Blood conservation strategies in liver transplantation: Past, present, and future

Abstract

Liver transplantation (LT) is a complex surgical procedure often accompanied by massive intraoperative blood loss, necessitating transfusion of blood and blood products. However, transfusion of allogeneic blood has been consistently associated with adverse outcomes, including increased post-transplant morbidity and mortality, higher rates of infection, acute kidney injury, and reduced graft survival. Allogeneic blood transfusion also exerts immunomodulatory effects that may influence both short- and long-term outcomes, including graft rejection and recurrence of malignancy. Consequently, the development and implementation of effective blood conservation strategies (BCS) have become integral to improving perioperative outcomes in LT recipients. Blood conservation is defined as a patient-centered, evidence-based approach that aims to minimize exposure to allogeneic blood products while ensuring adequate oxygen delivery and hemostasis. The concept encompasses a continuum of interventions beginning in the preoperative period and extending through intraoperative and postoperative management. Preoperative optimization is the cornerstone of modern BCS. Detecting and correcting anemia, thrombocytopenia, and coagulopathy prior to surgery can significantly reduce transfusion needs. Intraoperatively, minimizing iatrogenic blood loss through careful dissection, low central venous pressure anesthesia, and maintenance of normothermia are key components. Acute normovolemic hemodilution (ANH) and intraoperative cell salvage (ICS) enable the collection, washing, and reinfusion of shed autologous red cells, which has been shown to be both safe and effective in LT. The combination of ANH and ICS forms a synergistic approach to intraoperative blood conservation. The use of viscoelastic point-of-care coagulation testing (such as thromboelastography or rotational thromboelastometry) has revolutionized intraoperative transfusion decision-making by allowing goal-directed correction of coagulopathy, thereby avoiding empiric transfusion. Enhanced recovery protocols that facilitate rapid correction of coagulopathy, early nutrition, and reduced infection rates also indirectly reduce transfusion requirements. Looking toward the future, advances in blood substitutes, artificial oxygen carriers, and pharmacologic agents targeting endothelial stabilization and coagulation balance hold promise for further reducing transfusion dependency. Integration of machine learning models for individualized prediction of transfusion needs, along with standardized institutional blood management programs, could transform perioperative care in LT.

Key Words: Liver transplantation; Blood transfusion; Patient blood management; Hemostasis; Antifibrinolytic agents

Core Tip: Blood conservation in liver transplantation is critical to reduce transfusion-related morbidity, cost, and immunological complications. Effective strategies begin preoperatively with optimization of anemia, correction of coagulopathy, and patient selection. Intraoperative measures include low central venous pressure anesthesia, meticulous surgical technique, use of cell salvage, point-of-care coagulation monitoring, and targeted component therapy rather than empirical transfusion. Pharmacological adjuncts such as antifibrinolytics further reduce blood loss. Postoperatively, restrictive transfusion thresholds and ongoing hemostatic monitoring are essential. A multidisciplinary, protocol-driven approach significantly improves outcomes and graft survival.

INTRODUCTION

Liver transplantation (LT) has become an established and often definitive therapeutic intervention for a wide range of life-threatening hepatic disorders. Over subsequent decades, significant improvements in perioperative care-including technical refinements in hepatectomy and graft implantation, enhanced preoperative clinical optimization, advances in intraoperative monitoring and anesthetic strategies, evolution in immunosuppressive regimens, and structured postoperative management protocols-have collectively contributed to notable gains in patient outcomes. Despite these advancements, perioperative blood loss and transfusion requirements remain pivotal determinants of morbidity, mortality, graft function, and resource utilization in LT[1]. Allogeneic blood transfusion (ABT) has both clinical and financial implications. ABT is associated with transfer for disease transmission. It negatively hampers patients post-operative recovery by increasing infectious and pulmonary complications. It is also associated with transfusion-related immune modulation which results in poor long-term outcome. Given the complex coagulopathy inherent in end-stage liver disease (ESLD) and the hemodynamic challenges of major hepatic surgery, a structured, evidence-driven approach to blood conservation has emerged as a central component of modern perioperative practice. In this narrative review, we describe blood conservation strategies (BCS) across the perioperative continuum, structured into pre-operative, intra-operative, and post-operative phases. Pre-operative strategies focus on patient optimization and include patient blood management (PBM), correction of pre-operative anemia, and management of coagulopathy. Intra-operative strategies aim to minimize blood loss and transfusion requirements and encompass intra-operative cell salvage, low central venous pressure (CVP) anesthesia, acute normovolemic hemodilution (ANH), use of pharmacologic agents (e.g., antifibrinolytics), and the application of advanced energy devices and surgical adjuncts to reduce intra-operative bleeding. Post-operative strategies are directed toward preventing ongoing blood loss and optimizing recovery, and include continued PBM principles, goal-directed fluid management, early detection and correction of post-operative anemia, judicious use of blood transfusion based on restrictive thresholds, meticulous drain and wound management, optimization of coagulation status, and early mobilization and nutritional support to enhance hematologic recovery. In this narrative review, we discuss various modalities that can be utilized to reduce blood transfusion in LT.

SEARCH METHODS

We reviewed published literature on LT and BCS between 2015 and 2025 from online search engines PubMed and MEDLINE using the search terms LT, BCSs, PBM and Boolean operators like “AND, OR, and NOT”. We included only those publications relevant to BCS. Secondary sources retrieved from these publications were identified through manual searches and assessed for relevance.

RESULTS

Blood conservation in LT can be systematically conceptualized across distinct phases: The pre-operative phase, which focuses on the identification and correction of anemia and coagulopathy, with optimization using PBM principles. Intraoperative strategies such as surgical strategies, anesthesia and hemostasis management lead to a reduction of blood loss through refined operative techniques. The postoperative or recovery phase, is where restrictive transfusion thresholds, targeted correction, and mitigation of secondary coagulopathy are carried out.

PRE-OPERATIVE PHASE

Optimization in LT using PBM principles

In LT, PBM is a patient-centered, evidence-based, multidisciplinary bundle of care that aims to optimize hemoglobin (Hb) and hemostasis, minimize blood loss, and preserve the patient’s own blood across the transplant continuum in order to improve recipient and graft outcomes while reducing transfusion-related harm[2]. Table 1 outlines the various pillars of PBM[3].

Table 1 Phase-integrated, three-pillar, 9 matrix framework spanning the pre-, intra-, and post-transplant periods.

