The Coagulopathy of Liver Disease: Bleeding vs. Clotting - A Critical Care Perspective

Dr Neeraj Manikath , claude.ai

Abstract

Background: Liver disease presents a unique hemostatic challenge, with patients exhibiting a paradoxical predisposition to both bleeding and thrombotic complications. The traditional coagulation cascade model inadequately explains this complex pathophysiology, leading to suboptimal management decisions in critical care settings.

Objective: To provide a comprehensive review of the rebalanced hemostasis theory in liver disease, emphasizing practical management strategies for the dual bleeding-thrombotic phenotype commonly encountered in critically ill patients.

Methods: Systematic review of current literature on liver-associated coagulopathy, with particular focus on viscoelastic testing applications and evidence-based management strategies.

Results: Modern understanding reveals that liver disease causes proportional reductions in both pro- and anti-coagulant factors, resulting in a "rebalanced" but fragile hemostatic system. Traditional tests (PT/INR) inadequately assess this balance, while viscoelastic testing provides superior guidance for clinical management.

Conclusions: A paradigm shift from routine prophylactic correction of abnormal conventional coagulation tests to targeted, indication-specific interventions based on comprehensive hemostatic assessment is essential for optimal patient outcomes.

Keywords: liver disease, coagulopathy, hemostasis, viscoelastic testing, thrombosis, bleeding

Introduction

The clinical scenario is all too familiar: a cirrhotic patient presents with gastrointestinal bleeding and an INR of 2.5, yet imaging reveals concurrent portal vein thrombosis. This apparent contradiction exemplifies the complex hemostatic dysfunction in liver disease—a condition that defies traditional coagulation paradigms and challenges even experienced intensivists.

For decades, the elevated INR in liver disease was interpreted through the lens of a "bleeding diathesis," prompting aggressive correction with fresh frozen plasma (FFP) and other blood products. However, accumulating evidence demonstrates that patients with liver disease face equal or greater risks of thrombotic complications, fundamentally challenging our therapeutic approach.

This review examines the contemporary understanding of liver-associated coagulopathy, emphasizing the critical care management of patients who simultaneously face bleeding and clotting risks—a clinical conundrum that demands nuanced, evidence-based decision-making.

Pathophysiology: The Rebalanced Hemostasis Theory

Traditional vs. Modern Understanding

The liver synthesizes virtually all coagulation factors except factor VIII and von Willebrand factor, along with key anticoagulant proteins including protein C, protein S, and antithrombin. Traditional teaching focused on the deficiency of pro-coagulant factors, interpreting prolonged PT/INR as indicative of bleeding risk.

The paradigm-shifting concept of "rebalanced hemostasis" was first articulated by Tripodi and Mannucci in 2007¹. This theory posits that liver disease causes proportional reductions in both pro- and anti-coagulant factors, resulting in a new hemostatic equilibrium rather than a simple bleeding tendency.

Pearl 1: The Hemostatic Balance Sheet

Think of liver disease as affecting both sides of the coagulation equation equally—it's not hemorrhagic by default; it's rebalanced but precarious.

Molecular Mechanisms

Pro-coagulant Factor Deficiencies:

Factors II, V, VII, IX, X, XI (synthesized exclusively by hepatocytes)
Fibrinogen (typically preserved until advanced disease)
Factor XIII (often overlooked but crucial for clot stability)

Anti-coagulant Protein Deficiencies:

Protein C (half-life 6-8 hours—falls early)
Protein S (both free and bound fractions affected)
Antithrombin (correlates closely with albumin synthesis)
Heparin cofactor II

Additional Complexities:

Elevated factor VIII (acute phase reactant, not liver-synthesized)
Reduced ADAMTS13 activity (acquired thrombotic thrombocytopenic purpura-like picture)
Platelet dysfunction despite often normal or elevated counts
Increased von Willebrand factor multimers

Hack 1: The "Factor VIII Paradox"

In liver disease, factor VIII levels are often elevated (normal synthesis + reduced clearance), while other factors are low. This creates a "hypercoagulable" factor VIII to other factor ratio—one reason why these patients can still clot despite abnormal PT/INR.

