How do APTEM (Activated Partial Thromboplastin Time), EXTEM (Extrinsic coagulation pathway test), ROTEM (Rotational Thromboelastometry), and FIBTEM (Fibrinogen contribution test) differ from each other and how are they conducted?

ROTEM Assays: Differentiation and Methodology

Overview of ROTEM vs Individual Assays

ROTEM (Rotational Thromboelastometry) is not a single test but rather a platform that encompasses multiple specific assays including EXTEM, FIBTEM, APTEM, and INTEM (not APTEM alone), each designed to evaluate different components of the coagulation cascade. 1, 2

Individual ROTEM Assays and Their Specific Functions

EXTEM (Extrinsic Pathway Test)

• Activator: Tissue factor (thromboplastin) 1, 2
• Purpose: Evaluates the extrinsic coagulation pathway, providing rapid assessment of overall clot formation 1, 2
• Clinical utility: Detects hyperfibrinolysis when maximum lysis (ML) >15%, particularly useful in postpartum hemorrhage where 23% of women in resource-limited settings demonstrate this pattern 1
• Key parameters measured: Clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) 1, 3

FIBTEM (Fibrinogen Contribution Test)

• Activator: Tissue factor plus cytochalasin D (platelet inhibitor) 1, 2
• Purpose: Isolates fibrinogen's contribution to clot formation by eliminating platelet contribution 1
• Clinical utility: Highly predictive of fibrinogen levels, with FIBTEM A10 showing correlation of r=0.87 (p<0.001) with fibrinogen concentration 4
• Critical threshold: FIBTEM A5 ≤12 mm correlates with fibrinogen ≤2.0 g/L and predicts need for fibrinogen replacement in postpartum hemorrhage 1
• Rapid results: Provides clinically actionable information within 15-20 minutes, significantly faster than Clauss fibrinogen assays 1, 4

APTEM (Fibrinolysis Assessment Test)

• Activator: Tissue factor plus aprotinin (fibrinolysis inhibitor) 1, 2
• Purpose: Specifically evaluates the fibrinolytic pathway by comparing results with EXTEM 1, 2
• Interpretation: If APTEM corrects abnormalities seen in EXTEM (particularly ML >15%), this confirms hyperfibrinolysis as the underlying mechanism 5
• Clinical application: Essential for confirming hyperfibrinolysis during liver transplantation, where it serves as the gold standard confirmation test 5

INTEM (Intrinsic Pathway Test)

• Activator: Ellagic acid 1, 2, 6
• Purpose: Evaluates the intrinsic coagulation pathway 1, 2
• Correlation with standard tests: INTEM-CT shows significant moderate to strong correlation with aPTT (activated partial thromboplastin time) 3

How ROTEM Assays Are Conducted

Sample Collection and Preparation

• Blood sample: Whole blood (typically 300-350 μL per test) collected in citrated tubes 7, 6
• Temperature: All tests performed at 37°C, which is a critical limitation as it cannot assess hypothermia effects on coagulation 2, 8
• Timing: Tests should be run within 4 hours of blood collection for optimal accuracy 6

Testing Methodology

• Principle: Blood is placed in a cup with specific reagents; a pin suspended in the blood rotates slowly, and changes in rotational movement are detected as clot forms 1, 6
• Simultaneous testing: Multiple assays (EXTEM, FIBTEM, APTEM, INTEM) can be run simultaneously on the same blood sample 5, 6
• Real-time results: Provides continuous monitoring from clot initiation through propagation to potential lysis 2

Key Parameters Measured Across All ROTEM Assays

Clotting Time (CT)

• Time from test initiation to initial fibrin formation (2mm amplitude) 1, 2, 3
• Reflects coagulation factor activity and corresponds to R time in TEG 1, 8

Clot Formation Time (CFT)

• Time from clot initiation (2mm) to reach 20mm clot width 1, 2
• Correlates significantly with fibrinogen and platelet levels (r = -0.44 to -0.70 for fibrinogen) 7, 3

Alpha Angle

• Angle between horizontal line and tangent to curve at clot initiation point 1
• Can predict later ROTEM parameters (A10 and MCF) and fibrinogen levels 1, 3

Maximum Clot Firmness (MCF)

• Maximum amplitude of clot strength measured in millimeters 1, 2
• Reflects combined contributions of platelets and fibrinogen to clot stability 2, 3
• Strong correlation with fibrinogen (r = 0.49 to 0.73) and platelets (r = 0.41 to 0.56) 7, 3

Clot Lysis Parameters

• CL30 (clot lysis at 30 minutes) and CL60 (at 60 minutes) after MCF 1
• Maximum lysis (ML) = 100 - CL60, with ML >15% defining hyperfibrinolysis 1

Comparative Sensitivity Between Assays

Hyperfibrinolysis Detection

FIBTEM demonstrates superior sensitivity for detecting hyperfibrinolysis compared to EXTEM or standard TEG. In liver transplantation patients, FIBTEM detected 94% (84/89) of hyperfibrinolysis cases, while EXTEM detected only 46% (41/89) and kaolin-TEG detected merely 24% (21/89), with all differences statistically significant (p<0.001) 5

Fibrinogen Assessment

• FIBTEM A10 shows area under curve of 0.96 for predicting fibrinogen <200 mg/dL 4
• FIBTEM parameters (A5, A15, MCF) correlate significantly with fibrinogen levels (r = 0.82, p<0.001) 1

Critical Limitations Across All ROTEM Assays

What ROTEM Cannot Detect

• Endothelial dysfunction: Cannot assess von Willebrand disease or disorders affecting endothelial adherence 1, 2, 9
• Primary hemostasis defects: Bypasses primary hemostasis, making it insensitive to antiplatelet agents and platelet dysfunction 1, 9
• Hypothermia effects: Testing at 37°C cannot assess coagulopathy related to hypothermia 2, 8

Device Variability

• FIBTEM assays show wide variability between ROTEM Delta and Sigma devices 1
• EXTEM, FIBTEM, and APTEM CT values show no correlation between different ROTEM devices 1
• Results are not interchangeable between ROTEM and TEG systems 2, 8

Clinical Application Algorithm

For Acute Hemorrhage Management

1. Run EXTEM and FIBTEM simultaneously at hemorrhage onset 1, 5
2. If FIBTEM A5 <12mm: Administer fibrinogen concentrate (fibrinogen likely <2.0 g/L) 1
3. If EXTEM shows ML >15%: Run APTEM to confirm hyperfibrinolysis 5
4. If APTEM corrects EXTEM abnormalities: Administer tranexamic acid for confirmed hyperfibrinolysis 5

For Coagulation Factor Assessment

• INTEM-CT prolonged: Suggests intrinsic pathway deficiency or heparin effect; correlates with aPTT 3
• EXTEM-CT prolonged: Suggests extrinsic pathway deficiency; moderate correlation with INR 3
• FIBTEM-MCF low with normal EXTEM-MCF: Isolated fibrinogen deficiency 1, 4
• Both EXTEM and FIBTEM-MCF low: Combined platelet and fibrinogen deficiency 3, 4