VTE pre Flashcards
Unfractionated heparin (UFH)
-rapid, parenteral
-anticoagulant
-variable dose response
-weight-based dosing
Variable dose response of UFH
=need for aPTT monitoring
-aPPT = activated Partial Thromboplastic Time
-goal: 1.5-2.5 time control
Unfractionated heparin weight-based dosing
-initial: 80 units/kg IV bolus then 18 units/kg/hr infusion
-APTT < 35s (<1.2): 80/+4
–APTT 35-45s (1.2-1.4): 40/+2
-APTT 46-70s (1.5-2.5): no change
-APTT 71-90s (2.6-3): dec infusion rate by 2
Weight-based dosing of UFH monitoring
-aPTT at baseline
-6h after dose or with each dosage for first 24h
-check daily after first day
Heparin Associated Thrombocytopenia (HAT)
-HIT-type I
-non-immune mediated
-mild dec in platelets
-49-72 hours after admin of heparin
-transient
-do not need to d/c heparin
Heparin Induced Thrombocytopenia (HIT)
-immune mediated
-thrombotic complications
-7-14 days after taking heparin
-can occur up to 9 days after d/c
-platelets drop > 50% from baseline
HIT management
-stop all heparin
-give alt anticoagulant
-do not give platelet infusion
-do not give warfarin platelet count > 150k
-evaluate for thrombosis
Low molecular weight heparin
-better than UFH
-good availability
-predictable dose response
-no resistance
-fixed or weight-based dosing
-no need to monitor
-longer half-life qd or BID
-improved absorption bc smaller
-reduced risk of HIT and maybe bleeding
Low molecular weight heparin drugs
-enoxaparin
-dalteparin
Enoxaparin dosing prophylaxis
-30mg SQ q 12h (surgery)
-40mg SQ qd (medical
Enoxaparin dosing for treatment
-1mg/kg SQ q12
-1.5mg/kg SQ qd
Enoxaparin dosing for renal dysfunction
-30mg SQ qd
-1mg/kg SQ qd
Dalteparin dosing for prophylaxis
-2500-5000 units SQ qd
-200 units/kg SQ qd 30 days then 150 units SQ qd (cancer)
Monitoring parametersLMWH
-anti-Xa levels
-consider in kids, kidney failure, obesity, long course, pregnancy
Anti-Xa tx
-BID 0.6-1 units/ml 4h post dose
-dq: 0.1-0.3 units/mL obtained as trough
-can consider peak 1-2 units/mL obtained 4h post dose
Fondaparinux
-injectable Xa inhibitor (FXa)
-prophylaxis follwoing THA, TKA, hip replacement, ab surgery
-tx of DVT or PE
Fonaparinux dosing prophylaxis
-2.5mg SQ qd (hip, knee, ab surgery)
Fonaparinux dosing for DVT or PE tx
-<50kg: 5mg
-50-100: 7.5mg
->100: 10mg
-SQ qd
Fondaparinux considerations
-dont use in renal dysfunction (CrCl <30)
-do not use for prophylaxis w low body weight
-can use in HIT
-no monitoring
-pregnancy category B
IV direct thrombin inhibitors
-Lepirudin
-Bivalirudin
-Argatroban
Lepirudin
-IV direct thrombin inhibitor
-tx HIT
-0.15mg/kg/h +/1 0.4mg/kg bolus
-reduce dose if CrCl <60ml
Bivalirudin (angiomax)
-IV direct thrombin inhibitor
-0.7mg/kg then 1.75 mg/kg/h
-tx HIT, UFH alt during PCl
Argatroban
-2mcg/kg/min
-tx HIT
-elevates INR, overlap w warfarin unitl INR >4
-cautionhepatic dysfunctoin (0.5mcg)
Warfarin
-1-6mg
-2.5, 7.5, 10mg
-PO
-all tablets same color
Challenges of Warfarin
-narrow therapeutic window
-subject variability
-interactions
-labs hard to standardize
-good PK/PD understanding by bot patient/provider
Warfarin MOA
-inhibits enzymes that convert vit K
-inhibits Factors II, VII, IX, X
-inhibits protein C and S
-doesnt effect already formed thrombi
Warfarin PK
-effect within 24h
-peak 72-96h
-2-5 day duration
-CYp450 metabolism in liver
half/life of vit K factors
-prothrombin (II): 60-100h
-VII: 4-6h
-IX and X: 20-40
Warfarin genetic variances
-CYP2C9
-VKORC1
CYP2C9 and warfarin
-dec Cl 40-90%
-lower dose requirement
-some more common in asians and AA
-inc bleeding risk and longer time to goal
VKORC1 and warfarin
-dec production
-inc sensitivity (A lower the dose avg to 3mg)
-inc resistance (inc dose avg 6mg)
-mostly white and asian
Who to test
-if available before 6th dose and patient is at high risk of bleeding if INR increases
Warfarin-drug interactions that increase INR
-Mteronidazole
-Amiodarone
-Fluconazole
-Ciprofloxacin
-Bactrim
-alcohol
-liver disease
