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Perf tech II > test 8 > Flashcards

test 8 Flashcards

1
Q

Alterations to Coagulation on CPB

A 
-ž Heparinization
        › Neutralized by protamine
        › Some may be protein bound
ž- Excess Protamine
- Hemodilution
        › Appx 25-35% decrease in circulating factors
ž- Hypothermia
        › Slows enzymatic reaction times
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2
Q

Sources of Post-Op bleeding

A

ž- Reduced concentration of coagulation factors
ž- Hyperfibrinolysis
ž- Thrombocytopenia (decreased platelets)
ž- Impaired Platelet Aggregation
-ž Platelet Fragmentation
ž- Increased inflammation after CPB impairs coagulation and increases blood loss.

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3
Q

Extrinsic Factors

A

-ž Residual Heparin / Heparin Rebound
ž- Excessive Protamine
ž- Hemodilution
ž- Hypothermia

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4
Q

Prevention of Post-Op bleeding

A

-ž Avoiding CPB
ž- Improved biocompatibility of foreign surfaces (coated circuits)
ž- Alter conduct of bypass
› Drug doses, hypothermia, hemodilution
-ž Use hematologic strategies
› Take off blood before bypass and give it at the end
-ž Improved surgical technique!!!!!*
-ž Making sure labs are normal pre-op

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5
Q

Antifibrinolytic agents

A
  • stops breakdown of clot
    -ž CPB activates the breakdown of fibrinogen and other procoagulant precursors AND TRY TO MAKE US CLOT
    -ž ECC initiates contact activation
    -induces thrombin generation
  • Heparin has mild fibrinolytic effect
    › Stimulates release of serum urokinase plasminogen activator (UPA) which induces fibrinolysis
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6
Q

Tissue Plasminogen Activator (tPA)

A
  • Breaks down clots
    -ž More potent than UPA.
    -ž Primary activator of fibrinolysis during heart surgery.
    ž- Large surge of tPA after protamine is given
    › Time of greatest response to thrombin produciton
    -ž NO tPA = result in massive clots or DIC (Disseminated intravascular coagulation)
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7
Q

Trombin

A

-ž Produced throughout CPB
ž- Surge @ termination of bypass
ž- Surge after protamine administration
-ž Amplifier protein which activates inflammation, coagulation, and fibrinolysis
-ž Metabolically active in sites where heparin cannot reach it which results in clotting in these portions

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8
Q

Plasminogen Activator Inhibitor 1 (PAI-1)

A
  • Tries to stop tPA
  • Released by vascular endothelium and smooth muscle cells and find the tPA and bind to it
    › Therefore, tPA must overcome circulating PAI-1 to initiate fibrinolysis
    -ž PAI-1 is released in response to inflammatory mediators
    -ž PAI-1 is Prothrombic
    › Overcomes and suppresses fibrinolytic effect
    of tPA
  • Hemostasis = thrombin makes clot and tPA breaks down clot and PAI-1 prevents tPA from breaking down clots
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9
Q

tPA and post op bleeding

A

ž tPA directly cleaves plasminogen -> Plasmin => exposing a lysing binding site where fibrinogen and fibrin bind
-ž Fibrin is needed to crosslink platelets to make a clot
› TPA breaks apart fibrin and therefore, the clot
› Leads to post-op bleeding

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10
Q

Lysing Analogs to prevent post op bleeding

A

› Aminocaproic Acid (ACA) / Amicar

› Tranexamic Acid (TA)

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11
Q

Aminocaproic Acid (ACA) / Amicar

A

-ž 2 lysine molecules stuck together
-ž Competitively binds to lysine sites of plasminogen/ plasmin
› Prevents plasmin from binding to fibrinogen/ fibrin which PRESERVES FIBRIN => still have coagulation factors at the end

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12
Q

Tranexamic Acid (TA)

A
  • Reversibly binds to lysine receptors on plasminogen or plasmin.
    -ž Roughly 10 times the antifibrinolytic activity of ACA.
    › More potent
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13
Q

Aprotinin

A

-ž 58 amino acid polypeptide
-ž Single Lysine with a HIGH affinity for plasmin
-ž Non-specific serine protease inhibitor
› Inhibits fibrinolyis
› Inhibits thrombin generation
› Inhibits the inflammatory response

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14
Q

When to give lysine analogs

A
  • giving it before you go on bypass after heparin was the safest time to give this
  • ž Showed effective in decreasing blood loss.
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15
Q

Lysine analogs pharmacology

A

-ž IV Administration
ž- Uptake is immediate
ž- Small, water-soluble molecules
ž- Distributed readily into extravascular water spaced before being taken up into various cells and tissues.
- TA does bond weakly with protein so it can cross the BBB so don’t use in pregnant patients => USE AMICAR

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16
Q

Lysine analogs elimination

A

-ž Renal excretion

ž- Half-life: 1-2 hours with IV administration

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17
Q

Daily Protocol of ACA

A
  • (aka: “10-10-10”)
    › 10g given as slow bolus (5-10min) pre-CPB
    › 10g in CPB prime
    › 10g after CPB
    -ž Pt with kidney disease because it’s excreted with the kidneys
    -smaller loading dose
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18
Q

dosing of TA vs ACA

A

-the dose of TA is much smaller because it is more potent (1/7 to 1/10 of ACA)

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19
Q

Lysing analogs side effects

A

› Intravascular Clots in DIC patients

-ž Thromboembolic Complications

20
Q

Patients with low risk of transfusion (despite CPB)

A
  • may not benefit from prophylactic antifibrinolytics.
    But may help tip the scales between transfusion or not if they are on the fence.
  • but in pts that are really sick these drugs can tip the scales between transfusions and no transfusions
21
Q

