Although post-procedural bleedings are infrequent in patients with cirrhosis, they are associated with significant morbidity and mortality. Therefore, predicting and preventing such bleedings is important. Established predictors of post-procedural bleeding include high-bleeding risk procedure, severe cirrhosis and high body mass index; prognostic value of anemia, acute kidney injury and bacterial infection is more uncertain. While prothrombin time and international normalized ratio do not predict post-procedural bleeding, some evidence suggests that platelet count, whole blood thrombin generation assay and viscoelastic tests may be helpful in this context. Prevention of postprocedural bleeding involves careful management of antithrombotic drugs during the periprocedural period. Patients with cirrhosis present unique challenges due to altered pharmacokinetics and pharmacodynamics of antithrombotic drugs, but there is a lack of dedicated studies specifically focused on this patient population. Guidelines for periprocedural management of antithrombotic drugs developed for patients without liver disease are thus applied to those with cirrhosis. Some technical aspects may decrease the risk of post-procedural bleeding, namely ultrasoundguidance, opting for transjugular route rather than percutaneous route, and the level of expertise of the operator. The effectiveness of platelet transfusions or thrombopoietin-receptor agonists remains uncertain. Transfusion of fresh-frozen plasma, of fibrinogen, and administration of tranexamic acid are not recommended for reducing post-procedural bleeding in patients with cirrhosis. In conclusion, prediction of post-procedural requires a global approach taking into account the patients characteristics, the risk of the procedure, and the platelet count. There is little data to support prophylactic correction of hemostasis, and dedicated studies are needed.

This review addresses the peri-procedural bleeding risks in patients with cirrhosis, emphasizing the need for careful coagulation assessment and targeted correction strategies. Liver disease presents a unique hemostatic challenge, where traditional coagulation tests may not accurately predict bleeding risk, complicating the management of procedures like paracentesis, endoscopic therapy, and various interventional procedures. As such, this paper aims to provide a comprehensive analysis of current data, guidelines, and practices for managing coagulation in cirrhotic patients, with a focus on minimizing bleeding risk while avoiding unnecessary correction with blood products. The objectives of this review are threefold: first, to outline the existing evidence on bleeding risks associated with common invasive procedures in cirrhotic patients; second, to evaluate the efficacy and limitations of standard and advanced coagulation tests in predicting procedural bleeding; and third, to examine the role of blood product transfusions and other hemostatic interventions, considering potential risks and benefits in this delicate population. In doing so, this review highlights patient-specific and procedure-specific factors that influence bleeding risk and informs best practices to optimize patient outcomes. This review progresses through key procedures often performed in cirrhotic patients. The discussion begins with paracentesis, a low-risk procedure, followed by endoscopic therapy for varices, and concludes with high-risk interventions requiring advanced hemostatic considerations. Each chapter addresses procedural techniques, bleeding risk assessment, and evidence-based correction approaches. This comprehensive structure aims to guide clinicians in making informed, evidence-backed decisions in managing coagulation in cirrhosis, ultimately reducing procedural complications and improving care quality for this high-risk population.

The purpose of this paper is to compile and present all of the reported vascular complications that resulted from common non-vascular abdominal procedures in the literature. Non-vascular procedures include, though are not limited to, percutaneous abscess/fluid collection drainage (PAD), percutaneous nephrostomy (PN), paracentesis, percutaneous transhepatic cholangiography (PTC)/percutaneous biliary drainage (PBD), percutaneous biliary stone removal, and percutaneous radiologic gastrostomy (PG)/percutaneous radiologic gastrojejunostomy (PG-J). By gathering this information, radiologists performing these procedures can be aware of the associated vascular injuries, as well as take steps to minimize risks.

A literature review was conducted using the PubMed database to catalog relevant articles, published in the year 2000 onward, in which an iatrogenic vascular complication occurred from the following non-vascular abdominal procedures: PAD, PN, paracentesis, PTC/PBD, percutaneous biliary stone removal, and PG/PG-J. Biopsy and tumor ablation were deferred from this article.

214 studies met criteria for analysis. 28 patients died as a result of vascular complications from the analyzed non-vascular abdominal procedures. Vascular complications from paracentesis were responsible for 19 patient deaths, followed by four deaths from PTC/PBD, three from biliary stone removal, and two from PG.

