Anticoagulation I Dr. Covert Flashcards
Dr. Covert EXAM IV
What factors contribute to Thrombosis?
Virchow’s Triad
-Endothelial Injury
-Abnormal Blood flow (long travel)
-Hypercoagulability (contraceptives, pregnancy, cancer therapy)
What tests assess clotting disorders?
intrinsic: PTT (play table tennis - inside)
normal: 25-35 sec
extrinsic pathway: PT (play tennis - outside)
normal: 12 sec
Reasons for prophylactic anticoagulation therapy
Some risk of clot
-Immobility in hospitalized patients (some) changes in blood
Reasons for full-dose anticoagulation
Big Risk of clot:
-Atrial fibrillation: change in blood flow, risk of stroke
-Mechanical heart valves: platelets will stick to it, endothelial injury, change in blood flow
-certain clotting disorder: hypercoagulable state
Presence of clot:
-Deep vein thrombosis
-Pulmonary embolism
What are the available Anticoagulants and MOA?
MOA: inhibit clotting or deplete clotting factors
Drugs:
-Warfarin blocks the reduction of Vitamin K -> which is needed for the carboxylation of factors
-DOACS ( direct oral anticoagulants): like apixaban
-heparin
-enoxaparin (LMWH)
Indication for Anticoagulants
-DVT
-PE
-Atrial fibrillation
-red clot: fibrin rich
What is the MOA of Antiplatelets?
MOA: inhibit platelet aggregation
drugs: Aspirin, P2Y12 inhibitors (clopidogrelel, prasugrel, ticagrelor)
white clot: platelet-rich
Indication of Antiplateteltes
-prevents platelet clots, makes the blood slippier
Indication:
-Ischemic stroke (preventing platelet clot -> stroke)
-coronary artery disease (CAD)
-peripheral artery disease
What are the injectable Anticoagulants?
-Unfractionated Heparin (UFH)
-Enoxaparin (LMWH)
MOA Heparin
-Potentiates antithrombin III (ATII) activity à Inactivates thrombin (Factor II) MOA and Factor Xa
Onset and duration:
IV: immediately (quick ON, quick OFF - useful right before surgery to turn OFF the anti coag state for surgery)
SQ: 20-30 min, OFF: 1-2h
How is heparin cleared?
Reticuloendothelial system (binds to endothelial cells)
NOT hepatically or renally cleared
Which tests are used to assess the activity of heparin?
Therapeutic drug monitoring
-heparin works on the intrinsic pathway
-aPTT, anti-Xa
What are the side effects of heparin and how can it be reversed?
ADE: Heparin-induced-thrombocytopenia (immune cells activate platelet-clotting), bleeding
-reverse agent: Protamine
Heparin-induced-thrombocytopenia
-platelets release PF4
-PF4 binds to the long tail of heparin -> the body reacts and release IgG -> IgG binds to PF4/heparin-complex -> the complex binds to endothelial cells
-> causing release of tissue factor -> tissue factor increases thrombin generation -> CLOTTING
all platelets are bound to the complex, patients have low platelets but still activate the clotting cascade
Platelet level in patients with HIT
low platelets
-high risk of clotting
-HIT is diagnosed based on the 4T score (likelihood of HIT, Lexicomp calculator)
-> if at risk -> DC heparin/enoxaparin and change to argatroban (direct thrombin inhibitor)
MOA Enoxaparin (LMWH)
Lovenox
Potentiates ATIII activity; Inactivates Factor Xa more than Factor II due to the short tail
Onset and duration Enoxaparin
Onset: SQ 1-3h
Duration: SQ 5-8h
How is Enoxaparin cleared?
Renally eliminated
Which heparin to use in dialysis patients or patients with poor kidney function?
Heparin
Enoxaparin is cleared renally
if the patient’s kidney is fine, can we still give heparin???
Which test to assess enoxaparin activity?
Therapeutic drug monitoring
Anti-Xa
ADR and reversing agent of enoxaparin
-less risk for heparin-induced-thrombocytopenia, bleeding
-reversing agent: Protamin
-> if patient is excessively bleeding, vomit blood, blood in stool
Prophylactic dosing Enoxaparin and heparin
Heparin: 5000 u SQ TID
Enoxaparin:
40 mg SQ daily
if BMI over 40: 40 mg SQ BID
if CrCl < 30 mL/min: 30 mg SQ daily
Full-dose Anticoagulation
-Heparin: 80 units/kg IV X 1, then 18 units/kg/h
-Enoxaparin: 1 mg/kg SQ BID (q12)
if CrCl < 30 mL/min : 1 mg/kg SQ daily (q24)
Monitor in Prophylactic Dosing
-usually not recommended
-consider when using enoxaparin at extremes of body weight or in patients with fluctuating renal function
Monitor in Full-dose Anticoagulation
-Heparin: Xa preferred over aPTT
Goal Xa 0.3-0.7 units/mL
-Enoxaparin: only at extremes of weight or fluctuating renal function
Goal Xa: 0.6-1 units/mL
WHY is a higher Xa level tolerated in Enoxaparin???
