding episode in patients with cirrhosis. In patients with negative results on the portal flow velocity test, an alternative therapeutic approach should be considered.     

Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile

BACKGROUND: In recent years, the hemostatic agent recombinant factor VIIa (rFVIIa) has emerged as a potentially new therapeutic agent for management of coagulopathy in patients with cirrhosis or following severe traumatic injury, a complex problem for clinicians in which standard treatment strategies are not always effective. As with other hemostatic agents, a primary safety concern of rFVIIa therapy is the theoretical possibility that systemic administration could confer an increased risk of thrombotic complications. So far, clinical experience indicates rFVIIa to be a safe treatment for currently approved indications within hemophilia. Little information is available, however, for patient populations outside this clinical setting. STUDY DESIGN AND METHODS: This article reviews critical safety data obtained from 13 Novo Nordisk-sponsored clinical trials of rFVIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury. RESULTS: Thrombotic adverse events were reported for 5.3 percent (23/430) of placebo-treated patients and 6.0 percent (45/748) of patients on active treatment. No significant difference was found between placebo-treated and rFVIIa-treated patients with respect to the incidence of thrombotic AEs, either on an individual trial basis or for these trial populations combined (p=0.57). CONCLUSION: An important determinant for the safety profile reported here is likely to be the specific mechanism of action of rFVIIa, shown in experimental studies to be localized to the site of vascular injury where tissue factor is exposed.     

脾脏长径在无创性预测肝硬化高危食管曲张静脉出血中的临床价值

目的 研究门静脉、脾静脉内径和脾脏长径与肝硬化高危食管静脉曲张的关系及其临床价值.方法 回顾性分析望江县人民医院78例肝硬化合并食管静脉曲张住院患者的临床资料.出血组38例,非出血组40例.所有患者均行内镜确诊为食管静脉曲张.收集患者的一般资料、病因、Child-Pugh分值、肝功能生化指标（凝血酶原时间、白蛋白和胆红素水平）、是否出现腹水情况、是否有红色征,B超检测肝门静脉内径、脾静脉内径和脾脏直径.结果 两组间在红色征、肝门静脉内径、脾静脉内径和脾脏直径方面差异均有统计学意义（P均〈0.05）,出血组明显高于非出血组.结论 肝硬化食管静脉曲张破裂出血患者门静脉、脾静脉内径和脾脏长径明显增高,作为一种无创性检查指标,脾脏长径对于高危食管曲张静脉的诊断有一定的预测价值,有助于早期识别需行一级预防的肝硬化患者.     

The influence of thyroid function on the coagulation system and its clinical consequences

Summary

Several studies indicate that low plasma levels of thyroid hormone shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state, whereas high levels of thyroid hormone lead to more coagulation and less fibrinolysis. Low levels of thyroid hormone thereby seem to lead to an increased bleeding risk, whereas high levels, by contrast, increase the risk of venous thromboembolism. Hypothyroidism leads to a higher incidence of acquired von Willebrand's syndrome and with increasing levels of free thyroxine, levels of fibrinogen, factor VIII and von Willebrand factor, amongst others, increase gradually, to the extent that they may lead to symptomatic venous thromboembolism in patients with hyperthyroidism. Here, we discuss the literature on the effect of thyroid hormone on the hemostatic system and the associated risk of bleeding and venous thromboembolism. Patients with hypothyroidism are at increased risk of developing bleeding complications, which could be relevant in patients undergoing invasive procedures. Furthermore, physicians should be aware of the possibility of hyperthyroidism as an underlying risk factor for venous thromboembolism, especially in unexplained cases. Clinical studies are needed to further investigate the significance for general practice of these findings. Besides the effects of hyperthyroidism on venous thromboembolism, its effects on embolism secondary to atrial fibrillation are described.

     

How to diagnose bleeding disorders

Patients with problems of hemostasis are not uncommon in the primary care setting. The bleeding history provides critical information that helps in guiding evaluation of these patients. Results of frequently used screening tests of coagulation can be abnormal in patients who have no significant hemostatic defect and can be normal in patients who do have one.     

乙型肝炎后肝硬化患者血小板参数的临床分析

目的观察血小板参数的变化与肝硬化的关系并探讨其临床意义。方法 114例乙型肝炎后肝硬化患者分为合并上消化道出血组54例,无消化道出血组60例,另选择50例健康者作为健康对照组,将两组血小板参数进行对照比较。结果肝硬化患者血小板计数(PLT)和血小板比容(PCT)分别为(71.95±55.35)×109/L、0.08%±0.07%,与健康对照组比较,均显著降低(P<0.01),平均血小板体积(MPV)和血小板分布宽度(PDW)分别为(12.06±1.23)fL、15.92%±3.33%,比健康对照组显著升高(P<0.01);肝硬化合并上消化道出血组PLT、PCT、MPV、PDW均比无消化道出血组显著降低(P<0.05)。结论血小板参数的测定对评估肝硬化患者肝功能损害程度,判断有无出血倾向具有重要的指导意义。     

Direct oral anticoagulants: New drugs with practical problems. How can nurses help prevent patient harm?

The safe use of anticoagulants requires a delicate balance between the risk of bleeding and the risk of thrombosis, particularly in drug‐sensitive patients, such as older people. Recently‐marketed “direct oral anticoagulants” are now being increasingly prescribed and administered in the hospital setting. Direct oral anticoagulants have pharmacological properties that are often unpredictable, and inter‐patient variability in drug response is high. Therefore, people often require meticulous review and planning to ensure they receive optimal dosing and monitoring. The multidisciplinary medication management of those receiving these drugs needs to be effectively coordinated to reduce the risk of patient harm. All clinical staff, including nurses, doctors, and pharmacists, should be competent in the pharmacology of these drugs, and know which people require individualized care plans. In this study, we introduced important concepts via the use of case studies developed from commonly‐seen scenarios at our quaternary hospital. In particular, the important role of nurses in ensuring patient safety in the periprocedural setting is highlighted.     

