Antithrombotics PAD, VTE Flashcards
HTN, statins, endocarditis summary table
learning objectives with antithrombotics
Antithrombotics
Layman term?
Which are antiplatelets 4
Anticoagulants 4
Fibrinolytics? 1
ASA
Low dose?
Daily dose for LT CVD prevention?
81mg baby aspirin
162mg daily
ASA is also contained in which common OTC meds? 3
4 factors that can lead to ASA resistance?
Salicylate acid can be deadly, what are the early signs?
What are the late signs?
—alka-seltzer
—excedrin
—fiorinal
resistance
—adherence
—poor absorption
—drug interactions
—COX / GP polymorphisms
salicylate toxicity
—early moderate:
N/V 🤮, tinnitus 👂, vertigo 💫😵💫, tachypnea 😮💨, tachycardia 🫀⏫
—severe:
acidosis, agitation, delirium, hallucinations 💭, convulsions, lethargy 🥱, stupor
What is the main ADP inhibitor? aka?
Which CYP enzyme does it need to be converted to its active metabolite?
—clopidogrel (Plavix ® )
—aka: P2Y12 antagonist
MOA
—inhibit ADP pathway of platelets by irreversibly blocking P2Y12 receptor on platelets
—Needs CYP2C19, only 15% active drug gets through
Clopidogrel
Brand name?
Drug type?
Indication? 3
Key toxicities
Contraindicated with which drugs?
Clinical pearls?
Plavix
P2Y12 antagonist
—antiplatelet
—blocks the P2Y12 receptor on platelet
Indications
—stroke
—ACS
—PAD
C/I
—do not prescribe to patients with a loss of function allele of CYP2C19
—rifampin
—omeprazole
Toxicities
—bleeding
—dyspnea w/ Ticagrelor
Which other OTC drugs interact with CYP2c19 and thus affect metabolism of Clopidigrel (Plavix)
Omeprazole is the main one
PPI for GERD etc
PAD
What are the non-pharm mngt options?
What are the pharm options? 6
—statin (high intensity/max tolerated)
—aspirin or clopidogrel (antiplatelet)
—rivaroxaban w/ low dose aspirin
—cilostazol (antiplatelet) to improve symptoms and walking distance but no major CV benefit
often d/t due to SX of headache, diarrhea, dizziness, palps.
—anti HTNs if applicable
—influenca vaccine (all CVD patients)
Peripheral vasospasm - Raynaud’s disease
What are the non pharm and pharm management options? 3
—quit smoking
—stay warm
—DHP CCBs such as Nifedipine
—a1-antagonist (Prazosin)
—PDE-5 inhibits (sildenafil)
Familiarise yourself with this coagulation cascade
What are the goals of care (indications) for anticoagulants?
—proph for primary or recurrence of thromboembolism
—prevent further clot extension
—prevent complications of embolism
—they do not have an effect on established thrombi, i.e they are not clot busters.
—takes days-weeks to improve.
Heparin
Aka?
MOA?
Where does it act on the coag cascade?
⭐️Indications 5
When does it act?
What is the antidote?
⭐️ ADRs 3
What must you monitor? 3
—unfractionated heparin
—induces conformational change of anti-thrombin
—thus inhibiting Xa and IIA (thrombin)
—rapid onset 6h “quick on/quick off”
Indications
—arterial thromboembolism
—PE
—acute MI
—prevention of VTE in hospitalised pts
—bridging before surgery
Antidote
—protamine
Monitoring
—platelets
—aPTT (intrinsic pathway)
—anti Xa
ADRs
—bleeding
—stroke
—HIT
LMWH — generic and brand name?
MOA?
Lab monitoring?
Indications
Pregnancy?
Antidote?
Toxicity?
—enoxparin (Lovenox ® )
MOA
—inhibits Xa
—longer duration of action
—greater bioavailability
—SC administration
Indications
—all coagulation tx and prophylaxis
Toxicities
—HIT
—injection site
Antidote
—protamine
no lab monitoring
preferred agent in pregnancy
HIT
What should you monitor when starting heparin?
always monitor platelet count
Stop heparin if HIT suspected
DOAC
What are the two main direct Factor Xa inhibitors?
Generic and brand names?
MOA
Lab monitoring?
Reversal agent official and preferred?
—RivaroXaban (Xarelto)
—ApiXaban (Eliquis)
—directly inhibit Xa
—no lab monitoring
—antidote is officially: andeXenet Alfa
—but in practice, hospitals use prothrombin complex concentrates off label
—prevention and treatment of VTE post surgery
What is the main direct thrombin inhibitor?
Generic and brand name?
MOA
Indication?
Lab monitoring needed?
Reversal agent?
—DAbigatran (Pradaxa ® ) (PO)
—prevents conversions of fibrinogen to fibrin by directly inhibiting thrombin (IIA)
—VTE treatment and proph
—afib
—antidote: iDArucizumab
—no lab monitoring
Out of these DOACs
Which can be used for:
—VTE treatment
—VTE prophylaxis post hip/knee surgery
—VTE prophylaxis in medical pts
—what are the reversal agents?
—which are CYP34A substrates?
—which are major P-gp substrates?
—all are approved for what?
—all are cleared how?
DOACs
What are the two BBWs?
—premature discontinuation increases risk of thrombotic events
—if given around same time as spinal/epidural, could result in hematoma or paralysis
Which anti-coagulant is a vitamin K antagonist?
Generic and brand name?
MOA?
Indication? 3 main
Onset?
Duration?
Goal INR?
Contraindicated for?