Warfarin MOA
-Inhibition of Vitamin K epoxide reductase complex 1 (VKORC1 -> inhibition of vitamin K reduction
-> result in depletion of factors needing Vitamin K for activation: 7, 9, 10, 2 SNOT
Onset and duration
Onset: 7-10 days -> need BRIDGING!
Bridging: additionally to Warfarin administer an injectable coagulant (heparin or lovenox) until Warfarin is working
when bridging do we fully anticoagulate or prophylactically???
Duration: days
How is Warfarin metabolized?
DDI
Hepatic (liver -> CYP2C9, 3A4, 1A2)
DDI: Fab 5
Fluconazole
Flagyl (Metronidazole)
FQ
Amiodarone
Bactrim
-> all are CYP2C9 inhibitors -> so with this 5 drugs the metabolism is inhibited -> the concentration of warfarin goes up -> BLEEDING
How is Warfarin monitored and reversed?
INR (ratio of clotting factor)
normal: 1
GOAL: 2-3 or 2.5-3.5
too high INR -> too much Warfarin, too thin
reversed by:
Vitamin K (is the API reduced (activated) Vitamin K???, is the vitamin K we eat reduced (activated)?
4 factor PCC (KCentra) - giving the missing clotting factors (SNOT)
Why does Warfarin take so long to work?
-long half-life (60h) of Factor II (most responsible for clotting) -> it takes time until all the Factor II is depleted (Vitamin K is needed for Factor II and blocked)
-Warfarin also inhibits Protein C and S (natural anticoagulant) -> short half-life
-so when starting Warfarin the ratio between Protein C and S is greater towards Factor II (long half-life) -> more Factor II -> prothrombotic
How does Warfarin DDI affect INR?
fe. Bactrim -> it will inhibit CYP2C9 and inhibits the metabolism of Warfarin -> higher concentration of Warfarin -> thinner blood -> higher INR
Counsel patients taking Warfarin and have Vitamin K reach foods
they should have consistent amounts of Vitamin K, to prevent fluctuations in INR level
What if they consistently have Vitamin K rich food, and increase warfarin dose?
Vitamin K-rich foods
-Leafy vegetables (kale, collards, spinach)
-Mayonnaise (full-fat, egg component)
-Cranberry
Dosing Warfarin
Prophylactic: not recommended for DVT or pt with risk of clots bc it takes too long (7-10d)
Full Anticoagualnt dose:
start with 5 mg PO daily
in patients who are elderly, and have liver disease (cirrhosis), known drug interactions (Fab 5) decrease to 2.5 mg PO daily
How long does it take to see a change in INR when changing the Warfarin dose?
3-5 d
-stick with one strength to prevent confusion
so don’t adjust the dose again if INR hasn’t changed before 3-5d
How will INR change if 1 dose of Warfarin is missed?
INR drops by 1
the full effect on INR is seen in about 3-5 d
To what extent should doses of Warfarin be changed?
increase or decrease by 10% of the weekly dose
fe. 30 mg weekly -> 10% = 3 mg -> change to 27 mg
When administering with Phenytoin, we reduce by 50% bc of the CYP interaction, shouldn’t it be 10%??? are there any other DI that require 50% reduction instead of 10%???
Monitoring of Warfarin
-Prophylactic: it is not given prophylactic
-Full dose:
Blood Clot: 2-3
Atrial Fibrillation: 2-3
with valves the risk is higher, pt have to stay in range
Mechanical Aortic Valve: 2-3 or
2.5-3.5
Mechanical Mitral Valve: 2.5-3.5
Starting dose of Warfarin in a patient (85 kg) clot taking levofloxacin?
a reduced dose of Warfarin bc of FQ
2.5 mg daily
Bridging: Lovenox 1mg/kg -> 85 mg subQ BID (if CrCl < 30: 85 mg subQ 1xd)
Bridge until the patient reaches 2 therapeutic INR 24h apart (around day 5-7)
INR = 1.6
Goal is 2 - 3
How to adjust the Warfarin dose
-Initial dose was 2.5 mg daily
-increase the dose, we need the blood to be thinner to reach a higher INR
-increase by 10% of weakly dose: 17.5 mg -> 10% = 7.5 mg -> 2.5 + 7.5 = 10 mg (new dose)
Which of the Anticoagulants has contraindications in pregnant women? (Category X)
Warfarin
