"Functional" Coagulopathy in the ICU – ROTEM/TEG-Based Decision-Making: A Paradigm Shift from Numbers to Function
Abstract
Background: Traditional coagulation tests (PT/aPTT/INR) provide limited information about hemostatic function in critically ill patients, often failing to predict bleeding risk or guide therapeutic interventions effectively. Viscoelastic hemostatic assays (VHA) including Rotational Thromboelastometry (ROTEM) and Thromboelastography (TEG) offer real-time assessment of coagulation dynamics from clot initiation through fibrinolysis.
Objective: This review synthesizes current evidence on VHA-guided coagulation management in critical care, providing practical frameworks for clinical decision-making across diverse ICU scenarios.
Methods: Comprehensive literature review of randomized controlled trials, meta-analyses, and clinical guidelines published between 2015-2025, with focus on trauma, obstetric hemorrhage, liver disease, and DIC management.
Results: VHA-guided algorithms demonstrate reduced blood product utilization, improved patient outcomes, and cost-effectiveness compared to conventional coagulation testing in multiple clinical contexts. Key applications include goal-directed therapy in massive transfusion protocols, personalized anticoagulation reversal, and early detection of hyperfibrinolysis.
Conclusions: Adoption of VHA represents a fundamental shift toward functional coagulation assessment, enabling precision hemostatic therapy in critically ill patients.
Keywords: Viscoelastic testing, ROTEM, TEG, coagulopathy, critical care, precision medicine
Introduction
The traditional approach to coagulation assessment in critical care relies heavily on conventional plasma-based tests developed over five decades ago. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) measure only the initiation phase of coagulation in platelet-poor plasma under non-physiological conditions. These tests fail to capture the complex interplay between cellular and plasma components that determine hemostatic competence in vivo.¹
This disconnect between laboratory values and clinical bleeding risk has profound implications. Studies consistently demonstrate poor correlation between PT/aPTT prolongation and surgical bleeding, with normal values failing to exclude bleeding risk and abnormal values poorly predicting hemorrhage.²,³ Furthermore, these tests provide no information about clot strength, platelet function, or fibrinolysis – critical determinants of hemostatic adequacy.
Viscoelastic hemostatic assays (VHA) emerged as a solution to these limitations, offering comprehensive real-time assessment of coagulation dynamics. Unlike static endpoint measurements, VHA evaluates the entire hemostatic process from clot initiation through dissolution, providing actionable information for targeted interventions.
The Science Behind Viscoelastic Testing
Fundamental Principles
VHA measures the viscoelastic properties of blood as it coagulates, generating continuous data about clot formation, strength, and breakdown. The technique involves placing a small blood sample between two surfaces – one stationary, one oscillating – and measuring resistance changes as coagulation progresses.
Both ROTEM and TEG operate on similar principles but differ in technical execution. ROTEM uses a pin suspended in a cup, while TEG employs a pin-and-cup system with the cup oscillating. These mechanical differences result in distinct parameter nomenclature but equivalent clinical information.
Key Parameters and Clinical Correlations
Clotting Time (CT/R-time): Time from test initiation to clot formation onset. Prolonged values suggest factor deficiencies or anticoagulant effects. Normal ranges: ROTEM CT 100-240 seconds, TEG R-time 5-10 minutes.
Clot Formation Time (CFT/K-time): Time from clot initiation to 20mm amplitude. Reflects fibrinogen function and platelet aggregation. Prolonged values indicate fibrinogen deficiency or platelet dysfunction. Normal CFT: 30-110 seconds, K-time: 1-3 minutes.
Alpha Angle: Slope of clot formation curve, representing rate of clot strengthening. Decreased values suggest fibrinogen or platelet deficiencies. Normal ranges: 70-83 degrees (ROTEM), 53-72 degrees (TEG).
Maximum Clot Firmness (MCF/MA): Peak clot strength, primarily determined by platelet count and function, with fibrinogen contributing significantly. Reduced values indicate thrombocytopenia, platelet dysfunction, or hypofibrinogenemia. Normal MCF: 50-72mm, MA: 50-70mm.
Lysis Index (LI30/LY30): Percentage amplitude reduction at 30 minutes post-MCF, indicating fibrinolytic activity. Elevated values suggest hyperfibrinolysis requiring antifibrinolytic therapy. Normal LI30: >92%, LY30: <8%.