Acute Management of Hemostasis in Patients With Neurological Injury

Neurological injuries can be divided into those with traumatic and nontraumatic causes. The largest groups are traumatic brain injury (TBI) and nontraumatic stroke. TBI patients may present with intracranial hemorrhages (contusions, or subdural or epidural hematomas). Strokes are ischemic or hemorrhagic. In all these disorders, thrombosis and hemostasis play a major role. Treatment aims to either cease bleeding and/or restore perfusion. We reviewed hemostatic and thrombolytic therapies in patients with neurological injuries by MEDLINE and EMBASE search using various key words for neurological disorders and hemostatic therapies restricted to English language and human adults. Review of articles fulfilling inclusion criteria and relevant references revealed that, in patients with ischemic stroke, intravenous thrombolytic therapy with recombinant tissue plasminogen activator within 4.5-5 hours after onset of symptoms improves clinical outcome. In contrast, there are no hemostatic therapies that are proven to improve clinical outcome of patients with hemorrhagic stroke or TBI. In patients with hemorrhagic stroke who use vitamin K antagonist or direct oral anticoagulants, there is evidence that specific reversal therapies improve hemostatic laboratory parameters but without an effect on clinical recovery. In patients with hemorrhagic stroke or TBI who use concomitant antiplatelet therapy, there is evidence for harm of platelet transfusion. In patients with aneurysmal subarachnoid hemorrhage, tranexamic acid was shown to reduce rebleeding rate without improving clinical outcome. The effects of tranexamic acid in patients with TBI are still under investigation. We conclude that, in patients with ischemic stroke, thrombolytic therapy improves outcome when given within 4.5-5 hours. In hemorrhagic stroke and TBI, most hemostatic therapies improved or corrected laboratory parameters but not clinical outcome. Currently, in several trials, the effects of tranexamic acid are being studied of which the results are eagerly awaited. Because improving clinical outcome should be the goal of new therapies, we encourage to use clinical outcome scales as the primary outcome measure in trials that investigate effects of hemostatic therapies in patients with neurological injury.     

肝硬化患者凝血、纤溶指标及血小板变化与Child-Pugh分级的关系

[目的]探讨肝硬化患者凝血、纤溶指标、血小板计数（BPC）的变化与Child-Pugh分级及上消化道出血的关系.[方法]上海市公共卫生中心2009年2月至2011年3月90例肝硬化住院患者,按Child-Pugh分级A级15例、B级46例、C级29例,分为出血组（42例）、非出血组（48例）.均检测其凝血酶原时间（PT）、凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅹ及组织纤溶酶原激活物（t-PA）、D-二聚体（D-d）、血常规,比较各组患者的相关指标.[结果]随Child-Pugh分级的增加患者PT显著延长,凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅹ、BPC逐渐降低,t-PA、D-d逐渐升高.PT、凝血因子Ⅱ、Ⅶ、BPC在Child-Pugh A、B、C组间两两比较差异有显著性;Child-Pugh B、C组凝血因子Ⅴ、Ⅹ显著高与Child-Pugh A组.出血组PT、BPC 与未出血组差异有显著性;Child B、C级肝硬化患者出血率显著高与A级,而C级病死率最高,且两两比较差异均有显著性.[结论]肝硬化患者存在明显的凝血异常及纤溶亢进,且与临床病情严重程度密切相关; PT、BPC、Child-Pugh分级可作为上消化道出血的危险因素.     

肝硬化食管静脉曲张首次破裂出血相关危险因素分析

目的:探讨肝硬化食管静脉曲张首次破裂出血的相关危险因素及其与出血联系的紧密程度,以尽早识别出高危患者。方法:回顾性分析肝硬化食管静脉曲张首次破裂出血的患者105例(观察组)及同期住院的肝硬化食管静脉曲张未破裂出血患者105例(对照组)的临床资料,先行单因素分析,再对两组间有统计学差异的指标进行多因素非条件Logistic回归分析,最后与出血联系最紧密的两个因素行双因素非条件Logistic回归分析。结果:单因素分析显示两组资料中凝血酶原时间(P0.01)、门静脉内径(P0.05)、肝功能Child分级(P0.01)、红色征(P0.01)、食管静脉曲张程度(P0.01)的差异有统计学意义,多因素非条件Logistic回归分析提示红色征(OR=2.728,P=0.016)、食管静脉曲张程度(OR=2.126,p=0.008)为出血的独立危险因素,双因素非条件Logistic回归分析提示同时存在重度食管静脉曲张和红色征与单纯重度食管静脉曲张相比较,差异有统计学意义(OR=1.812,P=0.008)。结论:红色征、食管静脉曲张程度为肝硬化食管静脉曲张首次破裂出血的独立危险因素,对预测食管静脉曲张首次破裂出血有重要的临床意义。     

No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure

Background: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high‐risk patients undergoing device‐related procedures. We sought to investigate whether continuation of warfarin sodium therapy without heparin bridging is safe and, when it is continued, the optimal international normalized ratio (INR) without increased bleeding risk at time of device‐related procedure. Methods and Results: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device‐related procedures. Patients were grouped by treatment: discontinued warfarin (?warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty‐one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than ?warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0–2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs 3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001). Conclusion: Continuation of oral anticoagulation therapy with an INR level of <2.5 does not impose increased risk of bleeding for device‐related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels. (PACE 2011; 34:868–874)