Antifibrinolytics, Protamine, DDAVP

Question 1

Antifibrinolytics types

Answer 1

• lysine analogs (tranexamic acid, aminocaproic acid)

- serin protease inhibitors (aprotinin)

Question 2

Antifibrinolytics MOA

Answer 2

• prevent lysis of fibrin
• used to prevent and treat excessive bleeding as inhibitors of fibrinolysis
• interfere with formation of fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators, which takes place in lysine rich areas on surface of fibrin

Question 3

Antifibrinolytic Lysine Analog drug

Answer 3

• Aminocaproic Acid (Amicar)

- Tranexamic Acid (TXA)

Question 4

Aminocaproic Acid (Amicar) MOA

Answer 4

inhibits the proteolytic enzyme plasmin, enzyme responsible for fibrinolysis

Question 5

Aminocaproic Acid (Amicar) dose

Answer 5

• 5-15g bolus followed by 1-2 g/hr infusion

- Peds dosing: 75-150 mg/kg bolus; 5-30 mg/kg/hr infusion

Question 6

Aminocaproic Acid (Amicar) clinical uses

Answer 6

• treatment of acute bleeding due to elevated fibrinolytic activity
• trauma
• CPB
• spinal fusions

Question 7

Tranexamic Acid (TXA) MOA

Answer 7

inhibits fibrinolysis by competitively binding to the lysine receptor sites on plasminogen, preventing plasmin from binding to and degrading fibrin which preserves the fibrin matrix structure

Question 8

Tranexamic Acid (TXA) PK/PD

Answer 8

• E ½ approximately 2 hours

- eliminated unchanged in urine

Question 9

Tranexamic Acid (TXA) dose

Answer 9

10-15 mg/kg IV (up to 1g), followed by 1-5 mg/kg/hr infusion

Question 10

Tranexamic Acid (TXA) clinical uses

Answer 10

• GI bleeding
• surgical bleeding
• non-cerebral trauma
• pediatrics (spinal fusion, craniosynostosis)
• ortho procedures
• cardiac procedures (with or without CPB)
• obstetrics (MTP)

Question 11

Tranexamic Acid (TXA) considerations

Answer 11

• 8-10 times more potent than Amicar

- CRASH 2 trial; traumatic bleeding, TXA reduces death if treated within 3 hours of injury

Question 12

Tranexamic Acid (TXA) contraindications

Answer 12

• active intravascular clotting
• anaphylaxis
• SAH

Question 13

Tranexamic Acid (TXA) precautions

Answer 13

• decrease in patients with renal function impairment
• UTI (can cause ureteral obstruction)
• hypotension with rapid IV injection
• color vision defect
• seizure disorders
• concomitant admin with factor concentrates

Question 14

Protamine MOA

Answer 14

• simple protein obtained from sperm of salmon
• positively charged alkaline protamine combines with negatived charged acidic heparin to form stable complex void of anticoagulant activity
• heparin protamine complex removed by reticuloendothelial system

Question 15

Protamine dose

Answer 15

1-1.5 mg for every 100 units of heparin (guided also by last ACT and estimated amount of total IV heparin admin in last 2 hours)

Question 16

Protamine adverse responses

Answer 16

• hypotension (rapid IV injection = histamine release)
• pulmonary HTN (protamine heparin complex can result in complement activation and thromboxane release  pulmonary constriction)
• allergic reactions (pretreat with histamine antagonist or avoid)

Question 17

DDAVP (D-amino-D-arginine vasopressin)

Answer 17

Synthetic analogue of the natural hormone arginine vasopressin

Question 18

DDAVP MOA

Answer 18

causes release of endogenous store of FVIII and von Willebrand

Question 19

DDAVP PK/PD

Answer 19

• excreted by urine

- t ½ 3 hours in healthy patients and up to 9 hours in severe renal impairment

Question 20

DDAVP dose

Answer 20

0.3 mcg/kg IV infusion over 15-30 min

Question 21

DDAVP contraindications

Answer 21

• plt adhesion increases within 30 min
• shown to be more potent than arginine vasopressin in increasing plasma levels of factor VIII activity in patients with vWD
• hypotension is most commonly reported SE
• contraindications –> hypersensitivity, moderate to severe renal impairment, hyponatremia

Question 22

patients at risk for true allergy to protamine

Answer 22

• prior reaction to protamine
• allergy to true (vertebrate) fish
• exposure to NPH insulin [chronic exposure to low dose protamine may produce antibodies against protamine]
• allergy to any drug
• prior exposure to protamine