Clinical Pearls: Reading VHA Traces
Pearl #1: The "Pancake" Pattern – Flat, wide traces with prolonged CFT and reduced MCF suggest severe hypofibrinogenemia. Think postpartum hemorrhage or massive transfusion dilution.
Pearl #2: The "Needle" Pattern – Narrow traces with rapid rise but poor MCF indicate platelet dysfunction despite adequate count. Common in uremia or antiplatelet therapy.
Pearl #3: The "Dissolving" Pattern – Normal formation followed by rapid amplitude decline suggests hyperfibrinolysis. Consider tranexamic acid in trauma or obstetric bleeding.
Clinical Applications: From Theory to Bedside
Trauma-Induced Coagulopathy
Trauma-induced coagulopathy (TIC) affects 25-35% of severely injured patients, significantly increasing mortality risk.⁴ Traditional massive transfusion protocols rely on fixed ratios of blood products, often resulting in over-transfusion or inadequate hemostatic support.
VHA enables personalized resuscitation by identifying specific coagulation defects:
Hyperfibrinolysis (30% of TIC cases): Detected by LY30 >3% or LI30 <85%. Requires immediate tranexamic acid administration. Early recognition prevents the "death spiral" of continued bleeding and consumption.
Fibrinogen Deficiency: Alpha angle <65° or CFT >240 seconds indicates need for fibrinogen concentrate or cryoprecipitate. Target fibrinogen levels >1.5-2.0 g/L in active bleeding.
Platelet Dysfunction: MCF <45mm despite adequate platelet count suggests qualitative defect requiring platelet transfusion or desmopressin.
Teaching Point: The ROTEM-guided TASH study demonstrated 30% reduction in blood product use with improved survival compared to conventional management.⁵ This represents the power of functional assessment over laboratory-driven protocols.
Postpartum Hemorrhage
Obstetric bleeding presents unique coagulation challenges due to physiological changes of pregnancy and delivery. Conventional tests often remain normal despite significant bleeding, creating clinical uncertainty.
VHA provides critical insights:
Hyperfibrinolysis: Common in placental abruption and amniotic fluid embolism. LY30 >15% indicates severe hyperfibrinolysis requiring high-dose tranexamic acid (2-4g).
Acquired Fibrinogen Deficiency: Alpha angle <65° or prolonged CFT suggests consumption. Early fibrinogen replacement (target >2g/L) improves outcomes.
DIC Evolution: Progressive deterioration of all parameters indicates developing consumption coagulopathy requiring aggressive component therapy.
Oyster Alert: Normal fibrinogen levels (2-4g/L) in pregnancy may still represent relative deficiency if VHA shows functional impairment. Trust the trace, not just the number.
Liver Disease Coagulopathy
Patients with chronic liver disease present complex hemostatic alterations affecting both pro- and anticoagulant pathways. Traditional tests suggest bleeding tendency due to prolonged PT/INR, but VHA reveals a more nuanced picture.
Rebalanced Hemostasis: Despite prolonged CT, many patients maintain normal MCF due to elevated factor VIII and reduced ADAMTS13. This "rebalancing" explains why bleeding risk doesn't correlate with INR elevation.
Thrombocytopenia Compensation: Reduced platelet count is often offset by increased platelet aggregation and elevated von Willebrand factor, maintaining adequate MCF.
Hyperfibrinolysis Risk: Elevated tissue plasminogen activator with reduced antiplasmin creates bleeding tendency detectable by increased LY30.
Clinical Hack: Use VHA before invasive procedures in cirrhotic patients. Normal MCF despite elevated INR suggests adequate hemostatic reserve, potentially avoiding unnecessary transfusions.
Disseminated Intravascular Coagulation
DIC represents a complex syndrome of simultaneous thrombosis and bleeding. VHA provides real-time assessment of the dynamic balance between coagulation and fibrinolysis.
Compensated DIC: Prolonged CT with maintained MCF suggests ongoing consumption with adequate compensatory synthesis.
Decompensated DIC: Progressive deterioration of all parameters indicates consumption exceeding synthesis, requiring aggressive component therapy.
