Lecture 4 - Coagulatio, Anticoag ECHMO Flashcards
Increase hemorrhage can increase the changes of what infection?
sepsis
especially in little neonates
ECMO related complications?
Clots in curcuit
Thrombus
Autopsy findings on ECMO patients showed what?
That the machine is throwing clots even if we don’t see
We see less than 46% (actual) vs 15% (we know about)
What if we only use coated circuits – what were the studies findings?
“There were no effects of (current) biocompatible circuits on mortality after cardiac operations and a limited effects on lower transfusion needs and atrial fibrillation rate”
*The use of biocompatible surfaces without other measures to contain blood activation resulted in limited clinical benefit!
Angry platelets do what?
Angry platelets degranulate causing other platelets and white blood cells to become angry releasing further chemotactic and mitogenic factors in a vicious circle.
(release serotonin, ADP, thromboxane)
•Tissue Factor (TF) is exposed and components of the Intrinsic Pathway (Factors IX, XI, & XII) are activated 2° to RBC and PLT microparticle release
What happens on artificial ECMO surfaces?
•Platelets and monocytes become deposited on “flow eddies” with increasing cytokine release
Organogenesis
The use of heparin-bound systems has unmasked the primary problem of the blood material interface which is platelet adherence to the artificial surface followed by platelet activation, aggregation ect (as low as 40% from baseline) AS ECC time increases so does the acceleration of thrombus and inflammatin
Real endothelial cell has what on the outer surface?
Nitric O
Prostaglandins
Proteases
ADP, Protein S, t-PA, PAF, thrombin
Real endothelium is in a complex chemical dance with platelets
•Endothelium constantly releases NO, prostacyclin(s), and complex proteins which completely inhibit platelets’ abilities to activate
*Platelets can endlessly “slam dance” with endothelium and each contact causes the platelet to do what?
to be temporarily functionally anesthetized
“The combination of controlled NO release as
well as immobilized active thrombomodulin and heparin from/on the same polymeric surface mimics the highly thromboresistant endothelium layer. Hence….????
such multifunctional polymer coatings should provide more blood-compatible surfaces for biomedical devices.
MAYBE SOMEDAY
“The use of NO gas in the sweep flow of the artificial oxygenators used during ECLS…(resulted in) a reduction in platelet consumption, adhesion, and activation…both activation and consumption were?
were reduced…”
The use of NO gas in sweep reducing activation – “This phenomenon demonstrates the non-thrombogenic effect of NO administered through an active membrane, but as of present WHAT?
this has not been applied clinically because the rest of the ECLS circuitry remains thrombogenic.”
Pediatric Critical Care Manual - most ECMO places use what type of circuits?
Sixty-nine of 117 (59%) of respondents …use tip-to-tip or partially heparin-bonded circuits.”
Ideal characteristics for an anticoagulant on ECMO? (5)
1) Inhibits platelet and coagulation system activation within the ECMO circuit while still allowing for normal coagulation activity
2) Titratable to effect
3) Easily and cheaply monitored
4) Easily and cheaply reversed
5) Cheap and easy to use
What type of Heparin is used most on ECMO?
“Unfractionated heparin was (reportedly) used at all centers…”
Typical Protocol with Heparin and ECMO?
-Initial dosage: ~40-80 units/kg
–Maintenance infusion: 10-30 units/kg/hr adjusted according to laboratory values
Normal neonatal ACTS sec?
–“Normal” neonatal = 90-150s
*No normals for “sick” infants have been established!
Bolus heparin to ACT>300 seconds during cannulation (typically 50-150 units/kg if heparin is not used in the blood prime and 40-100 units/kg if heparin is added to the blood prime)
If the patient is not on ECMO bypass within thirty minutes of the initial bolus of Heparin what do you do?
draw another ACT (via the catheter) and give an additional 25-50 units/kg if the
ACT
Once ACT is >300 sec on ECMO what do you do?
Initiate a heparin infusion drip of 10-25 units/kg/hr (start at the low range if the post-bolus ACT is ~300 seconds, start the high end if ACTs ~250 seconds) when the patient’s connected to the circuit
Heparin infusion rates are adjusted to a “maintenance” ACT of what?
of 160-220 seconds
*If the patient is at significant risk for hemorrhage (on ECMO) shoot for ACTs of what?