Despite non-vascular percutaneous abdominal procedures being minimally invasive, vascular complications still can arise and be quite serious, even resulting in death. Through the presentation of vascular complications associated with these procedures, interventionalists can improve patient care by understanding the steps that can be taken to minimize these risks and to reduce complication rates.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Routine hemostasis parameters such as prothrombin time and fibrinogen are frequently abnormal in patients with chronic liver disease and have been demonstrated to be poor predictors for periprocedural bleeding. Alterations in procoagulant and anticoagulant factors in this population result in a state of rebalanced hemostasis, which is not reflected by routine hemostatic measures. Viscoelastic hemostatic assays (VHA) present a point of care measure of global hemostasis with an emerging role in guiding transfusion in the liver transplant setting. The potential role for VHA in guiding periprocedural transfusion is unknown. Here we critically appraise the available limited evidence on the use of VHA to guide prophylactic treatment in patients with cirrhosis undergoing procedures. We assess whether the impact of a VHA-guided approach improves clinical outcomes. Suggested areas for future research with a focus on clinically relevant outcomes, particularly periprocedural bleeding, are highlighted.

Patients with advanced liver diseases frequently acquire profound alterations in their hemostatic system. Simultaneous changes in procoagulant and anticoagulant systems result in a reset in the hemostatic balance with a relatively neutral net effect, although there are notable hypocoagulable and hypercoagulable features in the hemostatic system in patients with liver disease. Laboratory and clinical studies have demonstrated that patients have a relatively well-preserved hemostatic system even though routine diagnostic tests of hemostasis (prothrombin time, platelet count) suggest a bleeding tendency. Routine diagnostic tests of hemostasis are unsuitable to assess the hemostatic status of patients with liver disease, as these tests are insensitive for the concurrent prohemostatic and antihemostatic changes in these patients. These tests are, however, frequently requested in patients with liver disease, as they are well established indicators of severity of liver disease. This paper will discuss commonly used diagnostic and research-type hemostatic tests and will outline how test results should be interpreted in patients with liver disease.

Patients with advanced chronic liver disease (CLD) often need procedures to both treat and prevent complications of portal hypertension such as ascites or gastrointestinal bleeding. Abnormal results for hemostatic tests, such as prolonged prothrombin time, international normalized ratio, and/or thrombocytopenia, are commonly encountered, raising concerns about increased bleeding risk and leading to transfusion to attempt to correct prior to interventions. However hemostatic markers are poor predictors of bleeding risk in CLD, and routine correction, particularly with fresh frozen plasma and routine platelet transfusions, should be avoided. This narrative review discusses the hemostatic management of patients with CLD using 2 case descriptions.

Optimal blood product transfusion strategies before tunneled central venous catheter (CVC) placement are required in critically ill coagulopathic patients with liver disease to reduce exposure to allogeneic blood products and mitigate bleeding and thrombotic complications.

This study evaluated the safety and efficacy of a thromboelastography-guided transfusion strategy for the correction of coagulopathy in patients with liver disease compared with a conventional transfusion strategy (using international normalized ratio, platelet count, and fibrinogen) before tunneled CVC insertion.

A retrospective propensity score-matched single-center cohort study was conducted at a quaternary care academic medical center involving 364 patients with liver disease (cirrhosis and acute liver failure) who underwent tunneled CVC insertion in the ICU. Patients were stratified into two groups based on whether they received blood product transfusions based on a thromboelastography-guided or conventional transfusion strategy.

Primary outcomes that were evaluated included the volume, units and cost of blood products (fresh frozen plasma, cryoprecipitate, and platelets) when using a thromboelastography-guided or conventional approach to blood transfusions. Secondary outcomes included the frequency of procedure-related bleeding and thrombotic complications.

The total number of units/volume/cost of fresh frozen plasma (12 U/3,000 mL/$684 vs. 32 U/7,500 mL/$1,824 [p = 0.019]), cryoprecipitate (60 U/1,500 mL/$3,240 vs. 250 U/6,250 mL/$13,500 [p < 0.001]), and platelets (5 U/1,500 mL/$2,610 vs. 13 units/3,900 mL/$6,786 [p = 0.046]) transfused were significantly lower in the thromboelastography-guided transfusion group than in the conventional transfusion group. No differences in the frequency of bleeding/thrombotic events were observed between the two groups.

A thromboelastography-guided transfusion strategy for correction of coagulopathy in critically ill patients with liver disease before tunneled CVC insertion, compared with a conventional transfusion strategy, reduces unnecessary exposure to allogeneic blood products and associated costs without increasing the risk for peri-procedural bleeding and thrombotic complications.

Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors.

Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers.

A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31).

Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

Advanced chronic liver disease is accompanied with relevant changes in the corpuscular and plasmatic coagulation system. Due to thrombocytopenia that is regularly observed in these patients, platelet transfusions are often performed prior invasive procedures to prevent possible bleeding complications. However, platelet transfusions are associated with clinically significant adverse events and economically relevant health care costs. Thus, avoiding unnecessary platelet transfusions remains pivotal in daily clinical practice. The first step is to carefully check if increasing platelet counts prior to a planned invasive procedure is really necessary. Nowadays, two well-tolerated thrombopoetin-receptor agonists (TPO-RAs), Avatrombopaq and Lusutrombopaq, to treat thrombocytopenia preemptively before an invasive procedure in patients with liver cirrhosis are available. This review provides a guide for clinician when to increase platelet counts prior an invasive procedure in patients with liver cirrhosis and helps to identify situations in which the use of TPO-RA may be reasonable.

To investigate the relationship between thrombin-antithrombin complex (TAT), plasmin-α 2-plasmininhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (tPAIC) and postoperative complications in the early stage after liver transplantation (LT).

We analyzed the perioperative clinical data, including plasma TAT, PIC, sTM, and tPAIC, of 130 post-LT patients admitted to the intensive care unit (ICU), West China Hospital, Sichuan University between December 2021 and November 2022. Patients were divided into two groups, a complication group and a non-complication group, according to whether they experienced complications of Clavien-Dindo (CD) grade Ⅲb and above within 30 days after the surgery. Univariate analysis and binary multivariate logistic regression models were used to determine the risk factors for complications within 30 days post-LT.

The incidence of complications of CD grade Ⅲb and above within 30 days post-LT was 33.1% (43/130). Patients in the complication group had significantly higher scores for the Model for End-Stage Liver Disease (MELD), operative time, intraoperative red blood cell transfusion volume, intraoperative plasma transfusion volume, and plasma TAT, PIC, sTM and tPAIC measured at the time of admission to ICU after the operation than those in the non-complication group did (all P<0.05). Logistic regression showed that for every single U of red blood cells transfused during the transplant surgery, the probabilities of complications within 30 days post-LT increased by 15.1% (95% confidence interval [ C I]: 1.070-1.239, P<0.001) and for the increase of every single TU/mL of plasma sTM measured upon post-LT admission to ICU, the probabilities of complications increased by 13.7% (95% CI: 1.060-1.220, P<0.001).

Plasma sTM measured upon admission to ICU after LT is an independent risk factor for complications within 30 days post-LT, and additional assessment of sTM may help predict complications in the early stage post-LT.

As ultrasound-guided percutaneous liver biopsy (PLB) has become a standard and important method in the management of liver disease in our country, a periodical audit of the major complications is needed.

To determine the annual incidence of major complications following ultrasound-guided PLB and to identify variables that are significantly associated with an increased risk of major complications.

A total of 1857 consecutive cases of PLB were included in our hospital from January 2021 to December 2021. The major complication rate and all-cause 30-d mortality rate were determined. Multivariate analyses were performed by logistic regression to investigate the risk factors associated with major complications and all-cause 30-d mortality following ultrasound-guided PLB.

In this audit of 1857 liver biopsies, 10 cases (0.53%) of major complications occurred following ultrasound-guided PLB. The overall all-cause mortality rate at 30 d after PLB was 0.27% (5 cases). Two cases (0.11%) were attributed to major hemorrhage within 7 d after liver biopsy. Fibrinogen less than 2 g/L [odds ratio (OR): 17.226; 95% confidence interval (CI): 2.647-112.102; P = 0.003], post-biopsy hemoglobin level (OR: 0.963; 95%CI: 0.942-0.985; P = 0.001), obstructive jaundice (OR: 6.698; 95%CI: 1.133-39.596; P = 0.036), application of anticoagulants/antiplatelet medications (OR: 24.078; 95%CI: 1.678-345.495; P = 0.019) and age (OR: 1.096; 95%CI: 1.012-1.187; P = 0.025) were statistically associated with the incidence of major complications after PLB.

In conclusion, the results of this annual audit confirmed that ultrasound-guided PLB can be performed safely, with a major complication rate within the accepted range. Strict patient selection and peri-biopsy laboratory assessment are more important than procedural factors for optimizing the safety outcomes of this procedure.

