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Anticoagulation during mechanical support by Dr Sara Allen
The document discusses current recommendations for anticoagulation during ECMO, emphasizing individualized approaches based on patient conditions and clinical contexts. It highlights the importance of monitoring and adjusting heparin dosages, discusses alternatives like direct thrombin inhibitors, and outlines protocols for managing complications such as bleeding and thrombosis. Additionally, it addresses specific cases and considerations for patients with various complications during mechanical support.
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Anticoagulation during mechanical support by Dr Sara Allen
- 1. Anticoagulation During Mechanical Support SaraJane Allen CVICU, Auckland City Hospital
- 5. ECMO and Anticoagulation • Whatare the current recommendations? • Anticoagulation • Measurement • What are the potential problems? • Differences between VV and VA ECMO
- 7. Bleeding • Patient’s criticalillness • Surgery • SIRS • Activated coagulation cascade • Anticoagulation Clotting • Patient’s critical illness • Surgery • SIRS • Activated coagulation cascade • Extracorporeal circuit and cannula • Underlying cardiac function
- 8. Bleeding • Patient’s criticalillness • Surgery • SIRS • Activated coagulation cascade • Anticoagulation Clotting • Patient’s critical illness • Surgery • SIRS • Activated coagulation cascade • Extracorporeal circuit and cannula • Underlying cardiac function
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- 19. Current ELSO Recommendations • Correctcoagulopathy prior to ECMO (platelets, INR, fibrinogen) • Bolus heparin on cannulation/initiation of ECMO • Heparin continuous infusion during ECMO
- 20. • Heparin 20-50units/kg/hour ongoing infusion • Aim for ACT 180-220 seconds • Adjust doses according to clinical context (recent CPB, bleeding, residual heparin effect) • Individualise approach to monitoring of anticoagulation • Use more than one method
- 22. • Monitor heparinwith ACT * • Consider monitoring of anti-Xa activity (gold standard of heparin effect) and antithrombin III levels • May use APTT • Use of TEG beneficial to assess heparin resistance, platelet function, components of coagulation
- 23. • Antithrombin III •Optimal level of AT III activity for anticoagulation during ECMO is unknown • If escalating heparin doses or clear resistance, measure AT III levels and anti-Xa activity • Replace (AT concentrates) if < 50% activity * • Heparinase TEG in conjunction may be useful (assess heparin effect)
- 24. • Anti Xaassay • Specific to heparin effect * • Independent of coagulopathy, thrombocytopenia, anaemia • May be falsely lowered by hyperlipidaemia, hyperbilirubinaemia, haemolysis (high plasma free Hb) • Most assays target 0.3 - 0.7 IU/mL (assay variation) • Correlation with ACT targets on daily basis in some centres
- 25. • Alternatives toheparin are direct thrombin inhibitors (bivalirudin, lepirudin, argatroban) • Many potential advantages • Predictable PK (independent of antithrombin, do not bind other plasma proteins) • Predictable dosing, monitor with APTT • Greater reduction of thrombin generation (inhibit clot bound and circulating thrombin) • No reversal (major limitation!)