Phase of care	Pillar 1: Red cell mass optimization	Pillar 2: Blood loss minimization	Pillar 3: Anemia tolerance optimization
Pre-transplant	Screen all candidates for anemia early in transplant evaluation. Identify and correct iron, vitamin B12, and folate deficiencies. Treat inflammation- or renal-related anemia where feasible. Avoiding unnecessary pre-transplant transfusions that may increase sensitization and complications	Perform structured bleeding risk assessment (portal hypertension, coagulopathy, thrombocytopenia). Optimize coagulation status without prophylactic plasma or platelet transfusion. Plan surgical and anesthetic strategies anticipating high-risk bleeding	Assess cardiopulmonary reserve and end-organ function. Optimize oxygen delivery (nutrition, respiratory function, cardiac status). Educate the team on restrictive transfusion thresholds
Intra-operative	Avoiding prophylactic or trigger-based transfusion without physiologic indication. Using goal-directed transfusion guided by viscoelastic testing. Preserve autologous red cell mass wherever feasible	Employ meticulous surgical technique and low-CVP anesthesia. Use antifibrinolytics when indicated. Apply viscoelastic coagulation monitoring (TEG/ROTEM) to guide hemostatic therapy. Consider cell salvage where appropriate	Accept lower hemoglobin levels with stable hemodynamics and adequate oxygenation. Maintain normothermia, acid-base balance, and adequate perfusion. Base transfusion decisions on physiologic parameters rather than laboratory values alone
Post-transplant	Support erythropoiesis through nutritional supplementation. Treat ongoing anemia causes (renal dysfunction, inflammation, infection). Minimize phlebotomy-related blood loss	Monitor closely for surgical site bleeding and coagulopathy. Avoid routine correction of abnormal coagulation tests without clinical bleeding. Use targeted hemostatic therapy if bleeding occurs	Follow restrictive transfusion strategies in the ICU and ward. Optimize oxygenation, ventilation, and hemodynamic support. Avoid transfusion-related complications that may impair graft function

CVP: Central venous pressure; ICU: Intensive care unit; TEG: Thromboelastography; ROTEM: Rotational thromboelastometry.

Preoperative optimization

Adequate circulating blood volume is a cornerstone of preoperative optimization, as it plays a critical role in reducing both intraoperative and postoperative complications. The evolving discipline of Perioperative Medicine has stated that anemia remains frequently underdiagnosed and insufficiently managed before surgery. Robust evidence demonstrates that preoperative anemia is independently associated with adverse surgical outcomes, including prolonged hospitalization, higher rates of postoperative complications, myocardial ischemia, infections, and increased overall morbidity and mortality[4,5].

Transfusion practices, from historic times, have favored a liberal strategy, targeting Hb levels of 8-10 g/dL or higher to optimize oxygen delivery[6]. However, accumulating evidence has demonstrated that a restrictive transfusion strategy-typically using a Hb threshold of approximately 7 g/dL-is safer and equally, if not more, effective in hemodynamically stable, non-cardiac patients[7]. In line with this evidence, the American Association of Blood Banks recommends reserving red blood cell (RBC) transfusions for stable patients who meet restrictive thresholds, generally between Hb 7 and 8 g/dL[7]. In contrast, patients with underlying cardiovascular disease may benefit from a higher transfusion trigger, with Hb levels maintained above 8 g/dL[8]. Consequently, clinicians must judiciously balance the potential risks and benefits when considering blood transfusion on an individual basis.

Understanding pre-operative anemia

The World Health Organization defines anemia as Hb < 13 g/dL in men and < 12 g/dL in women; however, these thresholds may not adequately reflect perioperative risk. Female patients have lower circulating blood volume, so equivalent surgical blood loss represents a greater proportion of red cell mass, increasing their risk of perioperative transfusions and related complications if lower hemoglobin targets are accepted[9,10]. Studies indicate that preoperative Hb < 13 g/dL is associated with higher morbidity, mortality, and transfusion rates irrespective of sex[11]. Therefore, a Hb threshold of 13 g/dL is recommended for defining preoperative anemia in both men and women in high-blood-loss procedures.

Evidence-based rationale for restrictive transfusion and anemia optimization in LT

Evidence from transfusion-declining surgical cohorts demonstrates a clear, dose-dependent relationship between falling Hb levels and mortality, with a marked inflection point at Hb concentrations below 6 g/dL, while postoperative levels of 7-8 g/dL are generally well tolerated, thereby defining physiologic limits that support restrictive transfusion practices in LT rather than prophylactic red cell use[12,13]. These findings are reinforced by physiologic studies in healthy volunteers showing reversible myocardial ischemia, fatigue, and cognitive changes at Hb levels between 5 g/dL and 7 g/dL, underscoring that clinically meaningful impairment precedes life-threatening decompensation and that transfusion decisions should be guided by clinical context rather than numeric thresholds alone[14-16]. Also, the reticulocyte index can be used to treat anemia in the preoperative phase (Table 2). Data in elderly and cardiac patients suggest variable anemia tolerance, with acceptable hemodilution to Hb levels of approximately 8.8-9.9 g/dL in controlled settings, while large population studies indicate that even mild anemia is associated with increased perioperative morbidity and mortality, emphasizing the importance of early pre-transplant anemia identification and optimization[17-19]. Observational studies consistently associate red cell transfusion with increased risks of infection, acute respiratory distress syndrome, multiorgan dysfunction, and mortality, although these findings are limited by confounding related to illness severity, highlighting the need for evidence-based transfusion strategies in the immunocompromised liver transplant population[20,21]. Randomized clinical trials, including surgical studies and the Transfusion Requirements in Critical Care trial, demonstrate no survival benefit with liberal transfusion thresholds and, in some cases, reduced cardiopulmonary complications with restrictive strategies, findings further supported by meta-analyses showing substantial reductions in red cell utilization without increased mortality[22-27]. Collectively, this body of evidence underpins contemporary BCS in LT by validating restrictive, patient-specific transfusion approaches, prioritizing preoperative anemia correction, and guiding future precision-based transfusion practices as ongoing trials continue to refine risk stratification in high-risk surgical populations[28]. Table 3 details the various screening methods and optimization strategies[29-56].

Table 2 Reticulocyte production index integrated approach for anemia.

RPI < 2	RPI > 2
Hypoproliferative	Adequate production
Workup:	Look for bleeding/hemolysis
Iron studies, B12/folate	Transfusion strategies
Treat deficiency	Bleeding management
Recheck RPI	Transplant readiness, optimize Hb

RPI = [(HCT/45) × RET%]/maturation time. RPI: Reticulocyte production index; Hb: Hemoglobin; B12: Vitamin B12.

Table 3 Pre-operative phase screening and optimization.