Much has evolved over the past 25 years regarding our understanding of the coagulopathy of liver disease. Paradoxically, this form of coagulopathy is relatively hypercoagulability despite the common clinical impression of a hemorrhagic tendency. The latter is largely driven by portal-mesenteric venous pressure (ie, portal hypertension) and has little to do with hemostatic pathways. It cannot be emphasized enough that the INR does not offer a meaningful measure in this situation and may lead to interventions such as fresh frozen plasma that can actually worsen portal pressure and hence pressure-driven bleeding. With regard to procedure-related bleeding, we point out substantial differences in the definition of high-risk procedures and propose a new operational definition dependent on the applicability of local hemostatic measures, although this requires further investigation. The common occurrence of venous thrombosis in these patients requires careful consideration of hemostatic pathways and overall risk and benefit of intervention. The decision regarding anticoagulation therapy needs to be driven not only by a global assessment including history of non-portal hypertensive-related bleeding, but also by fall risk which can result in head trauma in patients prone to encephalopathy. This is probably best estimated by frailty but has yet to be adequately investigated. In the background of these concerns, several superimposed and complex conditions including infections and renal dysfunction should be taken into account. Inherited forms of thrombophilia in the setting of cirrhosis perhaps do not outweigh the thrombophilia inherent to liver disease but warrant further consideration.

Cardiac ascites is a classical finding of right-sided heart failure, mainly caused by tricuspid valve disease and constrictive pericarditis. Refractory cardiac ascites, defined as ascites that is uncontrollable with any medication, including conventional diuretics and selective vasopressin V2 receptor antagonists, is a rare but challenging entity. Although cell-free and concentrated ascites reinfusion therapy (CART) is a therapeutic option for refractory ascites in patients with liver cirrhosis and malignancy, its efficacy in cardiac ascites has never been reported. We herein report a case of CART for refractory cardiac ascites in a patient with complex adult congenital heart disease (ACHD).

A 43-year-old Japanese female with a history of ACHD involving single ventricle haemodynamics presented with refractory massive cardiac ascites due to progressive heart failure. Because conventional therapy using diuretics could not control her cardiac ascites, abdominal paracentesis was frequently required, resulting in hypoproteinaemia. Therefore, CART was initiated once per month in addition to conventional therapies, which enabled the prevention of hypoproteinaemia and further hospitalizations except to undergo CART. In addition, it helped improve her quality of life without any complications for 6 years until she died from cardiogenic cerebral infarction at the age of 49 years.

This case demonstrated that CART can be safely performed in patients with complex ACHD and refractory cardiac ascites due to advanced heart failure. Thus, CART may improve refractory cardiac ascites as effectively as massive ascites caused by liver cirrhosis and malignancy and lead to an improvement in the patients' quality of life.

Hospitalised patients with decompensated cirrhosis are in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic pathways. However, this rebalanced haemostatic state is highly susceptible to perturbations and may easily tilt towards hypocoagulability and bleeding. Acute kidney injury, bacterial infections and sepsis, and progression from acute decompensation to acute-on-chronic liver failure are associated with additional alterations of specific haemostatic pathways and a higher risk of bleeding. Unfortunately, there is no single laboratory method that can accurately stratify an individual patient's bleeding risk and guide pre-procedural prophylaxis. A better understanding of haemostatic alterations during acute illness would lead to more rational and individualised management of hospitalised patients with decompensated cirrhosis. This review will outline the latest findings on haemostatic alterations driven by acute kidney injury, bacterial infections/sepsis, and acute-on-chronic liver failure in these difficult-to-treat patients and provide evidence supporting more tailored management of bleeding risk.

Patients with cirrhosis are at risk of both thrombotic and hemorrhagic events. Traditional hemostatic tests are inadequate to assess the complex and fragile balance of hemostasis in this setting, especially in advanced stages of disease such as decompensated cirrhosis or acute on chronic liver failure (ACLF). Furthermore, the indiscriminate use of pro-hemostatic agents for prophylaxis and treatment of bleeding episodes is still debated and often contraindicated. Alongside, splanchnic, and peripheral thrombotic events are frequent in this population and require management that involves a careful balance between risks and benefits of antithrombotic therapy.

This review aims to address the state of the art on the clinical management of the hemostatic balance of cirrhosis in terms of established knowledge and future challenges.