Diagnostic Challenges: Why Conventional Tests Fail

Limitations of Standard Coagulation Tests

PT/INR Limitations:

Reflects only 3-5% of total thrombin generation
Insensitive to anticoagulant protein deficiencies
Performed in platelet-poor plasma (ignores cellular interactions)
No assessment of clot stability or fibrinolysis

APTT Limitations:

Similar mechanistic limitations to PT/INR
Variable sensitivity to factor deficiencies
Poor correlation with bleeding risk in liver disease

Oyster 1: The INR Misconception

Many intensivists believe INR >1.5 mandates FFP before procedures. However, studies show no correlation between INR and bleeding risk in liver disease for most procedures. The INR was designed for warfarin monitoring, not liver disease assessment.

Platelet Count and Function

Thrombocytopenia in liver disease results from:

Portal hypertension and hypersplenism
Reduced thrombopoietin synthesis
Direct bone marrow suppression (alcohol, hepatitis C)

However, elevated thrombopoietin levels often maintain adequate platelet production, and larger, more active platelets may compensate for reduced numbers².

Pearl 2: The Platelet Paradox

Don't be fooled by low platelet counts. In liver disease, remaining platelets are often hyperactive, and thrombopoietin levels may be elevated, maintaining reasonable hemostatic function until counts drop below 50,000.

Viscoelastic Testing: The Game Changer

TEG/ROTEM Principles

Viscoelastic testing measures the entire process of clot formation, strength, and dissolution in whole blood, providing a comprehensive hemostatic assessment unavailable through conventional testing.

Key Parameters:

R-time/CT (Clotting Time): Time to initial clot formation
K-time/CFT (Clot Formation Time): Speed of clot development
α-angle: Rate of clot strengthening
MA/MCF (Maximum Amplitude/Clot Firmness): Ultimate clot strength
LY30/ML (Lysis): Percentage of clot dissolved at 30 minutes

Clinical Applications in Liver Disease

Bleeding Risk Assessment:

MA/MCF <40mm strongly predicts bleeding risk
Normal MA/MCF despite abnormal PT/INR suggests adequate hemostasis
LY30 >15% indicates hyperfibrinolysis requiring antifibrinolytic therapy

Thrombosis Risk Evaluation:

Shortened R-time/CT suggests hypercoagulability
Elevated MA/MCF indicates increased clot strength
Reduced fibrinolysis (LY30 <0.8%) predicts thrombotic risk

Hack 2: The TEG/ROTEM Sweet Spot

In liver disease, aim for MA/MCF values between 40-60mm. Below 40mm increases bleeding risk; above 60mm increases thrombotic risk. This "Goldilocks zone" guides both bleeding and thrombosis management.

Clinical Scenarios and Management Strategies

Scenario 1: The Bleeding Cirrhotic Patient

Case Presentation: A 55-year-old man with Child-Pugh Class B cirrhosis presents with hematemesis. Laboratory values: INR 2.3, platelet count 45,000/μL, hemoglobin 7.2 g/dL.

Traditional Approach:

Automatic FFP transfusion for INR >1.5
Platelet transfusion for count <50,000
Aggressive volume resuscitation

Evidence-Based Approach:

Perform TEG/ROTEM if available before reflexive transfusions
Target-specific therapy:
- FFP only if MA/MCF <40mm or active bleeding continues
- Platelets if severe dysfunction noted on viscoelastic testing
- Consider fibrinogen concentrate if levels <100 mg/dL
Avoid over-transfusion (increases portal pressure and rebleeding risk)

Pearl 3: The FFP Futility

Multiple studies show FFP rarely normalizes INR in liver disease and may worsen outcomes by increasing portal pressure. Transfuse for function, not numbers.

Scenario 2: The Thrombotic Risk Patient

Case Presentation: Same patient develops portal vein thrombosis during hospitalization. Should anticoagulation be initiated despite recent GI bleeding?