Pre LT screening	Optimization
Uniform-anemia threshold (Hb < 13 g/dL)[29-31]	Recent literature supports revising the definition of preoperative anemia for patients undergoing high–blood-loss surgery. Although traditional criteria use sex-specific hemoglobin thresholds, evidence shows that a preoperative hemoglobin level below 13 g/dL is associated with higher transfusion rates, morbidity, and mortality irrespective of sex. Therefore, a hemoglobin cutoff of 13 g/dL is recommended to define preoperative anemia in both men and women in this surgical setting
Serial Hb monitoring to be advised only when indicated[32,33]	Standardized order sets that mandate routine blood draws, despite limited evidence supporting their clinical utility may lead to unnecessary investigations, increased healthcare costs, and iatrogenic blood loss, without demonstrable improvement in patient outcomes or reductions in length of hospital stay therefore, needs to be avoided
Detailed bleeding and transfusion history[34-36]	National blood collection and utilization survey report 2007, indicates that approximately 40%-70% of all red blood cell transfusions occur in surgical patients. Consequently, a thorough understanding of the etiology and clinical impact of anemia, along with available therapeutic strategies, is essential during preoperative assessment and optimization
Iron studies (ferritin, TSAT, serum iron, TIBC)[37-40]	Serum ferritin- Reflects body iron stores. Low in true iron deficiency. Dysregulated iron status (deficiency or overload) correlates with increased post-transplant mortality. TSAT: Percentage of transferrin bound with iron. (< 16%-20%) strong indicator of iron deficiency. Serum iron: Circulating iron bound to transferrin. Decreased in IDA. Varies with inflammation; needs context with TSAT/TIBC. TIBC: Total iron-binding capacity of transferrin. Increases in absolute deficiency
Ferritin with CRP[41]	Serum ferritin to C-reactive protein (SF/CRP) ratio ≤ 6 serves as a straightforward and reliable marker of iron deficiency, even in patients with significant systemic inflammation or comorbid conditions
Reticulocyte index[42]	RPI based algorithm can be followed to treat the anemia
Vitamin B12 and folate levels[43]	Folate and vitamin B12 deficiencies were independently and strongly associated with preoperative anemia, together contributing to nearly one-third of the overall anemia burden. The frequent coexistence of multiple deficiencies, along with considerable variability across surgical populations, highlights the importance of adopting comprehensive but population-tailored diagnostic and supplementation approaches
Renal function tests[44]	Renal dysfunction both pre-existing and post-transplant directly impairs erythropoietin production, iron utilization, and red cell survival, thereby contributing to preoperative and postoperative anemia in OLT patients. The high incidence of post-OLT renal failure, particularly severe renal impairment requiring RRT, limits physiological tolerance to anemia and increases transfusion requirements. PBM strategies that identify renal dysfunction early enable optimization of anemia management (e.g., correction of iron deficiency, avoidance of unnecessary phlebotomy, and judicious transfusion), thereby reducing reliance on allogeneic blood products in a population already vulnerable to anemia
Hepcidin measurement[45,46]	Hepcidin, a key regulator of iron homeostasis synthesized in the liver, is dysregulated in cirrhosis, with elevated levels reflecting inflammation-mediated iron restriction and suppressed levels indicating true iron deficiency due to reduced hepatic synthetic capacity. Evidence demonstrating that low baseline hepcidin reliably identifies iron deficiency and correlates with iron absorption capacity despite inflammatory confounding, is therefore highly applicable to OLT candidates. Measurement of baseline hepcidin may allow differentiation between true iron deficiency and functional iron sequestration, enabling identification of patients likely to benefit from targeted oral or intravenous iron therapy while avoiding ineffective or potentially harmful empirical supplementation
Hypersplenism assessment (imaging + cytopenias)[47,48]	Identifying hypersplenism pretransplant is clinically important. Hypersplenism-related thrombocytopenia contributes to perceived bleeding risk and often prompts prophylactic transfusion, despite limited correlation between platelet count alone and bleeding in cirrhosis. Early recognition allows for individualized planning, including avoidance of unnecessary platelet transfusions, consideration of thrombopoietin receptor agonists in selected patients, and reliance on viscoelastic testing to guide intraoperative hemostatic therapy
Sarcopenia assessment (CT-based)[49,50]	Sarcopenia reflects chronic malnutrition, systemic inflammation, hormonal dysregulation, and reduced physical reserve factors that directly impair tolerance to anemia and surgical stress. Patients with sarcopenia have reduced cardiopulmonary and metabolic reserve, making them less able to compensate for perioperative blood loss or anemia and more likely to require transfusion click or tap here to enter text
Frailty assessment (Liver Frailty Index)[51]	Sarcopenia serves as a marker of frailty and diminished physiologic reserve, both of which are associated with higher postoperative morbidity, prolonged ICU stay, and mortality outcomes that are also independently linked to increased transfusion exposure
Predictive transfusion risk models, other predictors include CTP-A/hemoglobin concentration, INR, and total time of graft ischemia are preoperative variables associated with blood requirements during OLT and in the subsequent days[52-55]	Higher Child-Turcotte-Pugh class, lower hemoglobin concentration, elevated INR, and prolonged total graft ischemia time are linked to increased transfusion needs during surgery and in the early postoperative period. In addition, higher MELD scores, extended cold and warm ischemia times, prior abdominal surgery, and longer operative duration have been identified as independent predictors of intraoperative massive transfusion, commonly defined as the requirement for ten or more units of packed red blood cells. Lower platelet counts and increasing MELD scores particularly driven by elevated INR and bilirubin have also been correlated with greater blood component utilization during OLT, although the overall predictive accuracy of these models remains limited
Measurement of the hepatic venous pressure gradient (HVPG)[56]	Stratification of patients based on HVPG identifies distinct bleeding risk profiles, with lower risk observed in patients with HVPG values below 16 mmHg, substantially higher risk at values ≥ 16 mmHg, and a very high bleeding risk when HVPG reaches or exceeds 20 mmHg. Incorporating HVPG into the pretransplant anaesthetic assessment enables proactive, PBM-aligned perioperative planning click or tap here to enter text

Hb: Hemoglobin; PBM: Patient blood management; TSAT: Transferrin saturation; TIBC: Total iron-binding capacity; CRP: C-reactive protein; SF/CRP: Serum ferritin-to-C-reactive protein ratio; RPI: Reticulocyte production index; IDA: Iron deficiency anemia; OLT: Orthotopic liver transplantation; RRT: Renal replacement therapy; CT: Computed tomography; INR: International normalized ratio; MELD: Model for end-stage liver disease; CTP: Child-Turcotte-Pugh; ICU: Intensive care unit.

Anemia correction

Preoperative anemia is common in surgical patients and is independently associated with increased RBC transfusion, perioperative morbidity, and healthcare costs. Moderate-quality evidence suggests that combined recombinant human erythropoietin and iron therapy reduces the likelihood of perioperative RBC transfusion and increases preoperative Hb levels, particularly at higher doses. However, it does not consistently reduce the number of units transfused per patient or improve short-term clinical outcomes. Importantly, no significant increase in adverse events or short-term mortality has been demonstrated, but further adequately powered randomized trials are needed[57].

Structured preoperative anemia screening and treatment programs within PBM clinics have been shown to be cost-effective, significantly reducing transfusion requirements and overall hospital costs. Early identification of iron deficiency, using ferritin and transferrin saturation, allows timely intervention before anemia develops. While oral iron is inexpensive, its effectiveness is limited by poor absorption and gastrointestinal intolerance, particularly in inflammatory states. Intravenous iron provides more predictable Hb correction, bypasses hepcidin-mediated iron blockade, and is especially effective when used alongside erythropoiesis-stimulating agents. Newer intravenous iron formulations, such as ferric carboxymaltose, enable rapid, high-dose iron repletion with favorable safety profiles, supporting their role as a cornerstone of modern preoperative anemia management aimed at minimizing unnecessary transfusion and improving perioperative outcomes[58].

