Topic 15

Question 1

Protamine: is ______ and _____

Answer 1

positive and alkaline

Question 2

Heparin binds with Protamine in a 1:1 ratio, so for

every 100 units of heparin in a critter…

Answer 2

1 mg of protamine should effect heparin “reversal”

Question 3

This Heparin:Protamine complex does not effectively interact with

Answer 3

AT III, so the coagulation pathway/cascade proceeds unimpeded

Question 4

Protamine by itself is an anticoagulant: it decreases

Answer 4

thrombin generation by inhibiting Factor V activation

Question 5

Protamine is eliminated rapidly from

Answer 5

the plasma (faster than heparin) 
--so dosing protocols of 1.1:1.0 to 1.3:1.0 protamine:heparin have been developed

Question 6

Protamine is always given _______ with a very rapid (____ minutes) onset of action

Answer 6

parenterally

<5minutes

Question 7

Protamine has a median half-life of ______, compared to heparin’s median half-life of _____

Answer 7

~5 minutes

1-2 hours

Question 8

The metabolic fate of the protamine:heparin complex has not been completely elucidated. One possibility is that some of the complex is degraded by

Answer 8

fibrinolysin which would liberate free heparin

Question 9

“heparin rebound”.-Essentially, you give your dose of protamine, ACT’s (or whatever you’re using) normalize, and over time it appears that increased bleeding “happens”, often over the course of minutes to ~5 hours. Why?

Answer 9

1. “Free” heparin released from the protamine:heparin complex
2. Heparin’s variable half-life outlives protamine’s ~2 hour clinical effect?
3. Heparin from tissue stores?
4. Too much “reversal” protamine given (and given,
   and given, and given…)
5. Some data suggests heparin rebound may not really
   occur at all (Prolene deficiency?)

Question 10

Some studies suggest that smaller initial doses of protamine with well-regulated, well-calculated post-bolus infusions are a

Answer 10

more effective way to prevent post-op bleeding

Question 11

Protamine is also a component of ____ insulin

Answer 11

NPH

Question 12

Protamine- Only partially/unpredictably reverses

Answer 12

LMWH

Question 13

Protamine has no effect on

Answer 13

fondaparinux

Question 14

Protamine: Precautions & Problems

Answer 14

1. Protamine is an anticoagulant

2. Protamine reactions

Question 15

Contributing Factors to Protamine Reactions

Answer 15

1. Rapid administration

2. Sensitization to Protamine (Redo Surgeries, Fish allergies, Diabetics, Vasectomy, ”Excessive” dosage)

Question 16

Protamine Reactions Classically manifest themselves as

Answer 16

anaphylaxis &/ extreme hypotension,
pulmonary hypotension
cardiovascular collapse

Question 17

Protamine reactions: Often necessitates “crashing” back on CPB. *Minimized by:

Answer 17

Slow administration
Intra-aortic administration
Administration with steroids and antihistamines

Question 18

Vitamin K is to Warfarin as protamine is to

Answer 18

heparin

Question 19

Vitamin K: A fat soluble vitamin essential for the production of Factors

Answer 19

II, VII, IX, & X (2, 7, 9, 10)

Question 20

2 types of Vitamin K

Answer 20

K₁: Phytonadione (Mephyton) [veggies/supplements]

2) K₂: Menaquinone [Meat, poultry, eggs, butter, supplements]

Question 21

So, you’ve got a patient on a VAD… How, what, and why

does Vitamin K play a huge part in patient management & survivability???

Answer 21

vitamin K can prevent warfarin from working

Question 22

what type of vitamin K is the most “clinically” relevant form for perfusionists

Answer 22

K1

Question 23

dose of K₁ is given by injection for warfarin overdosage

Answer 23

1. 0-2.0 mg

- This dose will lower the PT but not completely eliminate the desirable warfarin effects

Question 24

Vitamin K MUST be given

Answer 24

slow IV (anaphylaxis is a common side effect).
•Requires at least six hours to be effective!

