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Harlinde Peperstraete MD
Ghent University Hospital
Harlinde.peperstraete@ugent.be
Anticoagulation
Protein
absorption
albumin
fibrinogen
albumin
fibrinogen
Trombospondin
Fibronectin
VWF
IgE
albumin
fibrinogen
albumin
fibrinogen
Trombospondin
Fibronectin
VWF
IgE
Platelet adsorption
albumin
fibrinogen
albumin
fibrinogen
Trombospondin
Fibronectin
VWF
IgE
Platelet adsorption
GPIIb/IIIa
albumin
fibrinogen
albumin
fibrinogen
Trombospondin
Fibronectin
VWF
IgE
TF
VIIa
VIIa
VIIa
VIIa
TF
TF
TF
TF
VIIa
And so coa...
Contact
activation
Prekalikrein
HMWKalikrein
XI
XIIa
Kalikrein
Bradykinin
3 actions of
bradykinin
• Activation of intrinsic coagulation pathway
• Activation of complement system >
inflammation > a...
Hemolysis
Plasma free Hb enhances interaction
between vWF and platelets
Delicate balance between coagulation and
fibrinolysis
• TFPI-system (Tissue Factor Pathway Inhibitor)
• Intact endothelial...
Unfractionated heparin
• Standard in most centers
• Low cost
• Antidote= protamin
• Familiarity
• Monitoring:
• ACT (140-2...
UFH binds AT
Structural change in AT
Inhibitory power is accelerated
1:1 Xa & IIa
Variability in effect: UFH binds pos
cha...
Antithrombin
• Drop in levels during the first days of ECMO
therapy
• Indicated in heparin resistance
• Daily...?
• Cut of...
Low-
Molecular-
Weight
Heparin
• Anti Xa monitoring (1h before and 4h after
administering)
• Mainly renal clearance, most ...
(parental)
Direct
Thrombin
Inhibitors
• Bivalirudin
• Agratoban
• Short half-lives (30 min and 40 min)
• No antidotes
Bivalirudin
• Direct trombin inhibitor
• HIT pts
• Best monitored with Diluted Thrombin Time
• aPTT 50-90sec (ceiling effe...
Argatroban
• Direct trombin inhibitor
• HIT pts
• Best monitored with Diluted Thrombin Time
• aPTT
• Can interfere with PT...
Antiplatelet
drugs
• Inhibit coagulation at the starting point
• Might reduce platelet consumption
• iNO on oxygenator
No
anticoagulation
• First 24-48h to 7days
• TBI, major bleeding, Disseminated
Intravascular Coagulation
• Waiting for res...
VV ECMO: antico vs no antico (n=646)
Overall: major bleeding 16%, thrombosis 53%
ACT alone target: 62% major bleeding, 62%...
VA ECMO: antico vs no antico (n=1496)
Overall 27% bleeding, 8% Trombo-embolic events
ACT< 180sec 13%, 12% TE
ACT>180sec 28...
Monitoring
coagulation
Combination of ACT, aPTT, anti Xa with
 ATIII
 Platelet count / function
 Fibrinogen
 Viscoelas...
By Adam Morcom
4. anticoagulation during ecmo #beach2019 (peperstraete)
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This workshop will outline the basic principles of extracorporeal life support made easy by key-experts in the field. During the course delegates will gain a good understanding of ECMO in the following areas: Theoretical concepts, basic physiology and pathophysiology, cardiac and respiratory support and monitoring, alarm settings and monitoring, role of cardiac ultrasound during ECMO, newest technologies, circuits and devices, practical hands-on sessions and simulations.

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4. anticoagulation during ecmo #beach2019 (peperstraete)

