Antifibrinolytics, Protamine, and DDVAP

Question 1

What is the purpose of antifibrinolytic medications?

Answer 1

prevents the lysis of fibrin
used to prevent and treat excessive bleeding as inhibitors of fibrinolysis
interfere with the formation by plasminogen activators (primarily t-PA and u-PA which takes place mainly in lysine rich areas on the surface of fibrin

Question 2

Two types of competitive inhibition of plasminogen conversion to plasmin are

Answer 2

lysine analogs (txa and amicar)
serine protease inhibitor (aprotinin)

Question 3

Epsilon Aminocaproic Acid (amicar)

Answer 3

fda approved for use in the treatment of acute bleeding due to elevated fibrinolytic activity
inhibits the proteolytic enzyme plasmin, the enzyme responsible for fibrinolysis

Question 4

Clinical uses of amicar

Answer 4

trauma, CPB, and spinal fusions

Question 5

Dosing ranges of amicar

Answer 5

bolus: 5-15g (peds 75-150mg/kg)
infusion: 1-2 g/hr (peds 5-30mg/kg/hr)

Question 6

Txa tranexamic Acid (cylokapron)

Answer 6

a synthetic analog of the amino acid lysine
inhibits fibrinolysis by competitvely binding to the lysine receptor sites on plasminogen
prevents plasmin from binding to and degrading fibrin which preserves the fibrin matrix structure

Question 7

Parenteral TXA is

Answer 7

effective in treating bleeding from multiple causes such as GI , surgical and trauma

Question 8

Half life of TXA is

Answer 8

2 hours

Question 9

Which drug is more potent? AMinocaproic acid or TXA?

Answer 9

TXA by 8-10 times

Question 10

Clinical uses of TXA

Answer 10

non-cerebral trauma
peds- spinal fusions, craniosynostosis
orthopedic procedures
cardiac
obsterics (massive transfusion)

Question 11

Doses of TXA

Answer 11

10-15mg/kg IV (up to 1 gm) Following by an infusion of 1-5mg/kg/hr
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Question 12

CRASH-2 Trial

Answer 12

adults with traumatic bleeding showed that TXA reduces death due to bleeding wiht no increase in vascular occlusive events
patients treated within 3 hours of injury, TXA reduced death due to bleeding by 1/3 but after 3 hours increased risk of bleeding

Question 13

TXA in Post Partum Hemorrhage

Answer 13

20,060 woman enrolled in study
death due to bleeding was significantly reduced in woman given TXA especially woman treated within 3 hours of giving birth (nearly 1/3) with no significant increase or decrease in any other cause of death

Question 14

TXA contraindications

Answer 14

active intravascular clotting (pulmonary embolism, DVT, embolic cerebral stroke)
anaphlaxis
subarachnoid hemorrhage-associated with cerebral infarction

Question 15

TXA precautions

Answer 15

eliminated unchanged in the urine- requires decreased dosing in patients with renal function impairment
UTI d/t clot formation
hypotension with rapid IV injection
color vision defect- visual changes in an indicator of toxicity
seizure disorders
concomitant administration with factor concentrates

Question 16

Protamine

Answer 16

positively charged alkaline protamine combines with negatively charged acidic heparin to form a stable complex void of anticoagulant activity
heparin protamine complex is removed by reticuloendothelial system

Question 17

Protamine administration

Answer 17

1-1.5mg for every 100 units of heparin

guided also by the last ACT and estimated amount of total IV heparin administered in the last 2 hours

Question 18

Adverse Protamine Responses

Answer 18

hypotension (d/t histamine release)
pulmonary HTN (d/t heparin complex that can result in complement activation and thromboxane release= pulmonary constriction
allergic reactions

Question 19

What has the highest risk for a patient have a true allergy to protamine?

Answer 19

prior reaction to protamine (189x)
allergy to true (vertebrae fish) 24.5x
exposure to NPH insulin 8.2x
allergy to any drug 3x
prior exposure to protamine n/a

Question 20

DDVAP means

Answer 20

d-amino d arginine vasopresin (synthetic analogue of teh natural hormone arginine vasopressin)

Question 21

DDVAP

Answer 21

causes release of endogenous store of FVIII and von willebrand

Question 22

DDVAP dose

Answer 22

0.3mcg/kg IV infusion over 15-30 min

platelet adhesion increases within 30 minutes

Question 23

Pharmacology of DDVAP

Answer 23

has been shown to more potent than arginine vasopressin in increasign plasma levels of factor VIII activity in patients with von willebrand’s disease
the change in structure of arginine vasopressin to DDVAP results in decreased antidiuretic and vasopressor action on smooth muscle
excreted in urine
hypotension most reported side effect

Question 24

Contraindications to DDVAP

Answer 24

hypersensitivity
patients with moderate to severe renal impairment
patients with hyponatremia

Question 25

Desmopressin

Answer 25

is a synthetic analog of natural antidiurteic hormone vasopressin
its overuse can lead to h20 retention and dilutional hyponatremia with consequent convulsion
rare cases of the antidiuretic effects leading to water intoxication/hyponatremia which can be fatal

Question 26

TXA is

Answer 26

an antifibrinolytic and leads to a reduced bleeding rate

Question 27

Protamine binds to

Answer 27

heparin to create a complex void of anticoagulant activity

Question 28

Desmopressin

Answer 28

used to improve platelet function by releasing endogenous vWF