- 26. • Potential futureanticoagulants • NOACs • Factor XIIa inhibitor • Further circuit biocompatibility (NO, prostacyclin releasing polymers) • Not in clinical use at present
- 27. • Define ableeding threshold (may vary between patient groups) • Suggested targets • Haematocrit 0.35-0.40 • INR < 1.5-2.0 • Fibrinogen > 1.0 - 1.5 g/L • Platelets > 100 x 109/L
- 29. Our Practice -General • All patients before and during ECMO • Platelets > 80 x 109/L • INR < 1.5 • Fibrinogen > 1.5 g/L • Measured minimum 12 hourly • Targets individualised (e.g., higher platelets if bleeding)
- 30. Our Practice -VV • Heparin • Bolus on cannulation • 50-100 units per kg • Typically 1000 - 5000 units • Individualised for clinical context (e.g., coagulopathy, bleeding)
- 31. Our Practice -VV • Heparin • Continuous infusion, fixed dose 10 units/kg/hour • Commenced when ACT < 300 (or much lower!) • Stop if excessively high ACT (>160) or bleeding • No action if low ACT (and circuit, plasma Hb normal) • Flows > 3 L/min
- 33. Our Practice -VV • Increase heparin dose to target ACT if • Circuit clot burden high • Elevated plasma free Hb > 1000 mg/L • Post oxygenator PaO2 <15 kPa (post “coughing”) • Reducing flows for normal pump speeds • Pressure drop across oxygenator high (>50mmHg)
- 34. Our Practice -VA • Heparin • Bolus on cannulation for ECMO • 50-100 units per kg • Typically 5000 units • Individualised for clinical context (e.g., following CPB, bleeding)
- 35. Our Practice -VA • Heparin • Continuous infusion, titrated to ACT 140-180 • Commenced when ACT < 300 * • Flows > 3 L/min • If bleeding, may aim for lower ACT target • If high risk cardiac stasis, may aim for higher ACT target • During weaning studies, aim for higher ACT target (low flows)
- 36. Our Practice -VA • Post CPB • Full heparin reversal once established on ECMO • Allows adequate surgical haemostasis • Restart heparin subsequently (may be 12- 48 hours later) • May be low dose (5-10 units/kg/hour initially)
- 37. Our Practice -General • Measure plasma free Hb 12 hourly • Use TEG to evaluate potential problems • AT III levels and anti-Xa activity if high heparin doses (>40 units/kg/hour) or resistance concerns • Heparin resistance (AT III < 40%, anti-Xa < 0.3 IU/mL) treated with antithrombin concentrates and heparin dose reduced concurrently (expected increase in heparin effect)
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- 41. • 18 yearold with dilated cardiomyopathy • Heart transplant performed • Primary graft failure • Central VA ECMO commenced • Bleeding excessively • Given multiple blood products (platelets, cryoprecipitate, FFP) • Bleeding ongoing
- 42. Problems? • Should fullprotamine be given? • Should ECMO be run with or without heparin? • Is it safe to give factor VIIa in this circumstance?
- 43. • Full protaminereversal • No heparin infusion used • No factor VIIa used
- 44. 6 hours later •Progressive hypotension • Low flows/high pump speed • Chatter on ECMO circuit lines • Intermittent suckdowns • No pulsatility on arterial line waveform
- 45. • Re-exploration ofchest in CVICU • Coagulation parameters normal except • Moderate heparin effect (ACT 160s APTT 51) • Given protamine 50mg
- 49. What should bedone? • Nothing - futile ongoing therapy? • Heparinise? • Thrombolysis? • Return to OR? • Thrombus excision • Atrial septostomy? • LV vent?
- 50. Taken back toOR • Excision of clot via aorta, AV and LA • Atrial septostomy performed • Attempt to minimise intracardiac stasis • Returned to ICU • Increased inotropes (increased ejection) • Therapeutically anticoagulated • Flows maintained > 3 L/min
- 51. Progress • Weaned fromVA ECMO on day 5 • Weaned from mechanical ventilation on day 15 • Full neurological recovery • Ongoing renal failure (CVVH/SLEDD) • Discharged to ward on day 21 on IHD
- 52. Discussion • Severe LVdysfunction is high risk for intracardiac stasis • Can happen and progress very rapidly • Worsened by extrinsic compression • Higher risk in peripheral VA ECMO than central VA ECMO • Anticoagulation balance different for these patients • May require other interventions: ongoing inotropes, septostomy, or LV venting (surgical or Impella) • Can still achieve good outcomes
- 53. Bleeding - Early •No heparin • Safe for prolonged periods for VV ECMO • Caution during VA ECMO if • severe cardiac dysfunction (minimal ejection) • peripheral VA cannulation (inadequate LV decompression) • periods of low flows or compression of cardiac chambers (tamponade)
- 54. Bleeding - Early •Normalise coagulation parameters • Surgical haemostasis (“buy in”) • If fibrinolysis - consider tranexamic acid • Extreme caution with factor VIIa • Reports of catastrophic thromboses
- 56. Procedures • Higher bleedingrisk than in other critically ill patients • Even when coagulation parameters “normal” • Avoid if at all possible • Use oral route rather than nasal for enteral tubes • Tracheostomies only once weaned from ECMO • Interrupt anticoagulation if procedure necessary
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- 59. • 34 yearold • Day 16 VV ECMO for influenza A • Stable course “single organ failure” • Today temperature 374 • Bleeding from NJ, NG, at cannula sites (new) • No new requirement for inotrope
- 60. • Platelets 96x 109/L • INR 1.6 • Fibrinogen 2.6 g/L
- 62. Problems? • Should tranexamicacid be given? • What else needs investigating?
