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Bleeding

Direct Oral Anticoagulants

DOAC Assessment Where Drug Levels Assays ARE Available

The International Society on Thrombosis and Haemostasis recommends consideration of anticoagulant reversal for patients with serious bleeding and a DOAC level >50 ng/mL, and for patients requiring an invasive procedure with high bleeding risk and a DOAC level >30 ng/mL

DOAC Assessment Where Drug Levels ARE NOT Available

Test

Interpretation

Dabigatran

TT or aPTT

Normal TT excludes clinically relevant levels

Normal aPTT usually excludes clinically relevant levels

Apixaban

anti-FXa Activity

Undetectable anti-FXa activity probably excludes clinically relevant levels

Normal PT and aPTT DO NOTexclude clinically relevant levels

Rivaroxaban

ROTEM

Simple Rapid MTP ROTEM Algorhythm

ROTEM Parameters

ROTEM

Description

TEG

A5

Amplitude at 5min from CT

A5

A10

Amplitude at 10min from CT

A10

CT

Time to 2mm Amplitude

R

CFT

Time from 2mm to 20mm Amplitude

K

ɑo

Angle of tangent at 2mm amplitude

 

 

Angle of slope between R and K

ɑo

MCF

Maximum Clot Firmness
Maximum Amplitude

MA

MCF-t

Time at MCF
Time to Maximum Amplitude

TMA

LOT

Lysis Onset Time
(15% drop from MCF)

 

 

Clot Lysis Time
(2mm drop from MA)

CLT

LT

Lysis Time
(time until drop to 10% of MCF)

 

 

Lysis Index at 30min
(% drop in amplitude at 30 min)

LI30

ML

Maximum Lysis
(% drop from MCF at any point in time)

 

ROTEM/ TEG

Description

A5/ A5

Amplitude at 5min from CT

A10/ A10

Amplitude at 10min from CT

CT/ R

Time to 2mm Amplitude

CFT/ K

Time from 2mm to 20mm Amplitude

ɑo

Angle of tangent at 2mm amplitude

ɑo

Angle of slope between R and K

MCF/ MA

Maximum Clot Firmness
Maximum Amplitude

MCF-t/ TMA

Time at MCF
Time to Maximum Amplitude

LOT

Lysis Onset Time
(15% drop from MCF)

CLT

Clot Lysis Time
(2mm drop from MA)

LT

Lysis Time
(time until drop to 10% of MCF)

LI30

Lysis Index at 30min
(% drop in amplitude at 30 min)

ML

Maximum Lysis
(% drop from MCF at any point in time)

ROTEM Reference Ranges1,2

 

CT

CFT

A5

A10

A20

MCF

CLI30

ML

INTEM

137-246s

40-100s

38-57s

44-68s

50-71s

55-72mm

94-100%

0-12%

EXTEM

42-74s

46-148s

39-66s

43-65s

50-69s

49-71mm

95-100%

0-18%

FIBTEM

43-69s

 

6-22s

9-24s

8-21s

9-25mm

 

Ranges are for general guidance only. Ideally reference ranges should be set up and validated for each individual centre

ROTEM Reference Ranges1,2

 

INTEM

EXTEM

FIBTEM

CT

137-246s

42-74s

43-69s

CFT

40-100s

46-148s

 

A5

38-57s

39-66s

6-22s

A10

44-68s

43-65s

9-24s

A20

50-71s

50-69s

8-21s

MCF

55-72mm

49-71mm

9-25mm

CLI30

94-100%

95-100%

 

ML

0-12%

0-18%

 

Ranges are for general guidance only. Ideally reference ranges should be set up and validated for each individual centre

Factors Contributing to ROTEM Parameters

ROTEM Test

Test Target

Comments

INTEM

Intrinsic Pathway

Phospholipid and Ellagic acid used as activators to provides information similar to APTT

EXTEM

Extrinsic Pathway

Tissue Factor used as activator to provides information similar to PT

FIBTEM

Fibrinogen

Platelet inhibitor (Cytochalasin D) used to block platelet contribution to clot formation and isolate fibrinogen effect