Warfarin drug interactions that decrease INR
-Rifampin
-also alcohol
Aspirin and NSAID
-inc bleeding risk but not INR
Food interactions w Warfarin
-activity reversed by vitamin K
-need to pt educate
Acute alc use and warfarin
-inc warfarin effect by inhibiting metabolism
Chronic alcohol use and warfarin
-enhances metabolism by inducing hepatic enzymes
=DEC effect of warfarin
Chronic alcohol use w liver damage and warfarin
-inc effect bc no hepatic enzymes
=lower dose
Antiplatelet drugs
-Aspirin (COX)
-ADP inhibitors
-GPIIB/IIIa blockers
-P3 inhibitors (dipyridamole)
-protease-activated receptor inhibitors
Antiplatelet use in VTE
-limited use
-ASA for CHADSVASC score 1
-dipryidamole w warfarin for prostetic heart valves
-adj role to thrombolytics
-significant role in ACS and other arterial ischemic vascular disorders
Bleeding management
-d/c med
-apply compression
-maintain BP
-surgery
-blood products +/- PCC +/- targeted antidotes
-consider activated charcoal < 2h bleeding
-hemodialysis dabigatran only
-tranexamic acid
Targeted reversal of bleeding
-UFH, LMWH: protamine sulfate
-Dabigatran: idaruxizumab
-factor Xa inhibitors: andexanet
Protamine sulfate
-UFH and LMWH antidote
Protamine for UFH infusion
-1mg protamine per every 100 units UFH given over past 3 hours
Protamine for LMWH
-within 8 hours: 1mg/100 anti-Xa units and 1mg/1mg enoxaparin
-after 8 hours: 0.5/100 and 0.5/1
Protamine sulfate adverse reactions
-HYPOtension
-bradycardia
-slow infusion over 1-3 minutes
-max 50mg over 10 minutes
Idarucizumab
-direct binder to dabigatran (higher affinity than thrombin)
-2 2.5g doses less than 15 min apart (5g IV)
-monitor aPTT repeat in 2 hours then q12h til normal
Idarucizumab side effects
-delirium
-HA
-hypokalemia
-constipation
-pneumonia
-fever
Andexanet alfa
-binds and sequesters FXa inhibitors (rivaroxaban and apixaban)
-no monitoring
Andexanet alfa dosing
-low dose if less than or equal to 5mg apixaban or 10mg rivaroxaban
-high dose if over
-if more than 8h then use low dose
Low dose andexanet alfa
-400mg IV bolus at 30mg/min then 4mg/min IV infusion for up to 120min after 2 min
High dose andexanet alfa
-800mg IV bolus at 30mg/min then 8mg/min IV infusion for up to 120min after 2 min
Andexanet alfa side effects
-site reaction
-DVT
-stroke
-AMI
-PE
-UTI
-pneumonia
Warfarin bleeding management
-depends on INR and presence/absence bleeding
-Vit K (5mg PO)(anaphylaxis over 1mg/min IV)
-fresh frozen plasma (10-15ml/kg)
-Prothrombin Complex concentrate (30IU/kg) check INR before and 30-60 min
Warfarin bleeding management w INR 4.5-10 and no bleeding
-avoid vit k
Warfarin bleeding management w INR >10 and no bleeding
-PO vit K 5mg
Major bleeding while on warfarin
-PCC preferred of FFP
-may add vit k 5-10mg too
Warfarin rapid reversal
-15 min
-Prothrombin complex concentrate (PCC) + IV vit K
Fast warfarin reversal
-Fresh frozen plasma
-10-15ml/kg
Prompt warfarin reversal (4-6h)
-IV vit K
-do not exceed 1mg/min
slow warfarin reversal (24h)
-PO vit K
Very slow warfarin reversal (3-5 days)
-d/c warfarin
VTE prophylaxis
-UFH
-LMWH
-Factor Xa inhibitors
-Vit K antagonists
Low VTE risk
-minor surgery
-full ambulatory med pt
-NO tx needed
-early and aggressive ambulation
Moderate VTE risk
-gen surgery pt
-tx w UFH, LMWH, Factor Xa inhibitor (fondaparinux)
-continue prophylaxis 28 days after hospiral discharge
Moderate VTE risk in acutely ill medical pt
-UFH, LMWH, fondaparinux, rivaroxaban (31-39days total), betrixaban (35-42)
High VTE risk
-orthopedic surgery
-LMWH
-fonaparinux
-rivaroxaban
-dabigatran (hip)
-UFH
-vit K antagonist
-continue 10-14 days post op consider 35 days
High bleeding risk
-mechanical prophylaxis preferred
-intermittent compression devices
-foot pumps
-compression stockings
slide 61
slide 62
CHA2DS2-VASc score
-risk factors for stroke of systemic VTE
-PO anticoagulation if over 2
HAS-BLED score
Atrial fibrilation
-afib inc risk of stroke or systemic VTE 5fold
-anticoagulant therapy reduces risk