- 63. • Tranexamic wouldbe appropriate as the TEG is consistent with primary fibrinolysis • Investigate the circuit • May indicate high clot burden in the circuit • Plasma free haemoglobin • Post oxygenator PaO2
- 65. Bleeding - Late •Bleeding onset patient previously stable, consider • Sepsis and DIC - no antifibrinolytic • Circuit failure and fibrinolysis - TEG guidance • Primary hyperfibrinolysis - fibrinolytic indicated
- 66. HITT • Uncommon (<0.6%ICU patients) • High false positive for ELISA immunoassay (PF4 antibodies) • Pre-test probability score using “4Ts” best • If 4T moderate or high risk and positive screen - discuss with lab +/- haematologist • Dilution testing • Functional assay in some centres
- 67. HITT • Requires alternativeanticoagulation strategy • No heparin • Fondaparinux 2.5 - 5.0 mg SC daily (patient) • Monitor anti-Xa activity • Bivalirudin (circuit)
- 68. Thrombosis • Common • ELSORegistry thrombosis necessitating circuit change occur in 20% patients • High incidence occult thromboembolic events in autopsy studies (>70%) • Increased risk with increased duration of ECMO • Vigilance following wean and decannulation important too (limb ischaemia or compromise) • May need surgical intervention
- 69. Potential Problems • Excessivebleeding - early and late • Severe LV impairment • VA versus VV ECMO • Thromboses • Procedures • Fibrinolysis - sepsis • Contraindication to heparin - HITTS
- 72. Ventricular Assist Devicesand Anticoagulation • What are the current recommendations? • Measurement • What are the potential problems? • Short term • Long term • Other factors to bear in mind
- 73. Recommendations • Established bymanufacturers and VAD centres • Vary somewhat by device • Three main devices at present • Heart Mate II LVAD (Abbott) • Heart Mate 3 LVAD (Abbott) • HeartWare HVAD (Medtronic)
- 74. Anticoagulation - HeartWare HVAD •During implantation with heparin (ACT >400s) • Full reversal protamine at completion surgery • Normalise coagulation parameters • Caution with factor VIIa • Early commencement heparin (day one) if no bleeding • Target APTT 50-80 (varies with institution)
- 75. Anticoagulation - HeartWare HVAD •Commence aspirin from day 1 if stable • Consider platelet function TEG day 10-14 • Commencement warfarin after day 3 if stable • INR 2.0 to 3.0
- 76. Problems - Bleeding •Immediate bleeding risks post cardiac surgery • Managed intraoperatively in standard manner • Ongoing risk related to anti-platelet and anticoagulant therapy • Additional risk related to • Acquired von Willebrand disease • Gastrointestinal arteriovenous malformations
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Editor's Notes
- #3 Here is Auckland City Hospital, where I work. We are a moderate sized ECMO centre, doing between approximately 50 cases per year. We are a small VAD centre, and only have funding for long term (bridge to transplant) VAD implantation. Today I am going to be discussing anticoagulation for ECMO and long term VADs, I am not going to be discussing balloon pumps, short term VADs or Impellas. I am also limiting this update to adult patients.
- #4 So I am going to talk a lot about ECMO and a little about VADs.
- #5 So I am going to talk a lot about ECMO and a little about VADs.
- #7 The key message with anticoagulation and ECMO is that it is a fine balance - not too much clotting (the circuit, cannula, patient), not too much bleeding (the patient). Bleeding versus clotting. It’s the age old dilemma with ECMO and the safety zone varies considerably depending on the mode of ECMO and the patient. PHOTO: Nik Wallenda crossing the Niagara Falls in 2012.
- #8 The exposure to the extracorporeal circuit and the underlying critical illness promote a systemic inflammatory and coagulation response, leading to a state of hypercoagulation, whilst the systemic inflammatory and coagulation response within the patient also may increase bleeding.
- #9 The exposure of blood continually to the extracorporeal circuit and the underlying critical illness promote a systemic inflammatory and coagulation response, leading to a state of hypercoagulation, promoting thrombosis, whilst the systemic inflammatory and coagulation response within the patient also may increase bleeding, along with injuries or surgical site bleeding. The exact balance of these factors will differ between patients depending on underlying illness and other factors such as cardiac function and propensity for intracardiac and intravascular stasis. Anticoagulation is required most of the time, to prevent the thrombotic complications, but does increase the risk of bleeding and it can be very difficult to get the balance right (prevent thrombosis in patient and circuit, prevent bleeding in patient).