Optimize coagulation and minimize blood loss

In ESLD, both the number and function of platelets, as well as the hepatic synthesis of multiple coagulation factors, are altered. This includes reductions in procoagulant factors (such as factors II, V, VII, VIII, X, XI, XII, XIII, and fibrinogen) and anticoagulant proteins (including antithrombin, protein C, and protein S). These concurrent abnormalities create a fragile hemostatic balance, predisposing patients to both bleeding and thrombotic events. The simultaneous disruption of pro- and anticoagulant pathways underlies the complex and dynamic coagulation profile seen in these patients and necessitates careful, individualized clinical assessment. Factor VIII is a notable exception: Although partially produced outside the liver, its levels are markedly elevated in cirrhosis. This increase is largely driven by elevated von Willebrand factor (vWF), which binds and protects factor VIII from proteolytic degradation[59,60]. Elevated factor VIII promotes excess thrombin generation and is associated with an increased risk of venous thromboembolism[61]. Additionally, reduced protein C levels and resistance to thrombomodulin further shift the balance toward hypercoagulability, particularly in advanced (Child-Pugh C) cirrhosis[62-64].

Platelet abnormalities in liver disease

Under physiological conditions, platelet aggregation is initiated when endothelial injury exposes vWF and collagen, leading to platelet activation, shape change, and release of mediators such as adenosine diphosphate (ADP) and thromboxane A₂, which promote aggregation. Simultaneous activation of the coagulation cascade generates thrombin, which converts fibrinogen to fibrin, stabilizing the platelet plug with a fibrin mesh[65,66].

In ESLD, thrombocytopenia is common, primarily due to hypersplenism from portal hypertension, with platelet counts frequently ranging between 30-100 × 10⁹/L[67]. Beyond reduced platelet numbers, platelet function is impaired due to increased endothelial production of nitric oxide and prostacyclin, both potent inhibitors of platelet activation, further predisposing to bleeding[68-72].

Conversely, prothrombotic platelet-related changes also occur. Hepatic synthesis of ADAMTS13, a metalloproteinase responsible for cleaving ultra-large vWF multimers, is reduced in cirrhosis. This results in accumulation of ultra-large vWF, which enhances platelet adhesion and aggregation, partially compensating for platelet dysfunction[73]. However, elevated circulating vWF levels are associated with endothelial activation and poorer outcomes, including increased thrombotic risk, need for transjugular intrahepatic portosystemic shunt, LT, and reduced survival[74-76].

Fibrinogen quantity and quality

Fibrinogen, synthesized by hepatocytes, is cleaved by thrombin to form fibrin, which polymerizes and cross-links platelets to stabilize the clot[77]. In ESLD, fibrinogen levels may be reduced, especially in severe cirrhosis and acute liver failure, and fibrinogen function may be abnormal (dysfibrinogenemia)[78].

In mild to moderate cirrhosis, fibrinogen levels may be normal or elevated due to its role as an acute-phase reactant[79]. Reported median fibrinogen levels rise in Child-Pugh A and B cirrhosis but decline significantly in Child-Pugh C disease[80]. Dysfibrinogenemia in advanced disease is attributed to increased sialylation of the fibrinogen molecule, impairing fibrin polymerization and clot stability[81].

Fibrinolysis dysregulation

The final phase of hemostasis-fibrinolysis is also altered in liver disease. Plasmin-mediated fibrin degradation depends on conversion of plasminogen to plasmin by factor XIIa, tissue plasminogen activator (t-PA), and urokinase. Inhibition of fibrinolysis is mediated in part by thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by the thrombin–thrombomodulin complex[82,83].

TAFI levels are typically reduced in ESLD due to impaired hepatic synthesis, contributing to a tendency toward hyperfibrinolysis and bleeding[84]. However, studies using thromboelastography (TEG) in acute and decompensated liver disease have demonstrated preserved or even hypofibrinolytic states, possibly due to increased plasminogen activator inhibitor (PAI) levels and reduced plasminogen concentrations[85,86]. Thus, the clinical relevance of fibrinolytic abnormalities in cirrhosis remains variable and context dependent.

Overall hemostatic concept

Although cirrhosis results in concurrent reductions of both procoagulant and anticoagulant factors, this does not represent true normalization of hemostasis. Instead, patients exist in a fragile, “rebalanced” state that is highly susceptible to tipping toward either bleeding or thrombosis with even minor physiological stressors. These complex interactions limit the predictive value of conventional coagulation tests and underscore the dynamic nature of coagulation in liver disease[87].

Pathophysiology of hemostasis imbalance in LT

In summary, LT is characterized by a dynamic and continuous alteration of hemostatic mechanisms, with concurrent changes in both procoagulant and anticoagulant factors. These alterations affect both primary and secondary hemostasis, resulting in a fragile and evolving balance throughout the perioperative period. Primary hemostasis is characterized by thrombocytopenia and qualitative platelet dysfunction, accompanied by elevated plasma levels of vWF and reduced activity of ADAMTS-13.

Secondary hemostasis shows a simultaneous reduction in both procoagulant and anticoagulant factors, with the notable exception of factor VIII, which is typically increased. Plasma concentrations of fibrinolytic proteins are generally reduced, with the exception of t-PA and PAI-1, which are frequently elevated. Elevated vWF levels show a strong association with clinically significant portal hypertension in patients with compensated cirrhosis, suggesting that altered portal blood flow and shear stress are key determinants of vWF plasma concentrations in this population. All procoagulant and anticoagulant factors altered in liver disease are described in Figure 1.

Figure 1 Rebalanced hemostasis in end-stage liver disease. t-PA: Tissue plasminogen activator; TAFI: Thrombin-activatable fibrinolysis inhibitor; VWF: Von Willebrand factor; PAI: Plasminogen activator inhibitor.

Methods for coagulation assessment

Patients with ESLD exhibit a complex, rebalanced hemostatic state that predisposes them to both bleeding and thrombotic complications. Traditional coagulation tests, such as prothrombin time and international normalized ratio (INR) are frequently abnormal in this population, yet they were developed for monitoring anticoagulant therapy and do not reliably predict perioperative bleeding risk or transfusion requirements. Despite elevated INR values, cirrhotic patients remain at significant risk for venous thromboembolism, challenging the long-held concept of auto-anticoagulation. In the context of PBM pillar 2, which emphasizes minimizing blood loss and avoiding unnecessary transfusion, accurate and rapid assessment of coagulation particularly in the operating room is critical. Viscoelastic coagulation assays provide a dynamic, whole-blood evaluation of clot formation, strength, and fibrinolysis, offering superior guidance for goal-directed transfusion strategies during LT compared with conventional laboratory tests. Various methods of coagulation assessment are described in Table 4[88-96].

Table 4 Traditional and newer methods of coagulation assessment in liver disease and liver transplantation.