Management Principles:

Risk Stratification:
- Acute vs. chronic thrombosis
- Extent of thrombosis
- Bleeding site control status
Anticoagulation Considerations:
- Low molecular weight heparin preferred over unfractionated heparin
- Start low, go slow dosing strategy
- Monitor with anti-Xa levels rather than APTT
- Consider direct oral anticoagulants in stable patients (growing evidence base)

Hack 3: The Anticoagulation Algorithm

For liver disease patients requiring anticoagulation: Start with prophylactic LMWH doses, advance to therapeutic based on repeat imaging and bleeding assessment. TEG/ROTEM can guide this transition by showing when hemostatic balance tips toward thrombosis.

Scenario 3: Pre-Procedure Management

The Challenge: A cirrhotic patient requires paracentesis. INR is 1.8, platelets 60,000/μL. Standard guidelines suggest correction, but is it necessary?

Evidence-Based Approach:

Risk Assessment:
- Large-volume paracentesis: Generally safe without correction
- Liver biopsy: Consider TEG/ROTEM guidance
- Major surgery: Individualized assessment essential
Selective Correction:
- Correct only if viscoelastic testing shows severe dysfunction
- Use specific factor concentrates when possible
- Monitor post-procedure for both bleeding and thrombotic complications

Oyster 2: The Paracentesis Myth

Studies consistently show that routine correction of "abnormal" coagulation parameters before paracentesis does not reduce bleeding complications and may increase costs and complications unnecessarily.

Advanced Management Strategies

Factor Concentrate Therapy

Prothrombin Complex Concentrate (PCC):

Contains factors II, VII, IX, X plus proteins C and S
More physiologic than FFP
Lower volume load
Faster correction of coagulopathy

Fibrinogen Concentrate:

Direct replacement of deficient fibrinogen
Avoid cryoprecipitate when possible (infectious risk)
Target levels >150 mg/dL in bleeding patients

Factor XIII:

Often overlooked but crucial for clot stability
Consider in refractory bleeding with normal other parameters

Pearl 4: The Concentrate Advantage

Factor concentrates provide targeted therapy without the volume overload and variable factor content of FFP. They're particularly valuable in the critically ill patient who cannot tolerate additional fluid.

Antifibrinolytic Therapy

Tranexamic Acid:

Highly effective in liver disease-associated hyperfibrinolysis
Use when TEG/ROTEM shows LY30 >15%
Lower doses (10-15 mg/kg) often sufficient

ε-Aminocaproic Acid:

Alternative when tranexamic acid unavailable
Longer half-life, higher thrombotic risk

Artificial Liver Support

Molecular Adsorbent Recirculating System (MARS):

Removes protein-bound toxins
May improve coagulation function
Limited availability, high cost

Fractionated Plasma Separation and Adsorption (FPSA):

Removes inflammatory mediators and toxins
Potential coagulation benefits
Investigational in most centers

Special Populations and Scenarios

Acute-on-Chronic Liver Failure (ACLF)

ACLF patients exhibit particularly complex hemostatic dysfunction:

Systemic inflammation shifts balance toward hypercoagulability
Multiple organ failure complicates assessment
Higher thrombotic risk despite bleeding tendency

Management Considerations:

More aggressive anticoagulation may be warranted
TEG/ROTEM absolutely essential for management
Consider thromboprophylaxis even with "abnormal" conventional parameters

Hack 4: The ACLF Exception

In ACLF, systemic inflammation often creates a hypercoagulable state despite abnormal PT/INR. These patients may need therapeutic anticoagulation even with INR >2.0—let TEG/ROTEM be your guide.