Question 25

Typical FFP dose for warfarin overactivity is

Answer 25

15ml/kg.

Question 26

Antifibrinolytics: drugs

Answer 26

``` Aminocaproic Acid (EACA) (Amicar) Tranexamic Acid (Cyklokapron, Lysteda) ```

Question 27

both Antifibrinolytics drugs are

Answer 27

synthetic derivatives of the amino acid lysine.

Question 28

Aminocaproic Acid

Answer 28

(Amicar)

Question 29

Tranexamic Acid

Answer 29

(Cyklokapron, Lysteda)

Question 30

Tranexamic is ____ times more potent than Aminocaproic Acid

Answer 30

10x

Question 31

Antifibrinolytics: Both drugs prevent plasminogen activation and directly inhibit plasmin which prevents

Answer 31

fibrinolysis

Question 32

Antifibrinolytics: Both significantly reduce post-bypass

Answer 32

hemorrhage, especially in patients who have received previous fibrinolytic therapy

Question 33

Antifibrinolytics: both are cleared

Answer 33

renally

Question 34

Antifibrinolytics: both commonly used in

Answer 34

pump primes (typically 10-15 g Amicar for example)

Question 35

Serine Protease Inhibitor: drug names

Answer 35

Aprotinin (Trasylol) | Desmopressin (DDAVP)

Question 36

Aprotinin

Answer 36

(Trasylol)

Question 37

Aprotinin blocks what

Answer 37

plasmin | - dramatically reduces post-op bleeding

Question 38

Desmopressin is a synthetic form of

Answer 38

Antidiuretic Hormone (ADH or Vasopressin), a small protein. •Much less pressor activity than Vasopressin

Question 39

Desmopressin causes the release of

Answer 39

von Willebrand’s Factor from vascular endothelium which increases Factor VIII and Factor XII activity

Question 40

Desmopressin is useful for

Answer 40

mild Hemophilia A and von Willebrand’s Disease

Question 41

Desmopressin: Causes platelets adhesiveness to increase in patients with

Answer 41

platelet dysfunction 2° to uremia or hepatic dysfunction

Question 42

***”Evidence-Based Note”: There is NO research that indicates the use of DDAVP for

Answer 42

bleeding post-bypass decreases the use of blood products (may be somewhat beneficial when administered in advance.)

Question 43

Blood Products: two types

Answer 43

Fresh Frozen Plasma (FFP) | Cryoprecipitate (Cryo)

Question 44

Fresh Frozen Plasma=

Answer 44

Plasma is separated from whole blood and stored at < 0 degrees Fahrenheit within eight hours of donation

Question 45

FFP’s use has skyrocketed...often given for

Answer 45

bleeding” post-bypass

Question 46

FFP is Preferably given with

Answer 46

ABO cross-matching

Question 47

FFP contains

Answer 47

Factors I, II, V, VII, IX, X, XI, XIII (1, 2, 5, 7, 9, 10, 11, 13) AT-III proteins C & S

Question 48

FFP is used for: (5)

Answer 48

``` “bleeding” immediate warfarin reversals AT-III deficiency with large volumes of PRBC administration colloidal volume replacement ```

Question 49

_____ of FFP raises a patient’s AT III levels by ___%

Answer 49

20ml/kg | ~20%.

Question 50

Cryoprecipitate: Derived from the precipitate that forms after

Answer 50

FFP is thawed and centrifuged

Question 51

Cryoprecipitate: Usually given as a “pooled” ( ___ units) product but ABO cross-matching is considered desirable. (A single Cryo unit is virtually never given!)

Answer 51

4-6 units

Question 52

Cryoprecipitate is used for ___, ____ and ___ replacement

Answer 52

Factor I, VIII, and von Willebrand’s --BUT, levels of VIII and VWF are “iffy” and cryo is NOT treated in any way whatsoever to decrease the risk of viral exposure!!!

Question 53

Cryo dose

Answer 53

1 unit = 15 ml | 15 ml ~250-350mg fibrinogen