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Perf Tech II (exam 2) > Topic 8 Management of postop bleeding > Flashcards

Topic 8 Management of postop bleeding Flashcards

1
Q

Heparin that becomes protein bound:

A

-Unavailable for reversal
-May become free post-CPB
“HEPARIN REBOUND”

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2
Q

Excess Protamine induces

A

Induce bleeding

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3
Q

Hemodilution what % decrease is there in circulating factors ?

A

Appx 25-35% decrease in circulating factors

Institution dependent

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4
Q

Sources of Post Op Bleeding (7)

A 
-Reduced concentration of coagulation
factors
-Hyperfibrinolysis
-Thrombocytopenia
-Impaired Platelet Aggregation
-Platelet Fragmentation
-Loss of Membrane Receptors
-Increased inflammation after CPB impairs
coagulation and increases blood loss
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5
Q

Extrinsic Factor of Post Op Bleeding (4)

A
  • Residual Heparin / Heparin Rebound
  • Excessive Protamine
  • Hemodilution
  • Hypothermia
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6
Q

Prevention of Post-Op Bleeding

A
  • Avoiding CPB
  • Improved biocompatibility of foreign surfaces
  • Alter conduct of bypass
  • Use hematologic strategies
  • Harvest whole blood / Plasma/PRP
  • Improved surgical technique
  • Making sure labs are normal pre-op
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7
Q

Heparin has mild fibrinolytic effect

A

-Stimulates release of serum urokinase
plasminogen activator (UPA)
-Induces fibrinolysis

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8
Q

Tissue Plasminogen Activator (TPA)

A

-More potent than UPA.
-Primary activator of fibrinolysis during
heart surgery.

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9
Q

Large surge of what after protamine is

given

A

TPA

At the time of greatest thrombin production

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10
Q

If left unchecked, could result in large scale
clotting or diffuse intravascular
coagulation.

A

TPA (i.e.. No fibrinolysis)

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11
Q

Thrombin Produced/Surges when?

A
  • Produced throughout CPB
  • Surge @ termination of bypass
  • Surge after protamine administration
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12
Q

Thrombin

A

-Amplifier protein
-Activates many cell lines
-Inflammation
-Coagulation
-Fibrinolysis
-Metabolically active in sites where
heparin cannot reach it

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13
Q

Plasminogen Activator Inhibitor 1 (PAI-1)

 - regulates?
 - released by?
A
  • Regulates TPA

- Released by Liver and Endothelial Cells

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14
Q

Plasminogen Activator Inhibitor 1 (PAI-1)

-binds to what?

A
  • PAI-1 binds to TPA as it’s exported from endothelial cells
    • Therefore, TPA must over comecirculating
    • Initiate fibrinolysis
    • Buffer to surges of TPA
    • Released in response to inflammatory mediators
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15
Q

Plasminogen Activator Inhibitor 1 (PAI-1)

A
  • is Prothrombic
    -Overcomes and suppresses fibrinolytic effect
    of TPA
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16
Q

How does PAI-1 overcomes and supresses finbrinolytic effect of TPA?

A

-Thrombin–makes clot
-TPA breaks up clot PAI-1 prevents TPA from breaking down clots
›Hemostasis!

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17
Q

TPA directly cleaves ?

A

plasminogen-> Plasmin

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18
Q

When TPA cleaves plasminogen to plasmin what happens? (3)

A
  • Exposes Lysine binding sites
  • Fibrinogen and fibrin bind @ these lysine binding sites
  • Proteolytic attack leads to breakdown products
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19
Q

TPA breaks apart what?

A
  • Breaks apart fibrin and therefore, the clot

- Leads to post-op bleeding

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20
Q

Fibrin

A

crosslinks platelets to make a clot

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21
Q

Antifibrinolytic Agents

A

Lysing Analogs
›Aminocaproic Acid (ACA) / Amicar
›Tranexamic Acid (TA)
Aprotinin

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22
Q

Antifibrinolytic Agents

Lysing Analogs

A

›Aminocaproic Acid (ACA) / Amicar ›Tranexamic Acid (TA)

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23
Q

Aminocaproic Acid (ACA) / Amicar

A

Antifibrinolytic Agents

  • 2 lysine molecules stuck together
  • Competitively binds to lysine sites of plasminogen/ plasmin
  • Prevents Plasmin from binding to fibrinogen/fibrin
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24
Q

Aprotinin is?

