Anticoags|Procoags Flashcards
Vessel damage = tissue factor (TF) release which binds with VIIa = conversion of X to Xa = small amount of thrombin
Initiation Phase
Plts, V & XI activated by thrombin
Amplification 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
So increased Xa = large amount of thrombin
Propagation Phase:
this drug binds to antithrombin causing enhanced binding with thrombin which means?
heparin and if thrombin is bound..it is not available for clotting
uses of heparin?
prevent/treat thrombus PE coronary syndromes HD CP bypass
onset of subcu hep vs IV?
subcu 1-2 hours, IV immediate
what is heparin affected by?
temperature, protein binding, pt variable anticoagulation response, renal & hepatic disease
is heparin or LMWH [lovenox] more susceptible to temp, protein binding, renal/hepatic dz?
LMWH!
3 lab values that can be used to monitor heparin and when to choose which one?
Low dose xa high dose (bypass) ACT 350-400 aPTT
therapeutic range of aPTT on hep?
1.5 - 2.5 x NL (N=30-35 sec)
what is HIT
heparin induced thrombocytopenia
plt count <100,000 or 50% drop from baseline
MOA of HIT
heparin dependent antibodies trigger plt aggregation which causes thrombocytopenia
Reversal of heparin?
protamine - 1 mg for each 100 units circulation heparin
why do we overdose protamine?
protamine clearance is 20 min faster than heparin clearance (1/2 life 1 hr) so could run risk of heparin rebounding
UFH & LMWH ↑ risk of neuraxial hematoma especially with
especially with NSAIDs, platelet inhibitors
why is lmwh have more consistent pharmacokinetics and better bioavailability at lower doses
Less protein binding than heparin
2 things to be cautious with when using LMWH
renal dz and its not antagonized by protamine
Predictable onset (but delayed for 8-12 hrs) and duration, effective PO; requires lab monitoring, difficult to reverse, crosses placenta
Warfarin (Coumadin®)
elimination half-life warfarin?
24-36 hours
Warfarin (Coumadin®) affected by
diet, drugs, ETOH, age, liver disease
Monitoring warfarin is Best w PT but unreliable, what did we do to fix this
INR - moderate = 2-3
Major surgery mgmt of warfarin?
Monitor INR peri-op; D/C 1-3 days pre-op; reinstitute 1-7 days post-op; UFH bridging for high-risk clotters
Reversal of warfarin?
Vitamin K (takes days) PCCs for immediate reversal but availability issues FFP (transfusion risk and volume concerns)
some examples of Newer Oral Anticoagulants (NOACs)
direct thrombin inhibitors
Dabigatran (Pradaxa®), Bivalirudin (Angiomax®, Angiox®), Argatroban (Arcova®)
some examples of Newer Oral Anticoagulants (NOACs)
direct Xa inhibitors
Rivaroxaban (Xarelto®), Apixaban (Eliquis®), Fondaparinux (Arixtra®)
Advantages Newer Oral Anticoagulants (NOACs)
Rapid onset, therapeutic range within hours, no need for routine lab monitoring
disadvantages Newer Oral Anticoagulants (NOACs)
Needs adjusted dose with renal disease, no antagonists, unable to monitor w simple lab assays, ↑ inter-patient variability
common cause of death after first 24 hours post-trauma
PE
meds to use for VTE Prophylaxis
Heparin
LMWH (Enoxaparin, Dalteparin)
Xa inhibitors (Fondaparinux, Rivaroxaban)
Thrombin inhibitors (Dabigatran, Argatroban)
Low risk Peri-op management with NOACs
D/C 24 hrs pre-op, resume 24 hrs post-op
Peri-op management with NOACs Mod-high risk
D/C 5 days pre-op, resume when risk of bleeding drops
Peri-op management with NOACs Elective procedures
Bridging probably not required; consider patient-specific risk/benefits
Peri-op management with NOACs ER procedures
Delay as long as possible; do not prophylax w recombinant VIIa (Novo 7) or PCCs
when should you Consider recombinant VIIa or PCCs
Life-threatening hemorrhage
Monitoring NOACs
aPTT and TT
IRREVERSIBLY inhibits cyclooxygenase = thromboxane A2 (7-10 days)
aspirin
when can you resume aspirin therapy?
24 hrs postop without bleeding
Thienopyridines examples
Clopidogrel (Plavix®); Prasugrel (Effient®); Ticagrelor (Brilinta®)
Thienopyridines MOA?
Binds to P2Y12 receptor = inhibits platelet activation and aggregation
Dual antiplatelet therapy ex
Thienopyridine (Plavix) + ASA
Dipyridamole (Persantine®) MOA?
↑ cyclic AMP ↓ plt function
Dextran MOA
Binds to platelets = inhibited function
Platelet glycoprotein IIb/IIIa antagonists MOA
abciximab (ReoPro®); tirofiban (Aggrastat®); eptifibatide (Integrilin®)
Bind or inhibit fibrinogen receptor = ↓ plt aggregation
Peri-op recommendations
Thienopyridines
D/C 7 days pre-op, avoid neuraxials until drug effects cleared
: Risks/benefits must be individualized, especially with elective procedures
ALL antiplatelets
Thrombolytics examples?
Streptokinase, urokinase, tissue plasminogen activator (tPA) (Alteplase®)
Thrombolytics MOA
Activates plasminogen to plasmin = clot breakdown
Use: Emergent treatment of PE, CVA, acute MI without PCI availability
Thrombolytics
Risks thrombolytics?
Intracranial hemorrhage; angioedema (especially with ACE inhibitor)
Treatment of too much thrombolytics?
Cryoprecipitate and/or platelets
Block conversion of plasminogen to plasmin = inhibited clot lysis
[does not induce clotting, just prevents breakdown]
Tranexamic acid (TXA) & aminocaproic acid (Amicar®):
TXA Studies show
↓ blood loss, ↓ blood products; no ↑ risk of unwanted thrombi
TXA must be administered at
<3 hours post-injury
TXA reduces risk of death due to bleeding, regardless of the cause.”
CRASH-3 and WOMAN studies
Most efficacious dose TXA for non trauma patients?
15 mg/kg
Contraindications TXA?
Hypersensitivity to antifibrinolytics
Acquired color vision deficit
Caution with renal impairment
Caution with thrombus history
reactions include: Anaphylaxis, pulmonary vasoconstriction with RV failure, hypotension
Protamine
Adverse reactions increased with protamine in patients who
NPH insulin, vasectomy, prior protamine, drug allergies
Analog of vasopressin, stimulates endothelial von Willebrand factor
Desmopressin (DDAVP)
Desmopressin (DDAVP) uses?
Mild hemophilia A, von Willebrand’s dz, cardiac surgery(?)
Binding site for IIb/IIIa receptors on platelets
fibrinogen
normal fibrinogen level and with pregnancy?
200-400 mg/dL; during pregnancy: >400 mg/dL
Elevated PT and PTT d/t ↓ fibrinogen should be treated with
cryoprecipitate or fibrinogen concentrates (can be refractory to FFP)
For hemophilia; off-label use for life-threatening hemorrhage
VIIa + tissue factor = thrombin and amplified hemostasis
Off-label use in CV surgery
Recombinant Factor VIIa (NovoSeven®)
Kcentra®, Octaplex®, FEIBA VH®, Profilnine®, Bebulin VH®
Prothrombin Complex Concentrates (PCCs)
Primary treatment for hemorrhage with ↑ INR when urgent reversal needed
Prothrombin Complex Concentrates (PCCs)
Compared to FFP: PCCs =
faster reversal, less volume, no cross-matching