The old paradigm of cirrhosis as a naturally anticoagulated condition has been challenged by more sophisticated global tests of hemostasis. Integrating this information in the clinical decision-making is still challenging for physicians and experts in hemostasis.

Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding.

Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFR_Scr, eGFR_CysC, and eGFR_Scr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed.

Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFR_Scr, eGFR_CysC, eGFR_Scr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFR_Scr, eGFR_CysC, eGFR_Scr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death.

AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

This randomized controlled trial (RCT) was conducted with the aim to evaluate the efficacy and safety of using ROTEM-based transfusion strategy in cirrhotic children undergoing invasive procedures.

This was an open-label, RCT which included (i) children under 18 years of age with liver cirrhosis; (ii) INR between 1.5 and 2.5; and/or (iii) platelet count between 20 × 10⁹ /L and 50 × 10⁹ /L (for procedures other than liver biopsy) and between 40 × 10⁹ /L and 60 × 10⁹ /L (for liver biopsy); and (iv) listed for invasive procedures. Stratified randomization was done for children undergoing liver biopsies. Patients randomized to the ROTEM and conventional groups received blood component transfusion using predefined criteria.

A total of 423 invasive procedures were screened for inclusion of which 60 were randomized (30 in each group with comparable baseline parameters). The volume of total blood components, fresh frozen plasma (FFP) and platelets transfused was significantly lower in ROTEM as compared to conventional group. Only 46.7% of children in ROTEM group received a blood component compared to 100% in conventional group (p < .001). The requirement of FFP (ROTEM: 43.3%, Conventional: 83.3%, p = .001) was significantly lower in the patients receiving ROTEM-guided transfusions. There was no difference in procedure-related bleed and transfusion-related complications between the two groups. ROTEM was cost-effective (p = .002) despite the additional cost of the test.

ROTEM-based transfusion strategies result in lower blood component transfusion in cirrhotic children undergoing invasive procedures without an increase in risk of procedure-related bleed. ROTEM-guided transfusion strategy is cost-effective.

Patients with acute and chronic liver disease present with a wide range of disease states and severity that may require liver transplantation (LT). Physiologic alterations occur that are dynamic throughout all phases of perioperative care, creating complex management scenarios that necessitate multidisciplinary clinical care. Specifically, alterations in hemostasis in liver disease can be pronounced and evolve with disease progression over time. Recent studies and society guidance address this emerging paradigm and offer recommendations to assist with hemostatic management in patients with liver disease. However, patients undergoing LT are unique and diverse, often with unstable disease that requires specialized approaches. Our aim is to provide a focused review of hemostatic management of the LT patient, distinguish unique aspects of the three main phases of care (before LT, perioperative, and after LT), and identify knowledge gaps and critical areas of future research.

Acute kidney injury (AKI) patients have increased bleeding risk, which could be partially due to acquired platelet dysfunction. We conducted a systematic review and a cohort study to investigate platelet function and count in AKI and their association with AKI-related bleeding and mortality. Through a systematic literature search in PubMed and Embase, we identified 9 studies reporting platelet function and 56 studies reporting platelet count or platelet indices in AKI patients. Overall, platelet aggregation was reduced in AKI patients in nonintensive care unit (ICU) settings but not in ICU settings, except that reduced aggregation was associated with renal replacement therapy. Thrombocytopenia in AKI was frequent and often predictive of mortality. In our cohort study, we prospectively included 54 adult ICU patients who developed AKI within 24 hours of ICU admission and 33 non-AKI ICU controls. Platelet function was measured with light transmission aggregometry and flow cytometry. AKI patients bled more frequently than non-AKI patients (p = 0.04), and bleeding was associated with increased 30-day mortality in AKI (p = 0.02). However, platelet function was not different between AKI and non-AKI patients (aggregation: all p > 0.52; flow cytometry: all p > 0.07) and platelet function was not associated with bleeding in AKI. In conclusion, a reduced platelet count is frequent in AKI, but the literature on platelet function in AKI is sparse. In a cohort study, we demonstrated that patients with AKI within 24 hours of ICU admission exhibited increased bleeding tendency but this was not associated with reduced platelet function.

Bacterial infections in cirrhosis are associated with increased bleeding risk. To assess the factors responsible for bleeding tendency in patients with bacterial infections, we conducted a prospective study comparing all 3 aspects of hemostasis (platelets, coagulation, and fibrinolysis) in hospitalized patients with decompensated cirrhosis with vs. without bacterial infections.

