Anticoagulants Flashcards
Warfarin elimination 1/2 life:
24-36 hrs
warfarin reversal
Vitamin K, PCCs for immediate reversal but availability issues(?); FFP (transfusion risk and volume concerns)
Dextran MOA
binds to platelets and causes inhibited function
ASA MOA
o IRREVERSIBLY inhibits cyclooxygenase –>thromboxane A2 (7-10 days)
Thrombolytics
Streptokinase, urokinase, tissue plasminogen activator (tPA) (Alteplase®)
Thrombolytics MOA
Activates plasminogen to plasmin & causes clot breakdown
Antifibrinolytics MOA
Block conversion of plasminogen to plasmin & causes inhibited clot lysis
Antifibrinolytics
Tranexamic acid (TXA) & aminocaproic acid (Amicar®):
Aprotinin MOA
Protease inhibitor & causes plasmin inhibition
TXA studies:
decrease blood loss and blood products; no increase risk of unwanted thrombi
Initiation Phase (Extrinsic)
Vessel damage
-> tissue factor (TF) release which binds with VIIa
-> conversion of X to Xa
->small amount of thrombin
Amplification Phase (intrinsic):
Plts, V & XI activated by thrombin
Propagation Phase
VIII, IX and calcium on plts ->activation of X
while
thrombin activates plts, V, VIII -> VIIIa-IXa complex
->The VIIIa-IXa complex switches reaction to intrinsic tenase (Xase) pathway -> 50 x more efficient at Xa generation.
->So increased Xa -> large amount of thrombin
heparin onset IV
immediate
unfractionated heparin MOA
Binds to antithrombin _ enhanced binding with thrombin
heparin unit?
1U = volume that prevents 1 mL blood from clotting for 1 hr after combining with Ca++
heparin onset sub-cu
1-2 hr
heparin aPTT range
1.5 - 2.5 x Normal (N=30-35 sec)
low dose heparin monitored with
anti-Xa assay
high dose heparin monitored
ACT > 350 – 400 sec (affected by hypothermia and hemodilution)
HIT severe
plt ct <100,000 (or 50% drop)
HIT associated w/ thrombus after
4-5 days of treatment
heparin reversal
protamine - 1 mg for each 100 U circulating heparin
warfarin onset
predictable but delayed 8-12 hrs
warfarin peak
36-72 hrs, but may take up to 5 days
warfarin INR
“Moderate anticoagulation” = INR of 2.0 - 3.0
warfarin monitor INR peri-op
d/c 1-3 days pre-op, reinstitute 1-7 days post op, use UFH to bridge high risk clotters
protamine clearance
20 mins (risk of heparin rebound)
heparin clearance 1/2 life:
1 hr
DVT occurs in what percent of gen. surgery?
10-40%, increased with higher acuity
PE occurs in?
2 – 22% of traumas. PE is common cause of death after first 24 hours post-trauma.
VTE prophylaxis
- Heparin
- LMWH (enoxaparin, dalteparin)
- Xa inhibitors (fondaparinux, rivaroxaban)
- Thrombin inhibitors (dabigatran, argatroban)
NOAC - Direct thrombin inhibitors:
dabigatran (Pradaxa®)
bivalirudin (Angiomax®)
argatroban (Arcova®)
NOAC - Direct Xa inhibitors:
rivaroxaban (Xarelto®)
apixaban (Eliquis®)
fondaparinux (Arixtra®)
low risk blood loss on NOACs
D/C 24 hrs pre-op, resume 24 hrs post-op
moderate/high risk blood loss on NOACs
D/C 5 days pre-op, resume when risk of bleeding drops
elective procedures on NOACs
Bridging probably not required; consider patient-specific risk/benefits
ER procedures while on NOACs
Delay as long as possible; do not prophylax with recombinant VIIa (Novo 7®) or PCCs.
Life-threatening hemorrhage while on NOACs
Consider recombinant VIIa or PCCs.
best testing for NOACs
aPTT and TT
Thienopyridines MOA
Binds to P2Y12 receptor–>inhibits platelet activation and aggregation
Thienopyridines
Clopidogrel (Plavix®)
Prasugrel (Effient®)
Ticagrelor (Brilinta®)
Dipyridamole (Persantine®) MOA
increase cyclic AMP causes decrease plt function
Platelet glycoprotein IIb/IIIa antagonists
abciximab (ReoPro®);
tirofiban (Aggrastat®);
eptifibatide (Integrilin®)
glycoprotein IIb/IIIa antagonists MOA
Bind or inhibit fibrinogen receptor - causes decrease in plt aggregation
peri-op recommendations for thienopyridines
D/C 7 days pre-op, avoid neuraxials until drug effects cleared
When must TXA be administered?
during first 3 post-injury hours
TXA in non-trauma surgery dose
15 mg/kg IV infusion (most efficacious) or
1g is common (regardless of weight)
TXA FDA approved use?
-Heavy menstrual bleeding
-Short-term hemorrhage prevention with hemophilia
TXA off-label use?
- Elective c-sections and PP bleeding
- Total knee arthroplasty
- Orthognathic and craniofacial surgery
- Cardiac surgery
- Spinal surgery
- (TURP)
- Non-traumatic subarachnoid hemorrhage
- GI bleeding
TXA protocol
- 1 gm preoperatively in holding
- Additional 1 gm during closing
contraindications for TXA
-Hypersensitivity to antifibinolytics
-Acquired color vision deficit
-Caution with renal impairment
-Caution with thrombus history
when does heparin rebound usually occur
2-3 hours post protamine
adverse reactions of protamine
- Anaphylaxis, pulmonary vasoconstriction with RV failure, hypotension
- ↑ risk with NPH insulin, vasectomy, prior protamine, drug allergies
Desmopressin (DDAVP) treats?
- Mild hemophilia A, von Willebrand’s dz, cardiac surgery(?)
- infuse slowly to avoid hypotension
Normal Fibrinogen
200-400 mg/dL
Fibrinogen in pregnancy
> 400 mg/dL
what is used to treat low fibrinogen?
cryoprecipitate or fibrinogen concentrates (can be refractory to FFP)
what indicates low fibrinogen?
elevated PT and PTT
Recombinant Factor VIIa (NovoSeven®) use?
For hemophilia;
off-label use for life-threatening hemorrhage & CV surgery
Factor VIIa (NovoSeven®) cost?
$1,000/mg; average pt: 70 kg ;
average dose: $7,000 (100 mcg/kg = 7000 mcg or 7 mg)
Factor VIIa (NovoSeven®) average treatment?
Dose every 2-3 hours until hemostasis achieved
Prothrombin Complex Concentrates (PCCs) treats?
Warfarin reversal, hemophilia B, various off-labels
In U.S. what is commonly used for warfarin reversal versus other countries?
U.S. uses FFP and other countries use more PCCs
PCCs are primary treatment for what?
hemorrhage with ↑ INR when urgent reversal needed
Compared to FFP, PCCs are?
faster reversal, less volume, no cross-matching