~160-190 seconds
*If the patient is actively hemorrhaging (on ECMO), ACTs of what?
may need to be lowered to 140-180 seconds
How do you monitor Heparin/ACTs on ECMO?
T1/2? when to run ACTs?
The normal half-life of heparin (~1-2 hours) may be dramatically altered.
- Obtain an ACT as soon as feasible once on bypass
- Obtain ACTs every half-hour (until stable) with “delicate” changes in infusion rate to avoid
Bolus heparin doses of (typically) 10-20 units/kg may be necessary if? (On ECMO)
- The ACT drops below 180 seconds
- Platelets are administered
- FFP is administered
Alternatively, if the patient is being returned to surgery the ACT should be allowed to??
decrease (and be maintained during surgery) in the 150-170 second range
Per Perfusion manual - For a “minor” procedures, anticoagulation withheld how long?
withheld 6 hours pre-procedure 6 hours post-procedure
Per Perfusion manual – *For “major” procedures, anticoagulation withheld how long?
withheld 6 hours pre-procedure and 24 hours post-procedure
The Problems With Using Heparin… (4)
•The ATIII-heparin complex is large enough that it’s relatively ineffective for clot-bound thrombin…
…unlike the direct thrombin inhibitors
-Heparin is inherently responsible for platelet aggregation
-Extended usage can lead to HIT-II devastation
-It has a deleterious effect on AT-III (you’re GONNA lose AT-III)
As ACTs when up the most survivability was at what time frame? (in the Annals of thoracic surgery)
360-420 seconds
This fights ELSO recommendations
“Intermittent, on-demand dosing of AT concentrates in pediatric patients on ECMO for respiratory failure increased AT levels, but??
but not…to the targeted level.”
ACT correlation with Heparin levels
greater R value the greater the correlation
LOW
there is a slightly better correlation with PTT tests and Heparin levels
What AT-III levels to maintain?
“Maintain level between 80-120% of normal”
- 82% routinely or occasionally test for AT-III
- The median AT-III goal was 70% of normal
- Only 1/3rd use AT-III for low-level replacement
AT-III levels varied wildly (much more than closely-controlled heparin levels)
•Also realized AT-III affects what?
much more than thrombin (affects virtually all coagulation enzymes to some degree)
How could the administration of AT-III before Heparin be done?? (for ECMO)
- Continuous AT-III infusion started immediately post-ECMO implantation
- AT-III was maintained at >100% and heparin was not started until this target was reached
Dramatically less bleeding than in the AT-III bolus group
“…significantly reduced surgical revision for bleeding…translated into excellent overall outcomes.”
What is the rate limiting step in anticoagulation?
Essentially, AT-III is the rate-limiting step (not heparin)
*Atryn’s half-life is ?
~~12-18 hours
*Thrombate’s half-life is ?
2.0-3.8 days
So…it’s easier to maintain a therapeutic range with
Thrombate and far less must be used in a constant infusion setting
For the time being, what is the RX of choice for ECMO (anticoag)
Thrombate infusions are now becoming the Rx-of-choice in ECMO (but this might be due to really good marketing by its manufacturer, too!)
3 factor lacks what? (PCC)
factor 7
ex Bebulin
4 factor includes what? (PCC)
factor 7
ex Profilnine
AT III is only approved for what in reality?
only “approved” for hereditary antithrombin deficiency
Many ECLS institutions don’t do what?
many ECLS centers (still) neither test AT activity levels nor give AT concentrate.”
Pentoxiphylline
give to sickly cell patients which decreases blood viscosity
ECMO patient developed HIT-II – what do you use?
Angiomax
Argatroban
Refludan (not that common)
*”Direct thrombin inhibitors…demonstrate more predictable what?
pharmacokinetics and reduce thrombin generation to a greater degree when compared to heparin.
The advantage of acting independent of anti-thrombin make these anticoagulants especially appealing for use in ECLS in infants and children, not just in cases of HIT.”
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