Primary hemostasis assessment included whole blood platelet aggregation and von Willebrand factor (VWF). Coagulation assessment included procoagulant factors (fibrinogen, factor II, V, VII, VIII, IX, X, XI, XII, XIII), natural anticoagulants (protein C, protein S, antithrombin) and thrombomodulin-modified thrombin generation test. Fibrinolysis assessment included fibrinolytic factors (plasminogen, t-PA, PAI-1, α2-AP, TAFIa/ai) and plasmin-antiplasmin complex (PAP).

Eighty patients with decompensated cirrhosis were included (40 with and 40 without bacterial infections). Severity of cirrhosis and platelet count were comparable between groups. At baseline, patients with cirrhosis and bacterial infections had significantly lower whole blood platelet aggregation, without significant differences in VWF. Regarding coagulation, bacterial infections were associated with reduced procoagulant factors VII and XII, and a significant reduction of all natural anticoagulants. However, thrombomodulin-modified thrombin generation was comparable between the study groups. Finally, although mixed potentially hypo-fibrinolytic (lower plasminogen) and hyper-fibrinolytic (higher t-PA) changes were present in bacterial infections, a comparable level of PAP was detected in both groups. Upon resolution of infection (n = 29/40), platelet aggregation further deteriorated whereas coagulation and fibrinolysis factors returned to levels observed in patients without bacterial infections.

In hospitalized patients with decompensated cirrhosis, bacterial infections are associated with reduced whole blood platelet aggregation and a significant decrease of all natural anticoagulants, which may unbalance hemostasis and potentially increase the risk of both bleeding and thrombosis.

Bacterial infections are a common issue in hospitalized patients with decompensated cirrhosis (i.e. patients hospitalized due to severe complications of advanced chronic liver disease). Patients with decompensated cirrhosis who acquire infections may be at increased risk of bleeding complications following invasive procedures (that is a procedure in which the body is penetrated or entered, for instance by a needle or a tube). As bleeding complications in decompensated cirrhosis are associated with a high risk of further decompensation and death, there is an urgent need to understand the factors responsible for such increased bleeding tendency. Herein, we investigated the alterations of hemostasis (that is the physiological process responsible for clot formation and stability) in patients with decompensated cirrhosis and bacterial infections. We found that development of bacterial infections in these patients is associated with alterations of hemostasis (particularly of platelets and clotting cascade) that may increase the risk of both bleeding and thrombotic complications.

The prevention and management of bleeding and thrombosis in patients with cirrhosis poses several difficult clinical questions. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics, including current views on haemostasis in liver disease, controversy regarding the need to correct thrombocytopenia and abnormalities in the coagulation system in patients undergoing invasive procedures, and the need for thromboprophylaxis in hospitalised patients with haemostatic abnormalities. Multiple recommendations in this document are based on interventions that the panel feels are not useful, even though widely applied in clinical practice.

Prolonged prothrombin time and thrombocytopenia are common in patients with cirrhosis. These parameters do not reflect the overall hemostatic rebalance or bleeding risk in the periprocedural setting; however, attempts to correct these parameters remain frequent. We review the literature on periprocedural bleeding risk, bleeding risk factors, and the risk and benefits of hemostatic interventions in patients with cirrhosis. We provide guidance recommendations on evaluating bleeding risk in this patient group and management of hemostatic abnormalities in the periprocedural setting.

The combination of frequently abnormal hemostatic markers and catastrophic bleeding as seen with variceal hemorrhage has contributed to the longstanding misperception that chronic liver disease (CLD) constitutes a bleeding diathesis. Laboratory studies of hemostasis in liver disease consistently challenge this with global coagulation assays incorporating activation of the protein C pathway demonstrating rebalanced hemostasis. It is now recognized that bleeding in CLD is predominantly secondary to portal hypertension (rather than a coagulopathy) and additionally that these patients are at increased risk of venous thrombosis, particularly in the portal venous system. This narrative review describes the current understanding of hemostasis in liver disease, as well as the periprocedural management of hemostasis and anticoagulation for management of venous thromboembolism in patients with CLD.

Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease.

To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI).

We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI.

Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8-10.7]), MELD (OR 1.13 [95%CI 1.02-1.27]), any bleeding (OR 9.07 [95%CI 2.02-40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02-1.07]) were independently associated with 30-day mortality.

AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.

Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure-related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post-procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.

Gaps of knowledge still exist about the potential association between severe thrombocytopenia and increased risk of procedure-associated bleeding in patients with liver disease.

