Lecture 4 - Coagulatio, Anticoag ECHMO

Question 1

Increase hemorrhage can increase the changes of what infection?

Answer 1

sepsis

especially in little neonates

Question 2

ECMO related complications?

Answer 2

Clots in curcuit

Thrombus

Question 3

Autopsy findings on ECMO patients showed what?

Answer 3

That the machine is throwing clots even if we don’t see

We see less than 46% (actual) vs 15% (we know about)

Question 4

What if we only use coated circuits – what were the studies findings?

Answer 4

“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!

Question 5

Angry platelets do what?

Answer 5

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

Question 6

What happens on artificial ECMO surfaces?

Answer 6

•Platelets and monocytes become deposited on “flow eddies” with increasing cytokine release

Question 7

Organogenesis

Answer 7

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

Question 8

Real endothelial cell has what on the outer surface?

Answer 8

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

Question 9

*Platelets can endlessly “slam dance” with endothelium and each contact causes the platelet to do what?

Answer 9

to be temporarily functionally anesthetized

Question 10

“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….????

Answer 10

such multifunctional polymer coatings should provide more blood-compatible surfaces for biomedical devices.

MAYBE SOMEDAY

Question 11

“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?

Answer 11

were reduced…”

Question 12

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?

Answer 12

this has not been applied clinically because the rest of the ECLS circuitry remains thrombogenic.”

Question 13

Pediatric Critical Care Manual - most ECMO places use what type of circuits?

Answer 13

Sixty-nine of 117 (59%) of respondents …use tip-to-tip or partially heparin-bonded circuits.”

Question 14

Ideal characteristics for an anticoagulant on ECMO? (5)

Answer 14

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

Question 15

What type of Heparin is used most on ECMO?

Answer 15

“Unfractionated heparin was (reportedly) used at all centers…”

Question 16

Typical Protocol with Heparin and ECMO?

Answer 16

-Initial dosage: ~40-80 units/kg

–Maintenance infusion: 10-30 units/kg/hr adjusted according to laboratory values

Question 17

Normal neonatal ACTS sec?

Answer 17

–“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)

Question 18

If the patient is not on ECMO bypass within thirty minutes of the initial bolus of Heparin what do you do?

Answer 18

draw another ACT (via the catheter) and give an additional 25-50 units/kg if the
ACT

Question 19

Once ACT is >300 sec on ECMO what do you do?

Answer 19

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

Question 20

Heparin infusion rates are adjusted to a “maintenance” ACT of what?

Answer 20

of 160-220 seconds

Question 21

*If the patient is at significant risk for hemorrhage (on ECMO) shoot for ACTs of what?

Answer 21

~160-190 seconds

Question 22

*If the patient is actively hemorrhaging (on ECMO), ACTs of what?

Answer 22

may need to be lowered to 140-180 seconds

Question 23

How do you monitor Heparin/ACTs on ECMO?

T1/2? when to run ACTs?

Answer 23

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

Question 24

Bolus heparin doses of (typically) 10-20 units/kg may be necessary if? (On ECMO)

Answer 24

• The ACT drops below 180 seconds
• Platelets are administered
• FFP is administered

Question 25

Alternatively, if the patient is being returned to surgery the ACT should be allowed to??

Answer 25

decrease (and be maintained during surgery) in the 150-170 second range

Question 26

Per Perfusion manual - For a “minor” procedures, anticoagulation withheld how long?

Answer 26

withheld 6 hours pre-procedure 6 hours post-procedure

Question 27

Per Perfusion manual – *For “major” procedures, anticoagulation withheld how long?

Answer 27

withheld 6 hours pre-procedure and 24 hours post-procedure

Question 28

The Problems With Using Heparin… (4)

Answer 28

•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)

Question 29

As ACTs when up the most survivability was at what time frame? (in the Annals of thoracic surgery)

Answer 29

360-420 seconds

This fights ELSO recommendations

Question 30

“Intermittent, on-demand dosing of AT concentrates in pediatric patients on ECMO for respiratory failure increased AT levels, but??

Answer 30

but not…to the targeted level.”

Question 31

ACT correlation with Heparin levels

greater R value the greater the correlation

Answer 31

LOW

there is a slightly better correlation with PTT tests and Heparin levels

Question 32

What AT-III levels to maintain?

Answer 32

“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

Question 33

AT-III levels varied wildly (much more than closely-controlled heparin levels)
•Also realized AT-III affects what?

Answer 33

much more than thrombin (affects virtually all coagulation enzymes to some degree)

Question 34

How could the administration of AT-III before Heparin be done?? (for ECMO)

Answer 34

• 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.”

Question 35

What is the rate limiting step in anticoagulation?

Answer 35

Essentially, AT-III is the rate-limiting step (not heparin)

Question 36

*Atryn’s half-life is ?

Answer 36

~~12-18 hours

Question 37

*Thrombate’s half-life is ?

Answer 37

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

Question 38

For the time being, what is the RX of choice for ECMO (anticoag)

Answer 38

Thrombate infusions are now becoming the Rx-of-choice in ECMO (but this might be due to really good marketing by its manufacturer, too!)

Question 39

3 factor lacks what? (PCC)

Answer 39

factor 7

ex Bebulin

Question 40

4 factor includes what? (PCC)

Answer 40

factor 7

ex Profilnine

Question 41

AT III is only approved for what in reality?

Answer 41

only “approved” for hereditary antithrombin deficiency

Question 42

Many ECLS institutions don’t do what?

Answer 42

many ECLS centers (still) neither test AT activity levels nor give AT concentrate.”

Question 43

Pentoxiphylline

Answer 43

give to sickly cell patients which decreases blood viscosity

Question 44

ECMO patient developed HIT-II – what do you use?

Answer 44

Angiomax
Argatroban
Refludan (not that common)

Question 45

*”Direct thrombin inhibitors…demonstrate more predictable what?

Answer 45

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.”

Question 46

58/93

Answer 46

58/93