- #10 Here are the internationally agreed consensus guidelines for anticoagulation during ECMO. As you can see, it is a reasonably short list……
- #11 Here are the internationally agreed consensus guidelines for anticoagulation during ECMO. As you can see, it is a reasonably short list……
- #12 Evidence for a particular anticoagulation strategy is reasonably limited, variable and not compelling. A review article, published by some of the doyens of blood and coagulation in ECMO, stated…
- #13 Evidence for a particular anticoagulation strategy is reasonably limited, variable and not compelling. A review article, published by some of the doyens of blood and coagulation in ECMO, stated…
- #15 A systematic review of the literature to date in 2016, concluded…..
- #16 A systematic review of the literature to date in 2016, concluded…..
- #17 Finally last year, an international survey of practice was conducted. It also concluded…
- #18 Finally last year, an international survey of practice was conducted. It also concluded…
- #20 So far, so not controversial. However, ELSO suggest starting continuous heparin infusion when ACT drops below 300 seconds.
- #23 ACT supported as method of monitoring heparin effect as: POC, inexpensive, rapid, reliable and proven over many years (CPB), incorporates both red blood cells and platelets function. Accepting potential limitations that may occur with anaemia, hypofibrinogenemia, thrombocytopenia and other coagulation factor deficiencies, as well as hypothermia.
- #24 Natural inhibitor of serine proteases especially thrombin and factor Xa. * Some centres replace to much higher levels. Replace with AT concentrates preferred (volume and reliability - FFP less reliable).
- #25 Anti Xa activity a measure of heparin’s effect in helping AT III inhibit coagulation. Specific to heparin effect, although heparin (and fibrin formation) not the only important part of haemostats and coagulation for patients on ECMO. - target 0.3-0.7 IU/mL. NB: Anti Xa assays may vary so care with “universal target”. Anti Xa assay not affected by coagulopathy, thrombocytopenia or dilution.
- #26 Independent of antithrombin so not affected by low or varying levels (from liver synthesis or dilution or other methods). Increased efficacy as inhibit both clot bound and circulating thrombin. But lack of easy reversibility. Also not widely available in all centres (lepirudin limited availability). Use APTT 1.5-2.0 times normal as monitor, or anti-IIa levels if available.
- #27 An animal study using an antibody to Factor-XIIa as the anticoagulant for use in ECLS circuits was compared to UNFH anticoagulation. The Factor XIIa antibody prevented fibrin deposition and thrombus development as efficiently as UNFH. However, unlike UNFH, this antibody therapy did not impair the hemostatic capacity, nor did it increase clinical bleeding from wounds (2014).
- #28 ELSO suggest a bleeding threshold of 1 or more units RBC per 24 hours, or more than 20 g/L drop in haemoglobin over 24 hours or more than 20mL/kg blood loss per 24 hours.
- #29 ELSO is based in the USA, and many of the recommendations are understandably broad based on the range of practice and lack of evidence. So, how do we do things down at this end of the world? I thought it useful to talk about what we do in our ICU.
- #30 In consensus with the ELSO guidelines, we correct existing coagulopathy (as much as is feasibly possible) before initiating ECMO.
- #32 We also use heparin as ongoing anticoagulation, but we commence this at a lower ACT than the ELSO guidelines would suggest, and typically at lower doses. We aim for lower ongoing ACT also, particularly for VV ECMO.
- #34 Normal pressure drop < 10mmHg.
- #62 TEG - fibrinolysis
- #65 If the TEG had shown this, a more appropriate course of action would have been cultures, +/- antibiotics, and no tranexamic acid.
- #67 4T score - 6-8 points is high probability. (Thrombocytopenia severity, Timing, Thrombosis, Other causes for thrombocytopenia). Functional assay - serotonin release assay or heparin induced platelet assay.
- #71 Thank you.
- #73 Other factors to bear in mind = acquired VW disease and AVMs for gut bleeding and bleeding during procedures/surgeries. DDAVP at transplant or explant.
- #81 Or thrombosis of VAD pump and management - thrombolysis or surgical treatment. Brief reports/evidence on use of thrombolysis in this instance.