Post-Transplant Coagulopathy

Immediate Post-Operative Period:

Primary non-function: Severe bleeding risk
Good early function: Rapid normalization expected
Hepatic artery thrombosis: Requires immediate anticoagulation

Long-Term Considerations:

Immunosuppression may affect platelet function
Recurrent disease can recreate coagulopathy
Metabolic syndrome increases thrombotic risk

Emerging Therapies and Future Directions

Direct Oral Anticoagulants (DOACs)

Recent studies suggest selected DOACs may be safe and effective in liver disease:

Rivaroxaban: Most studied, appears safe in Child-Pugh A-B
Apixaban: Emerging data suggest feasibility
Dabigatran: Avoid in liver disease (hepatotoxicity concerns)

Selection Criteria:

Child-Pugh Class A or stable B
No active bleeding
Stable renal function
Ability to monitor adherence

Pearl 5: The DOAC Revolution

DOACs may revolutionize anticoagulation in liver disease. Early studies show similar efficacy to LMWH with potentially better patient compliance and quality of life.

Thrombopoietin Receptor Agonists

Avatrombopag and Lusutrombopag:

FDA-approved for thrombocytopenia in liver disease
Enable procedures without platelet transfusion
May have additional hemostatic benefits beyond platelet count

Factor VIIa and Other Hemostatic Agents

Recombinant Factor VIIa:

Reserved for life-threatening bleeding
High thrombotic risk
Requires adequate fibrinogen and platelets to be effective

Desmopressin (DDAVP):

May improve platelet function
Useful in mild bleeding disorders
Monitor for hyponatremia

Practical Guidelines and Protocols

ICU Management Protocol

Initial Assessment:

Obtain TEG/ROTEM within 6 hours of admission
Assess for both bleeding and thrombotic risk factors
Establish baseline hemostatic function

Monitoring:

Daily conventional coagulation tests
TEG/ROTEM every 48-72 hours or with clinical change
Serial imaging for thrombosis surveillance

Intervention Thresholds:

Bleeding: MA/MCF <40mm, active hemorrhage
Thrombosis Prevention: High-risk patients regardless of INR
Procedure Preparation: Individualized based on procedure risk and patient factors

Hack 5: The ICU Dashboard

Create a simple bedside tool: Green light (proceed with procedures/anticoagulation), Yellow light (proceed with caution/TEG guidance), Red light (high risk, subspecialty consultation). Base it on TEG/ROTEM rather than PT/INR.

Anticoagulation Decision Algorithm

Portal Vein Thrombosis in Liver Disease:

Acute PVT + Active Bleeding → Supportive care, re-evaluate in 48-72h
Acute PVT + No Active Bleeding → Start prophylactic LMWH, advance based on TEG/ROTEM
Chronic PVT + Transplant Candidate → Therapeutic anticoagulation essential
Chronic PVT + Not Transplant Candidate → Risk-benefit assessment, consider anticoagulation

Monitor: Anti-Xa levels, repeat imaging at 3 months, assess bleeding complications

Common Pitfalls and How to Avoid Them

Oyster 3: The Volume Overload Trap

FFP contains 200-250 mL per unit. A 70kg patient needing "INR correction" often receives 4-6 units (1000+ mL), potentially precipitating pulmonary edema and increasing portal pressure.

Oyster 4: The Platelet Transfusion Reflex

Platelets in liver disease are often larger and more functional than normal platelets. A count of 50,000 may be more effective than 100,000 normal platelets. Don't transfuse based on numbers alone.

Oyster 5: The Anticoagulation Phobia

Many physicians are reluctant to anticoagulate patients with liver disease due to elevated INR. This leads to preventable thrombotic complications, including hepatic decompensation from portal vein thrombosis.

Cost-Effectiveness and Resource Utilization

Economic Impact

Traditional Management:

Average FFP cost per liver disease admission: $2,500-4,000
ICU length of stay: 7-10 days
Complication rate: 25-35%

Viscoelastic-Guided Management:

Initial TEG/ROTEM cost: $150-300 per test
Reduced blood product utilization: 40-60% reduction
Shorter ICU stay: 5-7 days average
Complication rate: 15-25%

Return on Investment:

Break-even point: 3-4 patients per month
Annual savings potential: $100,000-500,000 per center

Pearl 6: The Business Case

TEG/ROTEM implementation requires initial investment but pays for itself quickly through reduced blood product use, shorter ICU stays, and fewer complications. Present this data to hospital administrators.