Assessment method	What It measures?	Key findings	Clinical utility	Major limitations	Ref.
Prothrombin time (PT)	Extrinsic and common pathway clotting factors	Prolonged due to reduced procoagulant factor synthesis	Historically used to assess bleeding risk	Does not account for reduced anticoagulants; poor bleeding predictor	[88,89]
International normalized ratio (INR)	Standardized PT (warfarin-based)	Elevated despite thrombotic risk	Not validated for bleeding risk	Misleading INR	[90-92]
Platelet count	Platelet quantity	Thrombocytopenia common but bleeding unpredictable	Baseline assessment	Does not reflect platelet function	[93]
aPTT	Intrinsic pathway (kaolin-based)	Often prolonged; kaolin-based activation	Screening test	Poor correlation with actual coagulation status	[94]
Fibrinogen (Clauss)	Functional fibrinogen level	May be low, normal, or high depending on disease stage	Guides cryoprecipitate use	Does not detect dysfibrinogenemia	[95]
D-dimer	Fibrin degradation	Often elevated regardless of bleeding	Marker of fibrinolysis	Poor specificity in cirrhosis	[89]
Static plasma-based testing	Traditional labs (combined)	Fail to predict bleeding vs thrombosis	Preoperative screening	Cannot reflect “rebalanced hemostasis”	[96]

aPTT: Activated partial thromboplastin time; D-dimer: Fibrin degradation product D-dimer; Clauss: Clauss method for fibrinogen measurement.

Point of care testing for coagulation abnormality

Amongst point-of-care modalities, viscoelastic tests such as TEG and rotational thromboelastometry (ROTEM^™) are most widely used during LT[97,98]. ROTEM^™ provides a dynamic assessment of clot development and stability in whole blood samples over time[99,100]. The simultaneous application of multiple ROTEM™ assays facilitates differentiation between distinct hemostatic defects, including impaired clot formation, platelet dysfunction, and hyperfibrinolysis[100].

By identifying the predominant mechanism underlying coagulopathy, ROTEM^™ enables individualized hemostatic management using coagulation factor concentrates, platelet transfusions, and antifibrinolytic agents, while reducing reliance on fresh frozen plasma and avoiding routine prophylactic antifibrinolytic administration. To support this targeted approach, ROTEM^™-guided treatment algorithms are shown in Figure 2.

Figure 2 Algorithm for rotational thromboelastometry guided transfusion. EXTEM: Extrinsic thromboelastometry; FIBTEM: Fibrinogen thromboelastometry; APTEM: Aprotinin thromboelastometry.

In addition to ROTEM^™, TEG^® is widely utilized during LT as a viscoelastic point-of-care modality for real-time assessment of global hemostasis[101,102]. TEG^® provides continuous information on clot initiation, propagation, maximal clot strength, and fibrinolysis using whole-blood samples, thereby reflecting the complex interaction between coagulation factors, platelets, fibrinogen, and fibrinolytic pathways[103]. Similar to ROTEM^™, TEG^® supports goal-directed hemostatic therapy by enabling early detection of hypocoagulability, hypercoagulability, and hyperfibrinolysis, and by guiding targeted administration of blood components and coagulation factor concentrates[104]. The application of TEG^® during LT has been associated with a reduction in ABT requirements and improved transfusion stewardship, although result interpretation remains operator-dependent and requires structured training and institution-specific algorithms[105,106]. Figure 3 provides a TEG based algorithm for the treatment of patients with abnormal tracing.

Figure 3 Algorithm for thromboelastography guided transfusion. FF-MA: Functional fibrinogen maximum amplitude; TEG: Thromboelastography; PCC: Prothrombin concentrate, FFP: Fresh frozen plasma.

NEWER ASSESSMENT METHODS

Thrombin generation assay

Thrombin generation assay (TGA) provides a global assessment of hemostatic balance by quantifying endogenous thrombin potential and thrombin kinetics. In chronic liver disease and cirrhosis, TGA has demonstrated preserved or even increased thrombin generation despite prolonged conventional coagulation tests, thereby elucidating the concept of rebalanced hemostasis[107]. This characteristic makes TGA a valuable research tool for understanding coagulation mechanisms in patients undergoing orthotopic LT (OLT), in whom both bleeding and thrombotic complications coexist. Although TGA has shown utility in hemorrhagic disorders, anticoagulant monitoring, and venous thromboembolism risk stratification in other clinical settings, its role in OLT remains investigational. Future studies integrating TGA parameters with clinically relevant intraoperative and postoperative endpoints, such as transfusion requirements, graft thrombosis, and bleeding complications, are required before routine perioperative application can be recommended.

Modified calibrated automated thrombography

In patients undergoing OLT, platelet number and function are frequently impaired due to thrombocytopenia, qualitative platelet defects, and altered platelet–endothelium interactions. Conventional calibrated automated thrombography (CAT) performed in platelet-free plasma fails to capture platelet-dependent contributions to thrombin generation that are clinically relevant in this population. Modified CAT approaches using platelet-rich plasma with controlled platelet activation or aggregation provide mechanistic insight into platelet-driven thrombin kinetics and may better reflect the perioperative hemostatic balance in OLT[108].

Experimental models incorporating platelet activation by weak (ADP) or strong (collagen) agonists demonstrate that platelet aggregation accelerates thrombin generation primarily by shortening lag time and time to peak, rather than increasing endogenous thrombin potential. These findings suggest that platelet granule release and platelet-derived extracellular vesicles significantly influence thrombin kinetics independent of total thrombin output. In the context of OLT, where thrombocytopenia, platelet dysfunction, and endothelial activation coexist, such platelet-modified CAT assays may help differentiate bleeding due to impaired platelet activation from preserved or excessive thrombin generation masked by abnormal conventional coagulation tests.

Although these approaches remain research tools, platelet-augmented CAT may be valuable for phenotyping coagulation risk in selected OLT patients, particularly those with disproportionate bleeding despite near-normal viscoelastic parameters or unexplained thrombotic events in the postoperative period. Integration of platelet-modified CAT with clinical outcomes such as transfusion requirements, portal vein thrombosis, and early graft dysfunction warrants further investigation before routine clinical implementation.

Clot waveform analysis

Clot waveform analysis (CWA), offers dynamic quantitative parameters beyond conventional tests and has been shown to correlate with cirrhosis severity and composite prognostic scores in patients with chronic liver disease (e.g., decreased CWA velocity and acceleration parameters in advanced cirrhosis)[109]. CWA extends routine PT/aPTT by evaluating clot formation kinetics, and although clinical evidence in OLT candidates is still emerging, case reports demonstrate its potential utility in perioperative hemostatic monitoring in complex transplantation settings, such as patients requiring specialized coagulation management during transplantation[110]. Broader reviews of CWA methods underscore the range of its modified assays for assessing hypercoagulability and fibrinolysis, supporting further investigation of its role in advanced liver disease and transplant populations[111].

A comprehensive assessment of cardiopulmonary reserve and end-organ function is a foundational element of PBM in patients scheduled for OLT. Evaluation of cardiac performance, pulmonary function, renal status, and complications related to portal hypertension identifies patients with limited physiological reserve who are at increased risk of perioperative instability, bleeding, and transfusion. Conditions such as cirrhotic cardiomyopathy, porto-pulmonary hypertension, hepatopulmonary syndrome, and renal dysfunction adversely affect oxygen delivery and tolerance to anemia during transplantation. Early identification of these factors allows targeted preoperative optimization and informed perioperative planning, thereby reducing unnecessary transfusion and improving outcomes[112-115].

