Antifibrinolytics, Protamine, DDAVP Flashcards
Antifibrinolytics types
- lysine analogs (tranexamic acid, aminocaproic acid)
- serin protease inhibitors (aprotinin)
Antifibrinolytics MOA
- 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
Antifibrinolytic Lysine Analog drug
- Aminocaproic Acid (Amicar)
- Tranexamic Acid (TXA)
Aminocaproic Acid (Amicar) MOA
inhibits the proteolytic enzyme plasmin, enzyme responsible for fibrinolysis
Aminocaproic Acid (Amicar) dose
- 5-15g bolus followed by 1-2 g/hr infusion
- Peds dosing: 75-150 mg/kg bolus; 5-30 mg/kg/hr infusion
Aminocaproic Acid (Amicar) clinical uses
- treatment of acute bleeding due to elevated fibrinolytic activity
- trauma
- CPB
- spinal fusions
Tranexamic Acid (TXA) MOA
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
Tranexamic Acid (TXA) PK/PD
- E ½ approximately 2 hours
- eliminated unchanged in urine
Tranexamic Acid (TXA) dose
10-15 mg/kg IV (up to 1g), followed by 1-5 mg/kg/hr infusion
Tranexamic Acid (TXA) clinical uses
- GI bleeding
- surgical bleeding
- non-cerebral trauma
- pediatrics (spinal fusion, craniosynostosis)
- ortho procedures
- cardiac procedures (with or without CPB)
- obstetrics (MTP)
Tranexamic Acid (TXA) considerations
- 8-10 times more potent than Amicar
- CRASH 2 trial; traumatic bleeding, TXA reduces death if treated within 3 hours of injury
Tranexamic Acid (TXA) contraindications
- active intravascular clotting
- anaphylaxis
- SAH
Tranexamic Acid (TXA) precautions
- 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
Protamine MOA
- 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
Protamine dose
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)
Protamine adverse responses
- 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)
DDAVP (D-amino-D-arginine vasopressin)
Synthetic analogue of the natural hormone arginine vasopressin
DDAVP MOA
causes release of endogenous store of FVIII and von Willebrand
DDAVP PK/PD
- excreted by urine
- t ½ 3 hours in healthy patients and up to 9 hours in severe renal impairment
DDAVP dose
0.3 mcg/kg IV infusion over 15-30 min
DDAVP contraindications
- 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
patients at risk for true allergy to protamine
- 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