Quality Metrics and Outcomes

Key Performance Indicators

Process Measures:

Time to viscoelastic testing in liver disease patients
Appropriate use of blood products (indication-specific)
Anticoagulation initiation in high-risk patients

Outcome Measures:

Bleeding complications post-procedure
Thrombotic events during admission
Length of stay
Mortality
Blood product utilization

Patient-Centered Outcomes:

Quality of life measures
Functional status at discharge
Hospital readmission rates

Case-Based Learning: Putting It All Together

Case 1: The Complex Cirrhotic

Presentation: A 48-year-old woman with hepatitis C cirrhosis, Child-Pugh Class C, presents with massive hematemesis. Initial labs: INR 3.2, platelets 35,000/μL, hemoglobin 6.1 g/dL, fibrinogen 89 mg/dL.

TEG Results:

R-time: 12.3 minutes (prolonged)
K-time: 4.8 minutes (prolonged)
α-angle: 42° (reduced)
MA: 38 mm (reduced)
LY30: 24% (hyperfibrinolysis)

Management:

Immediate: Tranexamic acid 1g IV, fibrinogen concentrate 3g IV
Secondary: Single unit platelets, avoid FFP initially
Monitoring: Repeat TEG in 4 hours
Outcome: Bleeding controlled without FFP, avoided volume overload

Teaching Point:

This case illustrates how viscoelastic testing identifies specific defects (hyperfibrinolysis, low clot strength) allowing targeted therapy rather than empiric blood product administration.

Case 2: The Anticoagulation Dilemma

Presentation: A 62-year-old man with alcoholic cirrhosis develops extensive portal vein thrombosis after admission for ascites. No active bleeding, but INR 2.1 makes team hesitant to anticoagulate.

TEG Results:

R-time: 8.2 minutes (normal)
MA: 52 mm (normal)
LY30: 0.2% (hypofibrinolysis)

Decision: Despite elevated INR, TEG shows adequate hemostatic function with reduced fibrinolysis (thrombotic tendency). Initiated therapeutic LMWH.

Outcome: Thrombus resolution at 3 months, no bleeding complications.

Teaching Point:

TEG/ROTEM can identify patients safe for anticoagulation despite abnormal conventional parameters, preventing potentially catastrophic thrombotic complications.

Research Frontiers and Future Directions

Artificial Intelligence and Predictive Modeling

Machine Learning Applications:

Bleeding risk prediction models incorporating multiple variables
Real-time decision support systems
Personalized anticoagulation dosing algorithms

Promising Developments:

Integration of genomic markers
Continuous hemostatic monitoring devices
Point-of-care artificial intelligence interpretation

Novel Therapeutic Targets

Microparticle Modulation:

Cell-derived microparticles play roles in both bleeding and clotting
Potential therapeutic targets for hemostatic balance

Complement System:

Emerging role in liver disease coagulopathy
Novel therapeutic interventions under investigation

Endothelial Function:

Central role in hemostatic balance
Potential for targeted therapies

Pearl 7: The Future is Now

AI-assisted coagulation management is already being tested. Soon, bedside algorithms may integrate TEG/ROTEM data with clinical variables to provide real-time, personalized recommendations.

Conclusions and Clinical Pearls

The management of coagulopathy in liver disease requires abandoning outdated paradigms based on conventional coagulation testing in favor of comprehensive hemostatic assessment. The key principles include:

Recognize Rebalanced Hemostasis: Liver disease affects both pro- and anti-coagulant systems proportionally
Utilize Viscoelastic Testing: TEG/ROTEM provides superior guidance compared to PT/INR
Treat Function, Not Numbers: Base interventions on clinical evidence and functional testing
Consider Thrombotic Risk: These patients face significant clotting complications despite elevated INR
Use Targeted Therapies: Factor concentrates and antifibrinolytics are often superior to FFP
Individualize Anticoagulation: Many liver disease patients benefit from anticoagulation despite abnormal conventional parameters

Final Pearl: The Paradigm Shift

The coagulopathy of liver disease is not a bleeding disorder—it's a hemostatic imbalance that requires nuanced, individualized management. Success comes from understanding the underlying pathophysiology and using appropriate diagnostic tools to guide therapy.