A

Antifibrinolytic Agent

  • 58 amino acid polypeptide
  • Single Lysine>High affinity for plasmin at this site
  • Non-specific serine protease inhibitor
  • Has other actions
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25
Aprotinin catalyzes what?
Catalyzes multiple reactions of inflammation, | coagulation, and other cellular attack mechanisms
26
2 commercially available lysine analogs
ACA and TA Clinically available for 40+ years
27
Lysine Analogs Pharmavology
- IV Administration - Uptake is immediate - Small, water-soluble molecules
28
Where are Lysine Analogs Distributed ?
Distributed readily into extravascular water spaced before being taken up into various cells and tissues.
29
TA specific pharmacology?
Weak protein-bound | ›Crosses BBB and Placenta
30
Lysine Analogs excretion
Renal excretion
31
Lysine Analogs T1/2
Half-life: 1-2 hours with IV administration
32
ACA loading dosing
Loading Dose: 75-150mg/kg (5-10gm in adults)
33
ACA IV infusion dose?
IV Infusion: 10-15mg/kg/hr | ›Continues until end of CPB or until Protamine is given
34
ACA Pump dose
Pump Dose: 2-2.5g/L ›Some add/ some don’t ›Makes sense to add b/c of added plasma volume on pump
35
ACA Daily, et al Protocol (aka: “10-10-10”) dosing?
›10g given as slow bolus (5-10min) pre-CPB ›10g in CPB prime ›10g after CPB
36
ACA dosing Pt with kidney disease
›Normal/reduced LD ›Reduced continuous infusion rate ACA: 5mg/kg/hr TA: 0.5mg/kg/hr
37
ACA timing of initial dose
-As early as induction and incision -Reports of clot formation on PA Catheter and EKG ST-segmen changes ›Await full anticoagulation with heparin prior to administration
38
TA stand for?
Tranexamic Acid
39
Tranexamic Acid what is it?
Antifibrinolytic agent | Lysing Analogs
40
TA Loading Dose:
10-15mg/kg over 10-15min
41
TA Infusion Dose:
1-1.5mg/kg/hr
42
TA Pump Dose
2-2.5mg/L
43
TA doses compared to ACA dose
1/7 to 1/10th of ACA
44
what is DIC?
Disseminated intravascular coagulopathy/tion or less commonly as consumptive coagulopathy, - pathological process characterized by the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body. This leads to compromise of tissue blood flow and can ultimately lead to multiple organ damage.
45
Lysing Analogs Side affects in DIC patients
Intravascular Clots
46
Lysing Analogs Side affects in Thromboembolic Complications (5)
``` ›Reduced Graft Patency ›DVT ›PE ›Stroke ›MI ›**All theoretically possible after heparin neutralization, but no association has been found ```
47
Patients at low risk for transfusion (despite CPB) may not benefit from what type of drugs? (something to consider)
--- may not benefit from prophylactic anti-fibrinolytics. But may help tip the scales between transfusion or not if they are on the fence.
48
Aprotinin - structure? | found where?
- 58 amino acid polypeptide - Found in all mammalian lung tissue - Isolated from bovine lung
49
Aprotinin activated site?
-contains single lysine -Binding site for most serine proteases it inhibits
50
KIU
Kilo international units
51
Aprotinin: Full Hammersmith Regimen (Most common) -- pump/pt/infusion?
›2 million KIU in pump ›2 million KIU to pt over 30-60 minutes ›500,000 KIU/hr infusion for pump run
52
Aprotinin T1/2
5 hours with this regimen | ›Renal excretion
53
Aprotinin Blood loss and transfusions required are lowest with what dosing?
with full dose regimen
54
Aprotinin Allergic reactions caused by? | found in peds when?
-Foreign protein from bovine source -Size similar to protamine -1st time exposure reaction rare -Found reaction in kids with less than 6 months between exposures ›FDA revised advisory to put 12 months between exposures
55
Aprotinin how to test dose for an allergic reaction?
-Test dose of 1mL given prior to loading dose -Wait about 10 min after test dose before starting loading dose
56
Aprotinin effects what substances? (8)
``` Non-specific serine protease inhibitor Effects: ›Trypsin ›Chymotrypsin ›Plasmin ›Kallikrein !!!! (Know this one) ›Bradykinin ›TPA ›Urokinase Plasminogen Activator ›Complement ```
57
Kallikrein does what?
``` >Decrease inflammation >Doesn’t affect bleeding ›DOES activate intrinsic cascade ›Activation of coagulation precursor proteins ›Activates pro-inflammatory WBCs ›Inhibits Platelet-WBC Interactions ```
58
Are TA and ACA FDA approved for prophylactic use in cardiac surgery?
NO
59
Aprotinin - FDA Revised labeling (2006)
Don’t give w/in 12 mo of prior exposure ›Only for patients who are at increased risk for blood loss and blood transfusion associated with CPB in the course of a CABG
60
Recombinant Factor VIIa cost?
$5,000-$9,000 /dose | May require multiple doses
61
Aprotinin competes with what in the Acending Loop of Henle?
COmpetes with creatinine in the ascending Loop of Henle. ›Expect the rise in creatinine with Aprotinin > this does not mean there is necessarily renal damage
62
What is the cheapest? ACA, TA or Aprotinin?
``` ACA < TA < Aprotinin --ACA–generic›$1.50-$10 per 5gm vial ›Case: $5-$30 --TA–generic›Case: $20-$300 --Aprotinin–off patent, but costly to extract›$300-$450 per bottle ›Case: $1000-$1500 ```
63
In 2008 what happened to Aprotinin ?
Permanently withdrawn from the market ›Use is limited to very select research
64
Retrospective studies associate Aprotinin with: (adverse side effects {4])
- Renal Failure - Stroke - MI - Increased Mortality * *NOT seen with Lysine Analogs
65
How to avoid post op bleeding - in general?
-Rewarm the patient thoroughly -Reverse Protamine -Get all the surgical bleeders -Be aware of hemodilution -Consider use of antifibrinolytic/ lysine analog

Perf Tech II (exam 2) (6 decks)

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