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