References

Tripodi A, Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365(2):147-156.
Lisman T, Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood. 2010;116(6):878-885.
Northup PG, McMahon MM, Ruhl AP, et al. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006;101(7):1524-1528.
Caldwell SH, Hoffman M, Lisman T, et al. Coagulation disorders and hemostasis in liver disease: pathophysiology and critical assessment of current management. Hepatology. 2006;44(4):1039-1046.
Stravitz RT, Lisman T, Luketic VA, et al. Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography. J Hepatol. 2012;56(1):129-136.
Reverter JC, Tàssies D, Font J, et al. Hypercoagulable state in patients with cirrhosis demonstrated by thrombin generation assay. Hepatology. 2003;37(4):873-879.
Tripodi A, Primignani M, Chantarangkul V, et al. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006;44(2):440-445.
Ferro D, Quintarelli C, Saliola M, et al. Prevalence of hyperfibrinolysis in patients with liver cirrhosis. Eur J Clin Invest. 1993;23(12):747-752.
Tufano A, Coppola A, Cerbone AM, et al. Increased thrombin generation in patients with cirrhosis is related to an imbalance of pro- vs anticoagulant factors. Clin Gastroenterol Hepatol. 2009;7(9):1034-1040.
Kumar M, Ahmad J, Maiwall R, et al. Thromboelastography-guided blood component use in patients with cirrhosis with nonvariceal bleeding: a randomized controlled trial. Hepatology. 2020;71(1):235-246.
De Pietri L, Bianchini M, Montalti R, et al. Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: a randomized, controlled trial. Hepatology. 2016;63(2):566-573.
Rout G, Shalimar, Gunjan D, et al. Thromboelastography-guided blood product transfusion in cirrhosis patients with variceal bleeding: a randomized controlled trial. J Hepatol. 2020;73(2):234-243.
Drolz A, Horvatits T, Roedl K, et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology. 2016;64(2):556-568.
Lisman T, Caldwell SH, Burroughs AK, et al. Hemostasis and thrombosis in patients with liver disease: the ups and downs. J Hepatol. 2010;53(2):362-371.
Hugenholtz GC, Northup PG, Porte RJ, Lisman T. Is there a rationale for treatment of chronic liver disease patients with anticoagulant therapy? Blood Rev. 2015;29(2):127-136.
Youssef WI, Salazar F, Dasarathy S, et al. Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study. Am J Gastroenterol. 2003;98(6):1391-1394.
Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S.
Northup PG, Garcia-Pagan JC, Garcia-Tsao G, et al. Vascular liver disorders, portal vein thrombosis, and procedural bleeding in patients with liver disease: 2020 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;73(1):366-413.
Intagliata NM, Henry ZH, Maitland H, et al. Direct oral anticoagulants in cirrhosis patients pose similar risks of bleeding when compared to traditional anticoagulation. Dig Dis Sci. 2016;61(6):1721-1727.
Lee HF, Chan YH, Chang SH, et al. Effectiveness and safety of non-vitamin K antagonist oral anticoagulant and warfarin in cirrhotic patients with nonvalvular atrial fibrillation. J Am Heart Assoc. 2019;8(15):e011112.
Hum J, Shatzel JJ, Jou JH, Deloughery TG. The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis. Eur J Haematol. 2017;98(4):393-397.
Hoolwerf EW, Kraaijpoel N, Büller HR, et al. Direct oral anticoagulants vs vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation: a systematic review and meta-analysis. Eur Heart J. 2021;42(36):3747-3757.
Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP. Oral anticoagulation in patients with liver disease. J Am Coll Cardiol. 2018;71(19):2162-2175.
Serper M, Weinberg EM, Cohen JB, et al. Mortality and hepatic decompensation in patients with cirrhosis and atrial fibrillation treated with anticoagulation. Hepatology. 2021;73(1):219-232.
Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017;66(6):1313-1326.
Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome. Gastroenterology. 2006;130(7):2031-2038.