Hyperfibrinolytic Phase: Elevated LY30 indicates dominant fibrinolytic activity requiring antifibrinolytic therapy alongside component replacement.
Evidence-Based Algorithms: Translating Traces to Actions
ROTEM-Guided Therapy Algorithm
Step 1: Assess Clot Initiation (CT/R-time)
- CT >240s (R >10 min): Consider FFP 10-15 mL/kg or PCC 25-50 U/kg
- Severe prolongation: Rule out heparin effect with heparinase test
Step 2: Evaluate Clot Formation (CFT, Alpha Angle)
- CFT >240s or Alpha <45°: Fibrinogen concentrate 25-50 mg/kg or cryoprecipitate 1-2 units/10kg
- Target: Alpha angle >65°, CFT <240s
Step 3: Assess Clot Strength (MCF/MA)
- MCF <45mm (MA <45mm): Platelet transfusion 1 unit/10kg or desmopressin 0.3 μg/kg
- Consider platelet function if count adequate but MCF reduced
Step 4: Monitor Fibrinolysis (LY30/LI30)
- LY30 >3% (LI30 <85%): Tranexamic acid 1g IV, repeat if necessary
- Severe hyperfibrinolysis (LY30 >15%): Consider higher doses or aminocaproic acid
TEG-Guided Decision Tree
Similar principles apply with parameter adjustments:
- R-time >10 minutes → Factor replacement
- K-time >3 minutes or Alpha <53° → Fibrinogen therapy
- MA <50mm → Platelet support
- LY30 >3% → Antifibrinolytic therapy
Advanced Applications and Emerging Concepts
Anticoagulation Reversal
VHA enables personalized reversal strategies for patients on anticoagulant therapy requiring urgent procedures or experiencing bleeding.
Warfarin Reversal: CT normalization confirms adequate reversal, avoiding over-correction with excessive PCC dosing.
DOAC Reversal: Specific antidotes (idarucizumab, andexanet alfa) can be monitored for effectiveness using VHA parameters.
Heparin Management: Heparinase-modified tests distinguish heparin effect from factor deficiency, guiding protamine dosing.
Cardiac Surgery Applications
VHA has revolutionized coagulation management in cardiac surgery, where complex interactions between cardiopulmonary bypass, hypothermia, and anticoagulation create unique challenges.
Post-Bypass Bleeding: VHA identifies specific defects (platelet dysfunction, fibrinolysis, factor dilution) enabling targeted therapy rather than empirical transfusion.
Protamine Titration: Real-time assessment of heparin neutralization prevents protamine excess and associated complications.
Pediatric Considerations
Children present unique challenges due to developmental differences in hemostatic system maturation. Reference ranges vary significantly with age, requiring pediatric-specific algorithms.
Neonatal Coagulopathy: Immature fibrinogen synthesis affects VHA parameters differently than adult patterns.
Congenital Deficiencies: VHA can identify specific factor deficiencies in bleeding children when conventional tests are inconclusive.
Quality Assurance and Limitations
Technical Considerations
Sample Quality: Citrated samples must be tested within 4 hours, with temperature and pH affecting results. Poor venipuncture technique or delayed processing compromises accuracy.
Standardization: Different activators (kaolin, tissue factor, ellagic acid) provide complementary information but require interpretation experience.
Training Requirements: VHA interpretation requires dedicated education and ongoing competency assessment. Misinterpretation can lead to inappropriate interventions.
Clinical Limitations
Point-of-Care Constraints: While rapid (10-30 minutes), VHA still requires time for complete analysis during active bleeding emergencies.
Cost Considerations: Higher per-test costs compared to conventional tests, though offset by reduced blood product utilization and improved outcomes.
Anticoagulation Interference: Some medications (particularly direct thrombin inhibitors) can produce artifacts requiring careful interpretation.
