COAGULATION ISSUES ON ECMO 2010
Endothelial activationThrombin / clot formationAction of heparinBleeding protocolClinical relevance
CLOTS IN CIRCUIT• 29% of neonates
BLEEDING• 41% of neonates• 28% of children• 45% of cardiac
patients• 47% of adults
Incidence of bleeding (ELSO 1998)
• Fibrinogen adsorption• Platelet activation• Contact activation• Thrombin generation despite heparin• Plasminogen activation• Continued thrombotic stimulus
Why does blood clot when exposed to an ECMO circuit?
Clotting cascade
Activates contact pathway factor 12
Protein monolayer
Fibrinogen adsoprtion on circuit
• Any foreign surface is thrombogenic• Fibrinogen coats foreign surface or damaged endothelium• Occurs in thick dense MOLOLAYER (1000 x concentration of plasma)• Process is unpredicatble : different tissues / different time period
factor 12
fibrinogen
+
Contact PATHWA
Y
Cytokinesplatelets
“Contact Activation”
Platelet activation
Fibrinogen
Platelet(non activated)
Activated platelet
Thrombin binding site
Endothelium
CYTOKINES
AntithrombinProtein CProtein STissue factor inhibitor
Thrombin
Anticoagheparin
thrombinplatelet
ANTICOAGULANT
Thrombin generation
PRO-COAGULANT
Thrombin
Fibrinogen 3. Fibrin
A
B Insoluble fibrin
4. tPA can dissolve
1.Platelets
2. Factor X111
crosslinked
Fibrin formation via thrombin (PROCOAGULANT)
Fibrinogen / platelet mesh
• Heparin unable to get into monolayer• Accelerates antithrombin x 1000• No effect on platelets
Procoagulant surface overwhelming
heparin
Action of Heparin as ANTICOAGULANT
Antithrombin IIIProtein CProtein STissue factor inhibitor
Thrombin
ANTICOAGULANTS
Procoag
Thrombin activated fibrin
fibrin
Heparin thrombin interaction
Clot formationThrombogenic
surface
ThrombinProtein CProtein STissue factor inhibitor
Heparin
fibrinogen
CLOT
Antithrombin
platelets
fibrin
History ECMO
Action of Heparin: Clotting cascade
Heparin does not dissolve clots
Clot formation
Anticoagulants
• Massive tissue factor release on ECMO• Overwhelming procoagulant state• Platelets and thrombin activated• Fibrinogen meshwork forms
• HEPARIN DOES NOT DISSOLVE CLOTS
• HEPARIN PREVENTS NEW CLOTS FORMING
HEPARIN ANTICOAGULATION
1 unit of heparin (the "Howell Unit") is an amount required to keep 1 mL of cat's blood fluid for 24 hours at 0°C.
Heparin
• Standard unfractionated heparin will be used for routine anticoagulation for all children on ECMO
• Standard concentration of 1ml = 20u/kg/hr(20 x wt x 50u Heparin in 50ml 0.9% saline)
• Heparin dose at cannulation = 75u/kg (on surgeons instructions)
• Start infusion of 20 u/kg/hr when ACT < 300• Maintain ACT between 160 -180 seconds and
monitor and record ACT's HOURLY
Standard Heparin Anticoagulation
Ann Thorac Surg 2007;83:912–20
ASAIO Journal 2007; 53:111-114
Wide variation between ACT’sAnd heparin delivery betweenPatients and in same patient
ACT vs Anti Xa levels with heparin
ACT’s do NOT reflect anticoagulation cascade with accuracy
DO NOT interpret in isolation
Always recheck abnormal values
Increasing heparin to target value• Bolus 25u/kg and escalate dose by 5u/kg/hr until target ACT
reached • Measure ACT every 15 min till ACT Target achieved • If > 50ug/kg/hr heparin is needed then check antithrombin level • Platelet transfusions may increase requierments for ECMO
Decreasing heparin to target value• Reduce by 5u/kg/hr until target ACT reached. • Measure ACT every 15 min until Target reached • DO NOT STOP HEPARIN regardless of ACT (see bleeding
protocol and discuss with ECMO lead)
Targeting Heparin effect with ACT
• Standard ACT target 160 to 180 sec• Bleeding (reduce heparin) 140 to 160 sec• Major Bleeding add Tranexamic acid
• Microdose heparin don’t use ACT10 u/kg/hr
Bleeding protocol
van der Staak,F.H. et al J Ped Surg 1997;32(4):594-599
• Reduced surgical bleedingo (57 v 390 mL, P = .005)
• Lower RBC transfusion o (1.13 v 2.95 mL/kg/h, P = .03).
• 2 patients with severe thrombotic complications
• Dose o bolus 4 mg/kg o infusion of 1 mg/kg/h
Tranexamic acid
Bleeding protocol: Last resort: Factor 7
Clot formation: Patient or circuit
If ECMO flow stopped for > 5 minutes: consider thrombus risk
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