Aprotinin

A
  • ž Found in all mammalian lung tissue
  • ž Isolated from bovine lung
  • single lysine binding site where it binds to plasmin and competitively hopefully inhibit fibrin binding
22
Q

Aprotinin pharmacology

A

-ž Full Hammersmith Regimen (Most common)
› 2 million iallokrein inhibing units (KIU) in pump
› 2 million KIU to pt over 30-60 minutes
› 500,000 KIU/hr infusion for pump run
› T1/2= 5 hours with this regimen
› Renal excretion (excreted via the kidneys)
› Blood loss and transfusions required are lowest with full dose regimen

23
Q

Aprotinin allergic reactions

A

-ž Foreign protein from bovine source
-ž Size similar to protamine
-ž 1st time exposure reaction rare
-ž Test dose of 1mL given prior to loading dose
-ž Wait about 10 min after test dose before starting loading dose
-ž Found reaction in kids with less than 6 months between exposures
› FDA revised advisory to put 12 months between
exposures.

24
Q

Aprotinin action

A

-ž Non-specific serine protease inhibitor
- Effects: (everywhere)
› Plasmin
› Kallikrein
› Bradykinin
› TPA
› Urokinase Plasminogen Activator
› Complement

25
Q

Aprotinin history

A

-ž Used/known since 1960s
-did not have an effect on Pulmonary gas exchange and post op lung dysfunction
- The surgical field was dramatically DRY.
› Lead to the early publications of transfusion sparing and decrease chest tube drainage associated with Aprotinin.
› Aprotinin may have neurologic protective effects (perfect for old people and circ arrest)
- A LOT LESS BLOOD LOSS

26
Q

Aprotinin dosing

A

-ž Came up with a formula they thought would drastically inhibit kallikrein production
› 2 million KIU pre-CPB
› 2 million KIU in pump
› 500,000 KIU/hr to cover metabolism/ clearance

27
Q

So what does aprotinin do?

A

-ž Decreasing Kallikrein
› Decrease inflammation
- Kallikrein doesn’t affect bleeding
› DOES activate intrinsic cascade
› Activation of coagulation precursor proteins
› Activates pro-inflammatory WBCs
› Inhibits Platelet-WBC Interactions
-ž Inflammatory down regulation by protecting platelets

28
Q

Aprotinin ability to produce desired results

A

-ž Decreased chest tube output (bleeding)
› 30% reduction in blood transfusions
› Less chest tube drainage
› Reduction in reoperations for bleeding
› 40-80% reduction in chest tube output compared to placebo

29
Q

Aprotinin issues

A
  • use creatinin as an indicator of renal function
  • body is trying to clear creatinin and aprotinin and they both are competing for clearance => levels increase for a period of time
30
Q

Kidney function and risk for dialysis

A
  • ž Normal GFR – Low risk for dialysis
  • ž 50% Normal GFR - >20% risk for dialysis
  • ž <20% Normal GFR – 85% risk for dialysis
31
Q

Aprotinin and clearance by the kidneys

A

-ž Aprotinin competes with creatinine in the ascending Loop of Henle.
› Expect the rise in creatinine with Aprotinin

32
Q

Mangono study

A

› Increased risk of:

     - Renal failure
     - MI
     - Heart Failure
     - Stroke
     - Encephalopathy
     - Increased mortality
33
Q

Comparing aprotinin to ACA, TA, and no antifibrinolytic

A

-ž Found that the use of Aprotinin was associated with an increased risk of renal and non-renal events compared to ACA, TA, and no antifibrinolytic
› Risk increases as the dose increases

34
Q

ACA cost

A

› $1.50-$10 per 5gm vial

› Case: $5-$30

35
Q

TA cost

A

› Case: $20-$300

36
Q

Aprotinin cost

A

› $300-$450 per bottle

› Case: $1000-$1500

37
Q

If ACA or TA given, you might need to give something for clotting issues

A

› Recombinant Factor VIIa - $5,000-$9,000 / dose
› RBC: $300-$500
› Platelets: $850
› FFP: $100

38
Q

What surgery was aprotinin approved for?

A

› Aprotinin was only approved for use on CABG surgery patients
- BUT high risk non-CABG patients had best benefit

39
Q

Aprotinin downfall: December 2006 – FDA Revised labeling

A

› 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

40
Q

Aprotinin downfall: 2007

A
  • Temporarily withdrawn from the market worldwide

- STS guidelines - high dose aprotinin for high risk patients

41
Q

Aprotinin downfall: 2008 (Bart study)

A 
- permanently withdrawn from the
market
› Lower bleeding than lysine analogs
› Significantly increased mortality
-ž Europe and North America  Temporarily suspended marketing authority for aprotinin.
42
Q

Aprotinin downfall: 2011

A
  • Health Canada lifted temporary marketing suspension
43
Q

Aprotinin downfall: 2012

A
  • European Medicines Agency recommended lifting suspension
44
Q

Complications of lysine analogs and aprotinin

A

› Intravascular Thrombis

› Aprotinin increases serum creatinine transiently

45
Q

Retrospective studies associate Aprotinin with:

A
  • Renal Failure
  • Stroke
  • MI
  • Increased Mortality
  • **NOT seen with Lysine Analogs
46
Q

Avoid post-op bleeding

A
  • ž Rewarm the patient thoroughly
  • ž Reverse Protamine
  • ž Get all the surgical bleeders
  • ž Be aware of hemodilution
  • ž Consider use of antifibrinolytic/ lysine analog

Perf tech II (16 decks)

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