  1. 1. Harlinde Peperstraete MD Ghent University Hospital Harlinde.peperstraete@ugent.be Anticoagulation
  2. 2. Protein absorption albumin fibrinogen albumin fibrinogen Trombospondin Fibronectin VWF IgE
  3. 3. albumin fibrinogen albumin fibrinogen Trombospondin Fibronectin VWF IgE Platelet adsorption
  4. 4. albumin fibrinogen albumin fibrinogen Trombospondin Fibronectin VWF IgE Platelet adsorption GPIIb/IIIa
  5. 5. albumin fibrinogen albumin fibrinogen Trombospondin Fibronectin VWF IgE TF VIIa VIIa VIIa VIIa TF TF TF TF VIIa And so coagulation is initiated... Leading to activation of factor X and a burst of thrombin formation Important role for Ca2+
  6. 6. Contact activation Prekalikrein HMWKalikrein XI XIIa Kalikrein Bradykinin
  7. 7. 3 actions of bradykinin • Activation of intrinsic coagulation pathway • Activation of complement system > inflammation > activated endothelium > TF • Inflammatory reaction by the kallikrein system Leading to SIRS and vasoplegic state
  8. 8. Hemolysis Plasma free Hb enhances interaction between vWF and platelets
  9. 9. Delicate balance between coagulation and fibrinolysis • TFPI-system (Tissue Factor Pathway Inhibitor) • Intact endothelial cells: ADPase, eNO, PGI2, t-PA • Intact endothelial cells: heparansulfate • Protein C-system (VIIIa & Va) • Protein S • Antithrombin (± heparin) via XIIa, XIa, IXa, Xa & IIa • Fibrinolytic system through fibrinogen & fibrin
  10. 10. Unfractionated heparin • Standard in most centers • Low cost • Antidote= protamin • Familiarity • Monitoring: • ACT (140-220) • APTT (40-80sec or 1.5-2.5 ratio) • Anti-Xa (0.3-0.7) • Viscoelastic tests
  11. 11. UFH binds AT Structural change in AT Inhibitory power is accelerated 1:1 Xa & IIa Variability in effect: UFH binds pos charged proteins !AFP
  12. 12. Antithrombin • Drop in levels during the first days of ECMO therapy • Indicated in heparin resistance • Daily...? • Cut off for substitution...
  13. 13. Low- Molecular- Weight Heparin • Anti Xa monitoring (1h before and 4h after administering) • Mainly renal clearance, most ECMO pts have AKI
  14. 14. (parental) Direct Thrombin Inhibitors • Bivalirudin • Agratoban • Short half-lives (30 min and 40 min) • No antidotes
  15. 15. Bivalirudin • Direct trombin inhibitor • HIT pts • Best monitored with Diluted Thrombin Time • aPTT 50-90sec (ceiling effect), ACT • Bolus: 0.5-0.75 mg/kg • Infusion: 1.75 mg/kg/h • Mainly renal clearance
  16. 16. Argatroban • Direct trombin inhibitor • HIT pts • Best monitored with Diluted Thrombin Time • aPTT • Can interfere with PT • Mainly hepatic clearance
  17. 17. Antiplatelet drugs • Inhibit coagulation at the starting point • Might reduce platelet consumption • iNO on oxygenator
  18. 18. No anticoagulation • First 24-48h to 7days • TBI, major bleeding, Disseminated Intravascular Coagulation • Waiting for resolution of shock • Lubnow M et al. Technical complications during veno-venous extracorporeal membrane oxygenation and their relevance predicting a system-exchange—retrospective analysis of 265 cases. J Crit Care 2014;29:473.e1–473.e5.
  19. 19. VV ECMO: antico vs no antico (n=646) Overall: major bleeding 16%, thrombosis 53% ACT alone target: 62% major bleeding, 62% thrombosis aPTT guided 19% bleeding, 27% thrombosis aPTT<60 8% bleeding, 34% thrombosis aPTT >60 56% major bleeding, 7% thrombosis Thrombosis: mainly circuit clotting Anticoagulation Practices during Venovenous Extracorporeal Membrane Oxygenation for Respiratory Failure. A Systematic Review; MC Sklar e.a. AnnalsATS Volume 13 Number 12; 2242-2250
  20. 20. VA ECMO: antico vs no antico (n=1496) Overall 27% bleeding, 8% Trombo-embolic events ACT< 180sec 13%, 12% TE ACT>180sec 28%, 9% TE APTT target 50%, 3%TE Mixture of methods for monitoring 24% bleeding; 6 % TE 43% bleeding if no antico, 24% TE events Anticoagulation practices and the prevalence of major bleeding, thromboembolic events, and mortality in venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis. E. Sy e.a. Journal of Critical Care; Volume 39, June 2017, Pages 87-9
  21. 21. Monitoring coagulation Combination of ACT, aPTT, anti Xa with  ATIII  Platelet count / function  Fibrinogen  Viscoelastic test (How fast- how strong- for how long?)  NO SINGLE TEST may be considered adequate to guide (UFH) management
  22. 22. By Adam Morcom
  • DwightDumay

    Oct. 13, 2019

This workshop will outline the basic principles of extracorporeal life support made easy by key-experts in the field. During the course delegates will gain a good understanding of ECMO in the following areas: Theoretical concepts, basic physiology and pathophysiology, cardiac and respiratory support and monitoring, alarm settings and monitoring, role of cardiac ultrasound during ECMO, newest technologies, circuits and devices, practical hands-on sessions and simulations.

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