In this narrative review, we aimed at examining the association between procedure-related bleeding risk and platelet count in patients with cirrhosis and severe thrombocytopenia in various settings. We updated to 2020 a previously conducted literature search using MEDLINE/PubMed and EMBASE. The search string included clinical studies, adult patients with chronic liver disease and thrombocytopenia undergoing invasive procedures, any interventions and comparators, and haemorrhagic events of any severity as outcome.

The literature search identified 1276 unique publications, and 15 studies met the inclusion criteria and were analysed together with those identified by the previous search. Most of the new studies included in our analysis did not assess the association between post-procedural bleeding risk and platelet count alone in patients with chronic liver disease. Furthermore, some results could have been biased by prophylactic platelet transfusions. A few studies found that severe thrombocytopenia may be predictive of bleeding following percutaneous liver biopsy, dental extractions, percutaneous ablation of liver tumours and endoscopic polypectomy.

Currently available literature cannot support definitive conclusions about the appropriate target platelet counts to improve the risk of bleeding in cirrhotic patients who underwent invasive procedures; moreover, it showed enormous variability in the use of prophylactic platelet transfusions.

In patients with decompensated cirrhosis, procedure-related bleeding is a potentially lethal complication. Routine coagulation tests such as international normalized ratio and platelet count do not predict bleeding risk. We investigated whether thromboelastography (TEG) can identify patients with cirrhosis who are at risk of procedure-related bleeding. As a part of a prospective study on hemostasis in decompensated cirrhosis, patients had TEG performed on admission and were followed prospectively during hospitalization for the development of procedure-related bleeding. Eighty patients with cirrhosis were included. Among the 72 who had procedures performed, 7 had procedure-related bleeding, which was major in three cases (two following paracentesis and one following thoracentesis). Conventional coagulation tests were comparable between bleeding and nonbleeding patients, whereas TEG parameters of k-time (4.5 minutes vs. 2.2 minutes; P = 0.02), α-angle (34° vs. 59°; P = 0.003), and maximum amplitude (37 mm vs. 50 mm; P = 0.004) were significantly different (all indicative of hypocoagulability). TEG maximum amplitude (MA), a marker of overall clot stability, accurately discriminated between patients who had major, life-threatening bleeding (all with MA < 30 mm) and those who had mild or no bleeding (all with MA > 30 mm), whereas a platelet count < 50 × 109/L could not discriminate between bleeding (minor or major) and nonbleeding patients. Conclusion: In a prospective cohort of hospitalized patients with decompensated cirrhosis, TEG parameters associated with hypocoagulability appeared to predict procedure-related bleeding, particularly a TEG MA < 30 mm. If results are validated in a larger cohort, this could be a threshold to identify patients with decompensated cirrhosis at higher risk for procedure-related bleeding, in whom to consider preprocedural prophylaxis.

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.

In emergency medicine and intensive care the key to control active bleeding - besides definitive therapy (endoscopy, therapeutic angiography or operation) - often is to improve the patients clotting and thrombus formation. Knowledge about routine laboratory testing, their strength and weaknesses as well as indications and dosing of pro-coagulants and blood products remains pivotal in these situations. Achieving hemostasis can be especially challenging in patients with liver cirrhosis, innate or acquired coagulation disorders. This review summarizes the principles of hemostasis diagnostics and management in acute bleeding for gastroenterologists and hepatologists including novel available antidotes and innovative tools for patients with advanced liver disease such as thromboelastometry.

Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI.

Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated.

In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis.

Liver biopsy is required when clinically important information about the diagnosis, prognosis or management of a patient cannot be obtained by safer means, or for research purposes. There are several approaches to liver biopsy but predominantly percutaneous or transvenous approaches are used. A wide choice of needles is available and the approach and type of needle used will depend on the clinical state of the patient and local expertise but, for non-lesional biopsies, a 16-gauge needle is recommended. Many patients with liver disease will have abnormal laboratory coagulation tests or receive anticoagulation or antiplatelet medication. A greater understanding of the changes in haemostasis in liver disease allows for a more rational, evidence-based approach to peri-biopsy management. Overall, liver biopsy is safe but there is a small morbidity and a very small mortality so patients must be fully counselled. The specimen must be of sufficient size for histopathological interpretation. Communication with the histopathologist, with access to relevant clinical information and the results of other investigations, is essential for the generation of a clinically useful report.