Optimization of oxygen delivery is a central PBM strategy in OLT candidates, particularly in the context of chronic anemia and impaired cardiopulmonary reserve. Nutritional optimization, management of sarcopenia, respiratory physiotherapy, and optimization of cardiac output improve global oxygen delivery and enhance tolerance to anemia during the dissection, anhepatic, and reperfusion phases of transplantation. Rather than correcting Hg values in isolation, PBM emphasizes improving the determinants of oxygen delivery, cardiac output, arterial oxygenation, and Hb functionality, thereby reducing reliance on allogeneic blood products. This physiology-based approach is especially relevant in LT, where perioperative transfusion has been independently associated with increased morbidity and poorer graft outcomes.

Education of the multidisciplinary transplant team regarding restrictive transfusion thresholds is essential for effective PBM implementation in OLT. Traditional reliance on liberal transfusion strategies driven by abnormal laboratory values, particularly the INR, has been shown to poorly predict bleeding risk in cirrhosis. Restrictive RBC transfusion strategies (e.g., transfusion thresholds around Hb 7-8 g/dL in hemodynamically stable patients) are widely endorsed in major surgery and critical care, and are associated with reduced exposure to allogeneic blood products without increased morbidity[116]. Although randomized trials specific to OLT are limited, available evidence supports the safety of restrictive approaches when transfusion decisions are guided by clinical context and dynamic coagulation assessment rather than static plasma-based tests alone.

INTRA-OPERATIVE MANAGEMENT

Low CVP, commonly targeted at < 5 mmHg, is widely used during liver resection and OLT to reduce surgical blood loss and transfusion requirements. This can be achieved through controlled volume restriction, vasodilation, diuresis, neuromuscular blockade, and ventilatory optimization. In living donor hepatectomy, prophylactic phlebotomy has been shown to lower CVP without adversely affecting postoperative outcomes. Advances in surgical technique and coagulation management have further contributed to reduced transfusion rates. However, excessively low or prolonged intraoperative CVP has been associated with complications such as air embolism, tissue hypoperfusion, renal dysfunction, and increased short-term mortality, underscoring the need for a balanced, phase-specific low-CVP strategy[117-119].

Cell saver systems/cell salvage equipment are used for intra-operative auto transfusion. The commonly available ICS systems used worldwide, including in high–blood-loss surgeries such as OLT, include the Cell Saver Elite/Elite⁺ and Cell Saver 5/5⁺ (Haemonetics), AutoLog IQ (Medtronic), XTRA Autotransfusion System (LivaNova/Sorin Group), C.A.T.S^® Cell Salvage System (Fresenius Kabi), and newer platforms such as the same^™ autotransfusion system by i-SEP, which is designed to recover red cells with improved cellular quality. These devices are widely integrated into perioperative PBM programs and are routinely employed in cardiac, vascular, trauma, and liver transplant surgery to reduce ABT requirements and improve perioperative outcomes[120].

The ICS process comprises three stages: Collection, processing (separation and washing), and reinfusion. Reinfusion should occur under standard transfusion monitoring, without pressure infusion, and with appropriate labelling to prevent errors. Additional filtration (e.g., leukocyte depletion filters) may be used when there is concern about bacterial contamination or malignancy, although these can reduce infusion rates and are associated with reinfusion-related hypotension.

During surgery, shed blood is aspirated from the operative field or recovered from blood-soaked swabs, anticoagulated, filtered, and processed using centrifugation. Red cells are separated based on density, washed with isotonic saline, and reinfused as a high-hematocrit suspension (approximately 60%). Plasma, free Hb, anticoagulant, platelets, leukocytes, clotting factors, and contaminants are discarded. Careful suction techniques, appropriate suction pressures, and the use of suitable anticoagulants minimize mechanical and osmotic red cell injury[121].

ICS reduces reliance on allogeneic transfusion, supports restrictive transfusion strategies, and provides effective intravascular volume replacement with preserved oncotic properties. It is particularly valuable in patients with anticipated high blood loss, rare blood groups, multiple antibodies, or those declining donor transfusion for personal or religious reasons.

ANH is an autologous blood conservation technique introduced in the 1970s, initially in cardiac surgery, and now applied to a wide range of high-blood-loss procedures[122]. The principle involves withdrawing the patient’s own blood immediately after induction of anesthesia and simultaneously replacing the volume with crystalloids and/or colloids to maintain normovolemia. Typically, one to three units of whole blood are collected and stored in the operating room, then retransfused during surgery or within 6-8 hours postoperatively. ANH is unique among BCS in that it preserves whole blood, containing functional red cells, platelets, and coagulation factors, without evidence of hemolysis, coagulopathy, fibrinolysis, or immunologic activation[123].

The primary goal of ANH is to reduce intraoperative red cell loss by lowering circulating hematocrit while maintaining adequate intravascular volume, thereby decreasing the need for allogeneic transfusion. Additional benefits include avoidance of transfusion-related reactions and infections, preservation of platelet and coagulation factor activity, improved blood rheology, and potentially enhanced tissue oxygen delivery. Multiple meta-analyses and clinical studies across cardiac, orthopedic, oncologic, and complex surgical populations have demonstrated a significant reduction in ABT when ANH is used[124]. However, ANH requires careful patient selection and monitoring and is generally unsuitable for patients with pre-existing anemia, significant cardiac dysfunction, renal failure with oliguria, or limited physiological reserve. When applied appropriately, ANH remains a simple, low-cost, and effective component of modern PBM strategies[125].

PHARMACOLOGICAL THERAPY TO REDUCE BLOOD TRANSFUSION IN LT

A range of pharmacologic interventions is available for the prevention and management of bleeding during liver surgery. However, these agents should be used as adjuncts rather than standalone measures for blood loss reduction. Broadly, they can be classified into three main groups: Topical hemostatic agents, antifibrinolytic medications, and procoagulant drugs. Commonly used antifibrinolytic drugs are tranexamic acid (TXA), aprotinin, and nafamostat mesylate, have shown encouraging results, particularly in decreasing intraoperative blood loss and transfusion requirements[126-128]. However, the current evidence is limited by a small number of randomized controlled trials, small sample sizes, and a high risk of both type I and type II errors, which restricts the strength of conclusions that can be drawn. Safety concerns have further tempered enthusiasm for routine use; aprotinin was temporarily withdrawn due to associations with thrombosis, renal dysfunction, and increased mortality, while the thromboembolic risk of TXA remains uncertain[129]. These issues likely contribute to the paucity of high-quality trials and cautious clinical adoption. Although available data suggest benefit, especially in high-risk situations such as repeat or parenchyma-sparing liver resections, further well-designed, adequately powered randomized trials with low risk of bias are needed. Future studies should assess clinically relevant outcomes, including perioperative mortality, and evaluate the combined impact of pharmacological and non-pharmacological BCS.