HEPTEM

Heparin Effect

Contains heparinase to neutralise heparin effect

APTEM

Fibrinolysis

Contains apoprotinin to inhibit fibrinolysis

ECATEM

Thrombin Time

Uses ecarin to activate prothrombin. Sensitive to presence of Direct Thrombin Inhibitors (ie dabigatran)

ROTEM Tests
test target

INTEM
Intrinsic Pathway

Phospholipid and Ellagic acid used as activators to provides information similar to APTT

EXTEM
Extrinsic Pathway

Tissue Factor used as activator to provides information similar to PT

FIBTEM
Fibrinogen

Platelet inhibitor (Cytochalasin D) used to block platelet contribution to clot formation and isolate fibrinogen effect

HEPTEM
Heparin Effect

Contains heparinase to neutralise heparin effect

APTEM
Fibrinolysis

Contains apoprotinin to inhibit fibrinolysis

ECATEM
Thrombin Time

Uses ecarin to activate prothrombin. Sensitive to presence of Direct Thrombin Inhibitors (ie dabigatran)

Typical Coagulation Abnormalities on ROTEM3

Pathology

Features on ROTEM

Suggested Management

Platelet Failure

  • Thrombocytopenia
  • Severe Platelet Dysfunction
  • GPIIb/IIIa Inihibitor

A5EX < 35mm
and
A5FIB ≥ 9mm

Give Platelets

Fibrin Polymerization Disorder

  • Hypofibrinogenaemia
  • low fXIII

A5EX < 35mm
and
A5FIB < 9mm

Give Cryoprecipitate

Intrinsic Pathway Failure

  • Heparin
  • Severe Shock
  • Sepsis

Prolonged CT on INTEM

If due to heparin effect corrects on HEPTEM

Give FFP if Factor Defiency

Give Protamine if Heparin Effect

Extrinsic Pathway Failure

  • Warfarin
  • Liver Failure

Prolonged CT on EXTEM

Give PCC / FFP

Hyperfibrinolysis

  • Trauma-induced Coagulopathy
  • Post-Cardiopulmonary Bypass
  • Heat Stroke

MLEX ≥ 15%
or
MLFIB ≥ 10%

within 60min (LI60 ≤ 85%)

Give Tranexamic Acid

Typical Coagulation Abnormalities on ROTEM3

Pathology

Features on ROTEM

Platelet Failure

  • Thrombocytopenia
  • Severe Platelet Dysfunction
  • GPIIb/IIIa Inihibitor

A5EX < 35mm
and
A5FIB ≥ 9mm

Give Platelets

Fibrin Polymerization Disorder

  • Hypofibrinogenaemia
  • low fXIII

A5EX < 35mm
and
A5FIB < 9mm

Give Cryoprecipitate

Intrinsic Pathway Failure

  • Heparin
  • Severe Shock
  • Sepsis

Prolonged CT on INTEM

If due to heparin effect corrects on HEPTEM

Give FFP if Factor Defiency

Give Protamine if Heparin Effect

Extrinsic Pathway Failure

  • Warfarin
  • Liver Failure

Prolonged CT on EXTEM

Give PCC / FFP

Hyperfibrinolysis

  • Trauma-induced Coagulopathy
  • Post-Cardiopulmonary Bypass
  • Heat Stroke

MLEX ≥ 15%
or
MLFIB ≥ 10%

within 60min (LI60 ≤ 85%)

Give Tranexamic Acid

4
5 6 7 8

References

  1. Multi-centre investigation on reference ranges for ROTEM Thromboelastometry - Blood Coagulation and Fibrinolysis 2005
  2. Baseline parameters for rotational thromboelastometry (ROTEM) in healthy women undergoing elective caesarean delivery - Int J Obs 2019
  3. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management - KJA 2019
  4. The Utility of Thromboelastography in Inherited and Acquired Bleeding Disorders - BJA 2016
  5. Management of Severe Perioperative Bleeding - ESA Guidelines - EJA 2017
  6. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants - JACC 2020
  7. Reversal of direct oral anticoagulants - Guidance from the Anticoagulation Forum - Am J Haematol 2019
  8. A European consensus statement on the use of four-factor PCC for Cardiac and Non-Cardiac Surgical Patients - Anaesthesia 2020
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