Exam 3: Antifibrinolytics, Protamine, DDAVP (pro-clotting things) Flashcards
1
Q
antifibrinolytic meds: what do they do?
A
- we don’t want the clot to break down - think of spine surgeries!
- prevents the lysis of fibrin - promotes clot formation
- clot can now be stable!
- used to prevent and treat excessive bldg as inhibitors of fibrinolysis
- interfere with the formation of fibrinolytic enzyme plasmin from its precursor plasminogen by plasminogen activators (primarily t-PA and u-PA) which takes place mainly in lysine-rich areas on the surface of fibrin
- competitive inhbiition of plasminogen conversion to plasmin
2
Q
antifibrinolytic meds: what are the 2 types?
A
- lysine analogs
- Tranexamic Acid (Cyklokapron, Lysteda)
- Aminocaproic acid (Amicar)
- serine protease inhibitor (aprotinin - no longer avail)
3
Q
Steps from Epithelial injury to hemorrhage, and where lysine analogs (tranexamic acid and Amicar) and serine protease inhibitros (aprotinin) work
A
Epithelial injury
↓
plasminogen
↓ (tranexamic acid works here)
Plasmin (aprotinin works here)
↓
Fibrinolysis
↓
Hemorrhage
4
Q
Epsilon Ainocaproic Acid (Amicar):
MOA
Uses
dosing range
A
- FDA-approved for use in the tx fo acute bldg d/t elevated fibrinolytic activity
- inhibits the proteolytic enzyme plasmin, the enzyme responsible for fibrinolysis
- clinical uses include
- trauma
- CPB
- spinal fusions
- Dosing
- bolus: 5-15 g (peds 75-150 mg/kg)
- gtt: 1-2 g/hr (peds 5-30 mg/kg/hr)
5
Q
TXA - Tranexamic acid (cylokapron)
A
- will see this more often
- a synthetic analog of the aa lysine. inhibits fibrinolysis by competitively binding to the lysine receptor sites on plasminogen. This prevents plasmin from binding to and degrading fibrin (which preserves the fibrin matrix structure)
- parenteral TXA is effective in tx bldg from multiple causes such as GI, surgical, and trauma
- T1/2: ~ 2 hrs
- 8-10x more potent thatn aminocaproic acid!
- ortho cases: will bolus at the beginning, and then re-dose at the end of the case
- spine case that might be 6-10 hrs: gtt
6
Q
TXA: dosage and clinical uses (5 categories)
A
- Dosage
- 10-15 mg/kg IV (up to 1 g) followed by an infusions of 1-5 mg/kg/hr
- Duke’s dosage
- 1 g = about $50
- 10-15 mg/kg IV (up to 1 g) followed by an infusions of 1-5 mg/kg/hr
- Clinical uses
-
non-cerebral trauma
- suggested to only be beneficial within the 1st 3 hrs
- Peds
- spine fusions, craniosynostosis
- Ortho
- joint proced’s
-
Obstetrics
- massive transfusion algorithms
-
non-cerebral trauma
7
Q
(No question, just look at this image)
A
8
Q
CRASH-2 Trial
A
- TXA = CRASH-2 Trial
- 20,011 adults with traumatic bldg and showed that tranexamic acid reduces death d/t bldg with no increase in vascular occlusive events
- fucking wow.
- Strong evidence of a time to treatment
- in pts tx’d within 3 hrs of injury, TXA reduced death d/t bleeding by 1/3, but when given after 3 hrs, it seemed to increase risk (not sure why)
9
Q
TXA in PPH
A
- PPH is the leading cause fo maternal deaths worldwide
- 14/100,000 US
- compare to Sierra Leone >1000/100,000
- Early admin of TXA reduces bldg in trauma
- WOMAN (World Maternal Antifibrinolytic) Trial Lancet 2017
- women 16+, 193 hospitals, 21 countries - diagnosed with PPH
- PPH = >500 mL for vaginal delivery, or >1000 mL for C-sxn
- March 2010-April 2016, 20,060 women were enrolled and randomly assigned to get TXA vs placebo
- Death d/t bleeding was significantly reduced in women given TXA, esp if women given tx within 3 hrs of giving birth (~1/3) wiht no significant increase/decrease in any other cause of death
- Basically, same as CRASH-2.
10
Q
TXA contraindications and precautions
A
This is important for us to remember bc we’re the one who needs to catch it bc the TXA might be on a standard drug order sheet but the pt has a contraindication!
- Contraindications
- active intravascular clotting (PE, DVT, embolic cerebral stroke)
- will worsen clotting, or stabilize that clot!
- anaphylaxis
- SAH - associated with cerebral infarction
- active intravascular clotting (PE, DVT, embolic cerebral stroke)
- Precautions
- eliminated unchanged in the urine - requires decreased dosing in pts with renal impairment
- ex: max dosing of initial dose will now be 0.5 g instead of 1 g
- UTI - ureteral obstructions d/t clot formation has been reported
- think about it ≅ to septic pt, narrower tube, and there’s inflammation there, and TXA will want to clot in that area and now you have an obstruction
- hypotension with rapid IV injection
- color vision defect - visual changes are an indicator of toxicity
- one of the 1st signs of toxicity
- …but won’t see this with anesthetized pts
- sz disorders (1.3-3.8% - risk of sz’s is associated with high doses)
- might affect the GABA receptor in the brain?
- concomitant admin with factor concentrates
- makes sense - tipping the scale for them wanting to clot
- eliminated unchanged in the urine - requires decreased dosing in pts with renal impairment
11
Q
Creator of TXA
A
Utako Okamoto and her husband
12
Q
Protamine ***
(know for the rest of your life)
A
- when you start cardiac, preceptors love pimping you on protamine
- protamine (protamines) are simple proteins obtained from the sperm of salmon and certain other species of fish
- the positively charged alkaline protamine combines with the negatively charged acidic heparin to form a stable complex void of anticoagulant activity
- Heparin-Protamine compex is removed by the reticuloendothelial system
13
Q
Protamine: Dose and Adverse responses (3)
A
- dose
- 1-1.5 mg for every 100 units of heparin that were given
- guided by last ACT and estimated amt of total IV heparin admin within the last 2 hrs
- (not really going to dose on ALL the heparin that you gave)
- Adverse Responses
- Hypotension
- rapid IV injection = histamine release (hypotension, facial flushing, tachycardia)
- pHTN
- protamine-heparin complex can result in complement activation and thromboxane release = pulmonary constriction
- allergic rxns
- Hypotension
- really just start with what was given in the last 2 hrs, and go from there
- ALSO need to think about if you even want to reverse ALL the heparin. Just want to get it <200 so that they can pull a sheath. Vs they might want some of that ac effect of heparin if they put in a
14
Q
chart guide for protamine dosing based on time since last dose of heparin:
immediate/just given
30 min-2 hrs (since last heparin given)
> 2 hrs
A
just given: 1 mg/100 units heparin (or 25 mg fixed dose)
30m-2 hrs: 0.5 mg/100 units heparin (or 10 mg fixed dose)
>2 hrs: 0.25 mg/100 units heparin (or 10 mg fixed dose)
15
Q
Allergic rxns to protamine
A
- options are limited for use in pts with a true allergy to protamine!
- pretx with histamine receptor antagonist (benadryl), followed by a slow trial
- completely avoid protamine, and allow heparin effect to dissipate
- but takes hrs, risk for bleeding and blood transfusions
- admin alternative to heparin
- limited - e.g. Bivalirudin