Common procoagulants are cryoprecipitate, prothrombin complex concentrates (PCC), vitamin K, and fibrinogen concentrate.

Topical hemostatic agent therapies

Topically applied hemostatic agents are broadly classified into active agents, mechanical hemostats, synthetic or hemisynthetic sealants, and external hemostatic dressings. Active topical hemostats contain components such as fibrinogen and thrombin and exert their effect by directly activating the coagulation cascade, leading to fibrin clot formation. As their mechanism does not rely solely on the patient’s endogenous hemostatic system, these agents are particularly beneficial in individuals. Tables 5, 6 and 7 detail various topical agents available for hemostasis[130-162].

Table 5 Topical and mechanical hemostatic agents.

Sub-class	Works on	Feature	Limitation	Ref.
Fibrin-based liquid adhesives: Tisseel, evicel	Broad oozing surfaces, vascular anastomoses, coagulopathic patients	Provide fibrinogen + thrombin: Fibrin clot formation	Air embolism with spray, intravascular thrombosis, viral transmission risk	[130,131]
Fibrin patches/sponges: TachoSil, evarrest, fibrin pad	Severe bleeding, liver resection, cardiac surgery	Adhesive + mechanical scaffold prevents streaming effect	Severe bleeding, liver resection, cardiac surgery	[132-135]
Thrombin-only agents: Human thrombin, bovine thrombin, recombinant thrombin	Adjunct to surgical hemostasis	Converts fibrinogen to fibrin	Immunogenicity, thrombosis, viral risk (plasma-derived)	[13,137]
Flowable gelatin and thrombin: Floseal, surgiflo	Rapid hemostasis across specialties	Mechanical matrix + active clot formation	Swelling, infection, compression injury	[138-141]

Table 6 Topical synthetic hemostatic agents.

Sub-class	Works on	Feature	Limitation	Ref.
Cyanoacrylates (Octyl-2, Butyl-2)	Moisture-induced polymerization forming tissue adhesion	Rapid sealant, waterproof, sutureless closure; used for skin wounds and variceal embolization	Embolic risk if intravascular; toxic degradation products; unsuitable for mucosa, joints, avulsed tissue, or vascular anastomoses	[142-144]
Microporous polysaccharide hemospheres	Absorb fluid to concentrate platelets and clotting proteins	Accelerates endogenous clotting; reduces time to hemostasis	Ineffective in severe coagulopathy; limited efficacy in high-pressure bleeding	[145]
PEG hydrogel (CoSeal)	Cross-linked hydrogel sealing tissue planes	Sealant and anti-adhesion barrier; non-exothermic, low inflammation; reduces pericardial adhesions	Swelling may compress adjacent structures; poor adhesion to renal parenchyma	[146]
Glutaraldehyde cross-linked albumin (BioGlue)	Protein cross-linking forming rigid adhesive scaffold	Strong adhesion to tissue and synthetic grafts; useful in vascular/cardiac surgery	Tissue toxicity, stenosis risk; avoided in young patients	[147-149]
Synthetic hemostatic nanomolecules	Cationic interaction enhances platelet aggregation	Rapid hemostasis in experimental liver and trauma models	Predominantly preclinical; limited human safety data	[149-151]

Table 7 External hemostatic dressings.

Sub-class	Works by	Feature	Limitation	Ref.
Fibrinogen-based dressings	Direct fibrin clot formation independent of host coagulation	Effective even in hypothermia and coagulopathy; useful for open wounds	Limited availability; biological product considerations	[152]
Zeolite-based dressings (QuikClot®, ACS)	Absorb water to concentrate clotting factors and cells	Rapid hemostasis in trauma; effective in junctional hemorrhage	Exothermic reaction; thermal injury, difficult removal, ineffective in arterial bleeding	[153-155]
Clay-based dressings	Surface charge–mediated activation of intrinsic pathway	Thermally stable; high surface area, ion exchange capability	Variable swelling, material-specific inflammatory risk	[156]
Kaolin-based dressings (QuikClot Combat Gauze®)	Contact activation of intrinsic coagulation (factors XII, XI)	No exothermic injury; strong clinical evidence; standard military use	Limited efficacy in massive arterial bleeding	[157]
Smectite-based dressings (e.g., WoundStat®)	Water absorption and intrinsic pathway activation	High absorption, swelling, and viscosity; effective hemostasis	Severe inflammation, tissue necrosis; difficult removal; withdrawn from use	[158]
Chitin/chitosan-based dressings	Electrostatic interaction with erythrocytes and platelets (coagulation-independent)	Effective in coagulopathy, antimicrobial, biocompatible	Expensive; shellfish allergy concern; requires training for optimal use	[159,160]
Polyelectrolyte complexes (chitosan-based PECs)	Electrostatic polymer interactions accelerating coagulation	Rapid clotting; antimicrobial activity; good tissue compatibility	Largely experimental; limited human clinical data	[161]
Chitosan bandages (HemCon®)	Mechanical sealing and tissue adhesion	Proven antimicrobial properties	Requires hands-on training, adhesion may be difficult in emergencies	[162]

INTRAOPERATIVE TECHNIQUES AND ADJUNCTS TO REDUCE BLOOD LOSS

Parenchymal transection devices

(1) Ultrasonic harmonic scalpel, reduces blood loss and transfusion compared to the clamp crush technique in open and laparoscopic liver resections[163]; (2) Water-jet dissector, a selective parenchymal dissection with vessel preservation, is associated with reduced blood loss[164]; and (3) Cavitron ultrasonic surgical aspirator is widely used to facilitate parenchymal dissection while preserving vascular structures useful in complex resections[165].

Advanced hemostatic energy devices

Bipolar vessel-sealing devices (LigaSure^®, ENSEAL^®: Reliable vessel sealing up to 7 mm with reduced bleeding and operative time[166]. Advanced energy-based tissue sealers have played a pivotal role in the expansion of minimally invasive surgery by enhancing operative efficiency, shortening procedure time, and reducing complication rates. LigaSure vessel-sealing systems are widely regarded as a benchmark in laparoscopic surgery, offering fast, reliable, and user-friendly device-controlled sealing, with proven efficacy in sealing vessels up to 7 mm in diameter[167]. ENSEAL represents another established advanced bipolar sealing platform and has demonstrated comparable performance to LigaSure in previous evaluations. Earlier generations of both devices exhibited similarly high seal integrity and acceptable thermal spread while outperforming many alternative technologies.

THUNDERBEAT^®: Thunderbeat is a hybrid surgical energy device that combines ultrasonic energy and advanced bipolar energy in a single instrument.

Radiofrequency ablation-assisted transection: Pai et al[168] were among the first to introduce radiofrequency ablation (RFA) as an adjunct for hepatic parenchymal transection, demonstrating that a single-probe RFA technique could effectively reduce intraoperative blood loss. In their approach, a metallic probe was inserted vertically into the liver tissue to achieve coagulation. In contrast, subsequent techniques have allowed more flexible probe positioning, enabling both horizontal and perpendicular application within the parenchyma. An alternative strategy is the inline RFA method, in which a defined zone of coagulation is generated between electrodes of alternating polarity, producing a controlled ablation plane that facilitates safer and more blood-sparing liver transection[169].