Teaching Frameworks for Residents
The "CLOT" Mnemonic
Clotting Time – Factor deficiency or anticoagulation Length of formation – Fibrinogen function Optimal strength – Platelet function and count Time to dissolution – Fibrinolytic activity
Clinical Teaching Scenarios
Scenario 1: 25-year-old female, postpartum hemorrhage, BP 80/40, Hgb 6.0
- VHA shows: Normal CT, prolonged CFT, reduced alpha angle, normal MCF, elevated LY30
- Interpretation: Hyperfibrinolysis with mild fibrinogen dysfunction
- Action: Immediate tranexamic acid 2g IV, fibrinogen concentrate if available
Scenario 2: 45-year-old male, polytrauma, ongoing bleeding despite 6 units RBC
- VHA shows: Prolonged CT, normal CFT/alpha, reduced MCF, normal LY30
- Interpretation: Combined factor and platelet deficiency
- Action: FFP 4 units + platelets 6 units (or balanced blood product ratio)
Common Resident Errors
Error #1: Treating numbers instead of patterns. Teaching point: A single abnormal parameter rarely tells the whole story.
Error #2: Ignoring clinical context. VHA guides therapy but doesn't replace clinical judgment about bleeding source control.
Error #3: Over-correcting normal variants. Some patients have constitutionally different baselines requiring individual interpretation.
Cost-Effectiveness and Resource Utilization
Multiple studies demonstrate VHA-guided therapy reduces blood product utilization by 20-40% while improving clinical outcomes.⁶,⁷ The DETECT study showed significant cost savings despite higher testing costs, with reduced ICU length of stay and transfusion-related complications.
Economic Pearl: The average cost of VHA-guided therapy is offset by preventing just one inappropriate platelet transfusion or avoiding one transfusion reaction requiring extended hospitalization.
Future Directions and Emerging Technologies
Artificial Intelligence Integration
Machine learning algorithms show promise for automated VHA interpretation, potentially reducing interpretation variability and improving accuracy. Early studies suggest AI can identify subtle patterns missed by human analysis.
Microfluidic Devices
Next-generation point-of-care devices using microfluidic technology promise even faster results with smaller sample volumes, potentially enabling true bedside testing within minutes.
Personalized Hemostasis
Genetic profiling combined with VHA may enable individualized bleeding risk assessment and tailored prophylactic strategies for high-risk procedures.
Conclusions
The integration of ROTEM and TEG into critical care practice represents more than technological advancement – it embodies a fundamental shift toward functional medicine. By moving beyond static laboratory values to dynamic hemostatic assessment, clinicians can provide personalized, evidence-based coagulation management.
The evidence overwhelmingly supports VHA-guided therapy across diverse clinical scenarios, from trauma resuscitation to obstetric emergencies. Reduced blood product utilization, improved patient outcomes, and cost-effectiveness make adoption not just clinically beneficial but economically prudent.
For the next generation of critical care physicians, mastering VHA interpretation is essential. The ability to "think functionally" about coagulation – understanding how clots form, strengthen, and dissolve in real-time – enables precision interventions that static tests cannot guide.
As we advance toward an era of personalized medicine, VHA provides the foundation for individualized hemostatic therapy. The future lies not in treating laboratory abnormalities but in optimizing physiological function based on comprehensive understanding of each patient's unique coagulation profile.
Key Clinical Pearls Summary
- Trust the Trace: VHA patterns often reveal functional abnormalities despite normal conventional tests
- Context Matters: Same VHA abnormality may require different interventions based on clinical scenario
- Think Stepwise: Address clot initiation, formation, strength, and fibrinolysis systematically
- Early Intervention: VHA enables proactive therapy before complete coagulation failure
- Monitor Response: Serial VHA can guide therapy titration and assess intervention effectiveness
References
Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228-232.
Levy JH, Dutton RP, Hemphill JC 3rd, et al. Multidisciplinary approach to the challenge of hemostasis. Anesth Analg. 2010;110(2):354-364.
Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8(9):2063-2065.
Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma. 2003;54(6):1127-1130.
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.
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.
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.
Hunt H, Stanworth S, Curry N, et al. Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) for trauma induced coagulopathy in adult trauma patients with bleeding. Cochrane Database Syst Rev. 2015;(2):CD010438.
Bolliger D, Görlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology. 2010;113(5):1205-1219.
Hartmann M, Szalai C, Saner FH. Hemostasis in liver transplantation: Pathophysiology, monitoring, and treatment. World J Gastroenterol. 2016;22(4):1541-1550.
Conflict of Interest: The authors declare no competing interests.
Funding: This work received no specific funding.
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