Antidote? 2
ADRs 2
—warfarin (Coumadin ® )
—impairs post-translational modification of factors 10, 9, 7, 2, C & S b/c they depend on Vit K
—slow onset b/c doesn’t work on existing factors, only new factors
—duration: 2-5d
—goal INR: 2-3
—contraindicated in pregnancy
—antidote: vitamin K/phytonadione or PCC/Kcentra
—ADRS: purple toe and skin necrosis
What does bridging mean?
Which agent would you use?
—enoxaparin (Lovenox) (LMWH)
What are the two warfarin-related toxicities other than bleeding?
Warfarin has many key variables and interactions and as such has very high dosing variability due to patient factors/food
—what are the PK interactions
—what are the PD interactions
—what are the 2 main food interactions?
—what are the 2 medical conditions
—which two genetic disorders play a role?
Must know:
—vitamin K interacts w/ metronidazole and TMP/SMX
—alcohol changes warfarin metabolism
—change in vitamin K intake affects warfarin efficacy
What is the takeaway regarding Vitamin K dietary intake for patients on Warfarin?
Patients should have a consistent intake of vitamin K rather than avoiding altogether
Warfarin dosing titration
What are the two key principles relating to:
—onset of action?
—long term dosing?
—what are you checking?
Relationship between Warfarin and INR
—how long does it take for a dose change to take effect?
—antidote, how long dose Vit K take?
—antidote, how long does factor replacement take>
—for an INR of 3.5-5, what are you going to do?
—INR of 5-9?
—INR of >9
—life threatening bleeding
—3-4 days for effect
—vit K = 12 hours
—PCC = almost immediately (emergency reversal)
—INR 3.5-5: lower or omit warfarin dose
—INR 5-9: hold next 1-2 warfarin doses and consider oral vitamin K
—INR >9: hold next 1-2 warfarin doses and administer oral vitamin K
—life threatening bleeding: discontinue warfarin / PO vitamin K / PCC
What labs do you check prior to starting any coagulant?4
bleeding risk
—CBC: H/H, PLT
—LFT
—Coags, PT/INR, PTT
dosing
—renal fxn
Keep food/drug interactions in mind
Which monitoring labs do you need for:
—clopidogrel
—heparin
—warfarin
—before you go to WAR, you need to do PT
What are the main fibrinololytics
Which other two analogs are there?
Where in the pathway does it activate (MOA)?
What is the indication?
What is the risk?
What is the follow on treatment?
—t-PA: tissue plasminogen activator
—activates plasminogen and plasmin which degrade fibrin
—(as a side note, aminocaproic acid/tranexamic acid inhibits this pathway, thus preventing the breakdown of clots, hence it’s use in stopping bleeding)
—alteplase & tenecteplase
—BLEED RISK IS HIGHER!
—indication: lysis of acute pathological fibrin clots
—acute stroke
—acute coronary syndrome
—acute PE, unstable
—acute PAD
—can be given systemically (higher risk for bleeding elsewhere in the body) or catheter directed, which is more targeted AT the clot
—follow up with anticoagulant
Which anticoag combos are okay?’
Which are not okay?
✅ antiplatelet like aspirin + anticoag
✅ dual antiplatelets aspirin + ADP/P2y12 inhibitor, or aspirin + PDE inhibitor
✅ dual antiplatelets + anti-coag: rarely used
❌ dual ANTICOAGULANTS/DOACs like Pradaxa (direct thrombin) + Lovenox
What are the DVT risk factors:
Major 3
Minor 4
Persistent 1
What is Virchow’s triad?
Virchow’s triad: thrombosis
1. Endothelial injury (break the skin)
2. Venous stasis (sit around)
3. Hypercoagulability (clot like crazy)
major
—surgery w/ anesthesia >30 mins
—hospitalised, bed ridden >3 days w/ acute illness
—c-section
minor
—surgery w/ anesthesia <30 mins
—hospitalised, bed ridden <3 days w/ acute illness
—estrogen therapy
—pregnancy
persistent
—cancer
What is the antithrombotics therapy DURATION for VTE disease?
Acute VTE event
➡️ initiate tx 5-21 days
➡️ tx duration = 3-6 months with a full dose anticoag
➡️ if high risk, may have indefinite treatment. ESP for pts w/ high risk of recurrence. Dose is lower. Goal is prophylaxis
DVT treatment
What is the tx duration?
Which med class is preferred?
If cancer, which med?
If APS, which med preferred?
If pregnant which med preferred?
Tx for proximal DVT?
Tx for distal DVT?
Tx for superficial DVT?
—tx: at least 3mo
—DOACs preferred
—cancer: anti Xa preferred (apixaban/eliquis or rivaroxaban/xarelto)
—APS: warfarin
—pregnant: LMWH
—proximal: anticogulate!!
—distal: (calf) serial imaging over 2w. If severe w/ SX anticoagulate
—superficial: if risk of progression, lose dose fondaparinux or rivaroxaban preferred x45d
VTE > PE treatment, how do you treat:
Subsegmental PE and no proximal DVT of the legs
Incidental finding of PE and asymptomatic
** Acute PE**
Low risk PE
acute PE»_space;> fibrinolytic like t-PA
VTE treatment
When do you choose LMWH or UFH over oral agents (DOACs)
—severe symptoms
—impending surgical interventions
—pregnancy
—unable to take orals
When is VTE prophylaxis required? 2
—all hospitalised patients
low dose LMWH
low dose SC heparin
low dose rivaroxaban
—following hip/knee arthroplasty