Microwave ablation: Rapid, larger coagulation zones for pre-emptive sealing of transection planes[170].

Temporary portocaval shunts

Temporary portocaval shunts (PCS) are employed to decompress the portal venous system, thereby reducing portal hypertension and minimizing blood loss during recipient hepatectomy. In addition, PCS contributes to improved hemodynamic stability, attenuation of the inflammatory stress response, and reduction of endotoxemia during the anhepatic phase[171].

Figueras et al[172] demonstrated that the use of PCS was associated with better hemodynamic parameters and reduced transfusion requirements. Similar benefits were reported by Ghinolfi et al[173] and Margarit et al[174]. In contrast, Pietersen et al[175] found no significant difference in clinical outcomes with PCS use. In a randomized clinical trial, Yi et al[176] reported a significant reduction in RBC, platelet, and plasma transfusion requirements in patients undergoing PCS. Furthermore, a meta-analysis by Pratschke et al[177], including six studies, showed a significant reduction in blood transfusion requirements associated with PCS. More recently, Mataruco et al[178] also demonstrated a significant decrease in RBC transfusion in patients receiving temporary PCS. Overall, the available evidence suggests that PCS is associated with a meaningful reduction in perioperative transfusion requirements, although heterogeneity exists among studies.

Various types of temporary portosystemic shunts have been described in the literature. These include portocaval anastomosis, right portocaval anastomosis, iliac venous conduit interposition, portal vein cannulation with shunting to the inferior vena cava, portoumbilical anastomosis, porto-femoral shunt, meso-saphenous shunt (via inferior mesenteric vein cannulation), and rex-saphenous shunt.

POST-OPERATIVE PHASE OPTIMIZATION

Adherence to PBM principles, such as minimizing unnecessary routine blood sampling and adopting a targeted, indication-based approach to investigations, can substantially reduce avoidable blood loss. Additionally, optimization of oxygen delivery and cardiac output in the intensive care unit (ICU) setting is crucial to mitigate the physiological consequences of anemia and reduce reliance on transfusion[179]. Emerging evidence from ongoing clinical trials indicates that post-operative intravenous iron therapy may play a beneficial role in the treatment of peri-operative anemia and in accelerating hematological recovery following surgery[180-182]. The ICU plays a pivotal role in post-operative monitoring and organ support following major surgery; however, this environment is also associated with PBM-relevant challenges. Iatrogenic anemia is a well-recognized complication in critically ill patients, largely driven by frequent diagnostic phlebotomy. Evidence suggests that ICU patients lose an average of 52.4 mL of blood per day due to laboratory testing alone[183]. In the post-operative period, PBM strategies emphasize the importance of individualized, patient-centered care. Post-operative anemia should be actively identified and managed, with transfusion thresholds tailored to the patient’s physiological status and comorbid conditions. Restrictive transfusion strategies should be consistently maintained across the entire peri-operative pathway. In this context, the traditional practice of routine two-unit RBC transfusions in non-bleeding patients must be reconsidered. Current PBM recommendations advocate single-unit RBC transfusions in hemodynamically stable patients without active bleeding, as this approach enhances patient safety while also offering economic advantages. Following each single-unit transfusion, a structured clinical reassessment, including repeat Hb measurement, should be performed, with further transfusion administered only if clinically indicated. In parallel, optimization of erythropoiesis through adequate nutrition and targeted iron and vitamin supplementation is essential to support bone marrow recovery and reduce transfusion dependency. Sepsis contributes to post-operative anemia and increased transfusion requirements; therefore, prompt identification and early source control are essential to reduce the need for blood transfusion. Early initiation of enteral nutrition facilitates faster hematologic recovery and supports optimal graft function. Similarly, early mobilization promotes physiological stability and accelerates overall recovery. The use of viscoelastic testing-guided transfusion strategies (TEG/ROTEM) allows targeted correction of coagulopathy, such as fibrinogen replacement, platelet transfusion, or PCC when appropriate, while avoiding empiric blood product use. Collectively, these post-operative strategies contribute to reduced transfusion requirements and improved clinical outcomes following LT.

FUTURE PERSPECTIVE

The future of BCS in LT is focused on a patient-specific and evidence-based approach. Wider implementation of PBM protocols and viscoelastic testing-guided transfusion will allow targeted correction of coagulation abnormalities and reduce unnecessary transfusions. Advances in surgical techniques, energy devices, and pharmacologic agents are expected to further minimize blood loss. The increasing use of viscoelastic point-of-care testing (TEG/ROTEM) with algorithm-driven decision-making will enable real-time, targeted correction of coagulation abnormalities, minimizing empiric transfusion and thrombotic complications. Newer tests like TGA, platelet function and microfluidic assays, fibrinolysis profiling, endothelial and biomarker-based tests can help in better targeted transfusion. Integration of artificial intelligence and machine-learning models may further enhance the prediction of bleeding risk and guide transfusion strategies across the perioperative continuum.

CONCLUSION

LT is among the most complex surgical procedures, with perioperative blood loss and transfusion exposure remaining critical determinants of patient and graft outcomes despite major advances in surgical technique, anesthesia, and postoperative care. The unique, fragile “rebalanced” hemostatic state of ESLD renders traditional laboratory-driven, prophylactic transfusion practices both imprecise and potentially harmful. In this context, PBM provides a coherent, evidence-based framework to rationalize transfusion practice and optimize outcomes across the transplant continuum.

This review highlights that effective blood conservation in LT must be phase-integrated and multidisciplinary, addressing red cell mass optimization, minimization of blood loss, and enhancement of anemia tolerance. Early identification and treatment of preoperative anemia using uniform Hb thresholds, comprehensive iron and nutritional assessment, and selective use of intravenous iron and erythropoiesis-stimulating agents, reduces transfusion dependence and improves physiological reserve. Recognition of contributory factors such as renal dysfunction, hypersplenism, sarcopenia, frailty, and portal hypertension enables individualized risk stratification and targeted optimization.

Intraoperatively, refined surgical techniques, low-CVP anesthesia, autologous BCS, judicious pharmacologic adjuncts, and goal-directed hemostatic therapy guided by viscoelastic testing collectively minimize blood loss and unnecessary component therapy. Postoperatively, restrictive transfusion thresholds, avoidance of empiric correction of abnormal coagulation tests, and continued physiological optimization further limit transfusion-related harm.

Collectively, contemporary evidence supports a shift from laboratory-triggered transfusion toward physiology- and outcome-driven PBM strategies in LT. Adoption of structured PBM pathways has the potential to reduce transfusion exposure, preserve scarce blood resources, and improve both short- and long-term transplant outcomes. Future research should focus on refining risk prediction, integrating emerging coagulation assays, and validating transplant-specific PBM algorithms through high-quality prospective studies.