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Anticoagulation I Dr. Covert Flashcards

Dr. Covert EXAM IV (41 cards)

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1
Q

What factors contribute to Thrombosis?

A

Virchow’s Triad

-Endothelial Injury
-Abnormal Blood flow (long travel)
-Hypercoagulability (contraceptives, pregnancy, cancer therapy)

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2
Q

What tests assess clotting disorders?

A

intrinsic: PTT (play table tennis - inside)
normal: 25-35 sec

extrinsic pathway: PT (play tennis - outside)
normal: 12 sec

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3
Q

Reasons for prophylactic anticoagulation therapy

A

Some risk of clot
-Immobility in hospitalized patients (some) changes in blood

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4
Q

Reasons for full-dose anticoagulation

A

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

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5
Q

What are the available Anticoagulants and MOA?

A

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)

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6
Q

Indication for Anticoagulants

A

-DVT
-PE
-Atrial fibrillation

-red clot: fibrin rich

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7
Q

What is the MOA of Antiplatelets?

A

MOA: inhibit platelet aggregation
drugs: Aspirin, P2Y12 inhibitors (clopidogrelel, prasugrel, ticagrelor)

white clot: platelet-rich

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8
Q

Indication of Antiplateteltes

A

-prevents platelet clots, makes the blood slippier

Indication:
-Ischemic stroke (preventing platelet clot -> stroke)
-coronary artery disease (CAD)
-peripheral artery disease

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9
Q

What are the injectable Anticoagulants?

A

-Unfractionated Heparin (UFH)

-Enoxaparin (LMWH)

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10
Q

MOA Heparin

A

-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

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11
Q

How is heparin cleared?

A

Reticuloendothelial system (binds to endothelial cells)

NOT hepatically or renally cleared

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12
Q

Which tests are used to assess the activity of heparin?

Therapeutic drug monitoring

A

-heparin works on the intrinsic pathway

-aPTT, anti-Xa

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13
Q

What are the side effects of heparin and how can it be reversed?

A

ADE: Heparin-induced-thrombocytopenia (immune cells activate platelet-clotting), bleeding

-reverse agent: Protamine

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14
Q

Heparin-induced-thrombocytopenia

A

-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

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15
Q

Platelet level in patients with HIT

A

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)

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16
Q

MOA Enoxaparin (LMWH)
Lovenox

A

Potentiates ATIII activity; Inactivates Factor Xa more than Factor II due to the short tail

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17
Q

Onset and duration Enoxaparin

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A

Onset: SQ 1-3h

Duration: SQ 5-8h

18
Q

How is Enoxaparin cleared?

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A

Renally eliminated

19
Q

Which heparin to use in dialysis patients or patients with poor kidney function?

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A

Heparin

Enoxaparin is cleared renally

if the patient’s kidney is fine, can we still give heparin???

20
Q

Which test to assess enoxaparin activity?
Therapeutic drug monitoring

21
Q

ADR and reversing agent of enoxaparin

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A

-less risk for heparin-induced-thrombocytopenia, bleeding

-reversing agent: Protamin
-> if patient is excessively bleeding, vomit blood, blood in stool

22
Q

Prophylactic dosing Enoxaparin and heparin

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A

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

23
Q

Full-dose Anticoagulation

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A

-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)

24
Q

Monitor in Prophylactic Dosing

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A

-usually not recommended
-consider when using enoxaparin at extremes of body weight or in patients with fluctuating renal function

25
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???
26
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
27
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
28
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
29
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)
30
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
31
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
32
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
33
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
34
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
35
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
36
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%???
37
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
38
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)
39
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)
40
Which of the Anticoagulants has contraindications in pregnant women? (Category X)
Warfarin
41

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