Sarin SK, Philips CA, Kamath PS, et al. Toward a comprehensive new classification of portal vein thrombosis in patients with cirrhosis. Gastroenterology. 2016;151(4):574-577.
Benmassaoud A, Salti J, Martinez M, et al. Clinical and economic outcomes associated with thromboelastography versus standard coagulation tests among cirrhosis patients undergoing invasive procedures. J Gastroenterol Hepatol. 2023;38(2):241-248.
Rout G, Gunjan D, Singh V, et al. Thromboelastography-guided blood product transfusion in cirrhosis patients undergoing high-risk procedures: a randomized controlled trial. Dig Dis Sci. 2021;66(7):2394-2404.
Mallett SV. Clinical utility of viscoelastic tests of coagulation (TEG/ROTEM) in patients with liver disease and during liver transplantation. Semin Thromb Hemost. 2015;41(5):527-537.
Krzanicki D, Sugavanam A, Mallett S. Intraoperative hypercoagulability during liver transplantation as demonstrated by thromboelastography. Liver Transpl. 2013;19(8):852-861.
Hartmann M, Walde C, Dirkmann D, et al. Safety of coagulation factor concentrates guided by ROTEM-analyses in liver transplantation: results from 372 procedures. BMC Anesthesiol. 2019;19(1):97.
Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev. 2016;2016(8):CD007871.
Gonzalez E, Moore EE, Moore HB, et al. Goal-directed hemostatic resuscitation of trauma-induced coagulopathy: a pragmatic randomized clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg. 2016;263(6):1051-1059.
Bolliger D, Görlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology. 2010;113(5):1205-1219.
Hunt BJ, Allard S, Keeling D, et al. A practical guideline for the haematological management of major haemorrhage. Br J Haematol. 2015;170(6):788-803.
Spahn DR, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98.
Rossaint R, Afshari A, Bouillon B, et al. The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80.
Schöchl H, Nienaber U, Hofer G, et al. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care. 2010;14(2):R55.
Kashuk JL, Moore EE, Sawyer M, et al. Postinjury coagulopathy management: goal directed resuscitation via POC thrombelastography. Ann Surg. 2010;251(4):604-614.
Ak K, Isbir CS, Tetik S, et al. Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: a prospective randomized study. J Card Surg. 2009;24(4):404-410.
Shore-Lesserson L, Manspeizer HE, DePerio M, et al. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg. 1999;88(2):312-319.
Weber CF, Görlinger K, Meininger D, et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology. 2012;117(3):531-547.
Dias JD, Sauaia A, Achneck HE, et al. Thromboelastography-guided therapy improves patient blood management and certain clinical outcomes in elective cardiac and liver surgery and emergency resuscitation: a systematic review and analysis. J Thromb Haemost. 2019;17(6):984-994.
Baumgarten A, Wilhelmi M, Kalbantner K, et al. Evaluation of platelet function analyzer (PFA-100) and thromboelastometry in healthy volunteers. Platelets. 2009;20(1):38-44.
Mallett SV, Chowdary P, Burroughs AK. Clinical utility of viscoelastic tests of coagulation in patients with liver disease. Liver Int. 2013;33(7):961-974.
Zanetto A, Senzolo M, Vitale A, et al. Thromboelastometry hypercoagulable profiles and portal vein thrombosis in cirrhotic patients with hepatocellular carcinoma. Dig Liver Dis. 2017;49(4):440-445.
Zanetto A, Campello E, Spiezia L, et al. Cancer-associated thrombosis in cirrhotic patients with hepatocellular carcinoma. Cancers (Basel). 2018;10(11):450.
Hugenholtz GC, Adelmeijer J, Meijers JC, et al. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology. 2013;58(2):752-761.
Feys HB, Canciani MT, Peyvandi F, et al. ADAMTS13 activity to antigen ratio in physiological and pathological conditions associated with an increased risk of thrombosis. Br J Haematol. 2007;138(4):534-540.

Tuesday, August 26, 2025