IC4&5 Flashcards
what are the three factors in the Virchows triad
1) hypercoagulability = blood
2) circulatory stasis = flow
3) vascular damage = vessel
what are the risk factors for hypercoagulability?
- major trauma or surgery
- pregnancy post partum
- IBD
- sepsis or infection
- autoimmunity
- malignancy
- dehydration
- inflmamation
- estrogen drug therapy
- antiphospholipid syndrome
what are the risk factors for circulatory stasis?
- varicose veins
- bradycardia or hypotension
- obstruction of venous flow = obesity, pregnancy, tumors
- immobility
what are the risk factors for vascular damage?
- atherosclerosis
- cellulitis
- venous catheter
- heart valves
- physical trauma, strain, injury
what are the other risk factors for VTE?
age (older = more risk, esp if >75y/o)
prior history to VTE.
what are the symptoms of DVT?
UNILATERAL LL swelling, redness, pain.
what are the signs of DVT
1) pain behind the knee upon dorsiflexion of feet of affected limb
2) dilated superficial veins of the affected limb
what are the symptoms of PE? state the reasons for these symptoms
1) SOB, palpitations, cough, chest pain, chest tightness.
2) hemoptysis
3) dizzy, lightheaded
embolism/clot flows to the vessels at the lungs, obstructing blood flow. this reduces gaseous exchange and transport of o2 to the other parts of the body = may result in circulatory collapse.
what are the signs of PE?
1) dilated neck veins
2) tachypnoea, tachycardia, diaphoretic
3) hypotension, cyanotic, LOW SPO2
4) possible cardiogenic shock leading to death
differential diagnosis of DVT?
1) cellulitis = also presents with erythema and pain
2) lymph odema, fluid retention = may present with swelling.
what are the signs of hemodynamic instability in PE?
1) cardiac arrest
2) obstructive shock
- systolic bp <90mmhg or require vasopressors to >90mmhg
- end organ failure: cold clammy skin, altered mental status, oliguria/anuria
3) persistent hypotension
- systolic bp <90mmhg or drop of >40mmhg (last more than15min).
differential diagnosis for PE?
myocardial infarction, angina?
other classification for high-risk PE?
RV dysfunction on tte/ctpa and elevated troponin levels
pesi class iii-iv (includes age, hx of hf, cancer, chronic lung disease, hr, altered mental status, bp, rr, temp… etc)
what is the wells DVT scoring
1) active cancer
2) bedridden >3 days, major surgery last 4 weeks
3) calf diff >3cm
4) entire leg swollen
5) collateral superficial veins (non-varicose)
6) pitting edema
7) localised tenderness distributed across the deep venous system
8) paralysis or immobility of the lower limb
9) diff diagnosis that exclude = -2
more than 2 than send for imaging (CUS, compression ultrasound)
what is the PE wells scoring
1) s/sx of DVT = 3pt
2) other diff diagnosis unlikely = 3pt
3) malignancy = 1pt
4) hemoptysis = 1pt
5) bedridden >3 days, major surgent last 4 wks = 1.5 pts
6) HR >100 = 1.5pts
7) previous vte/pe = 1.5pts
if >4 points = likely diagnosis for PE = send for CTPA/VQscan.
treatment algorithm for PE (high or mod risk)
if high risk:
- initiate either bolus UFH or thrombolytic therapy = weight risk vs benefit
- UFH recommended due to shorter half life = less bleeding risk esp for hemodynamically unstable patients.
- if thrombolytic therapy c/i, consider surgical pulmonary embelectomy.
if mid-low risk
- if parenteral, recommend LMWH eg enoxaparin over UFH.
- parenteral recommended due to faster onset and reliability while hospitalised (nurse administration)
if oral, recommend DOACs over VKA.
recommendation for treatment is 3 months
when to extend therapy for dvt/pe longer than 3 months
if unprovoked vte
check patient adherence
renal and hepatic impairment
weigh bleeding risk vs benefit of permanent/long term treatment
at least yearly monitoring is required eg rechecked bleeding risk
FYI conditions include medically ill eg sepsis and major surgery eg THR/TKR.
when is VKA recommended over DOACs for DVT PE
antiphospholipid syndrome
- should be on indefinite treatment with VKA eg warfarin
left ventricular thrombus
if patient has severe renal impairment crcl <30
- unable to use DOACs
- must be combined with UFH/LMWH that is dose adjusted for severe renal impairment
what happens if patient has active bleeding or current contraindication to anticoagulants
initiate on IVC (inferior vena cava; used to prevent the clot from travelling to lungs) filter first and start anticoagulants once bleeding is stopped or contraindication is resolved.
when to consider LMWH monotherapy
1) active cancer
- treat for 6 months then reassess
2) liver disease and coagulopathy
- warfarin not suitable as iNR may not reflect antithrombotic effect.
3) pregnancy
- vka contraindicated in first trimester
- doacs not well studied
what are the treatment algorithms for DVT
1) apixaban 10mg BD x 7 days > 5mg BD > 2.5mg BD
2) rivaroxaban 15mg BD x21 days > 20mg OM > 10mg OM
3) LMWH/UFH/fondaparinux x 5days then either dabigatran 150mg BD or edoxaban 60mg OD
4) LMWH/UFH/fondaparinux + PO warfarin for atleast 5 days and INR>2 (for 2 readings or 2 days in a row) THEN warfarin dose adjusted to maintain INR 2-3.
edoxaban VTEP dose and dose modification?
60mg PO OD
if crcl 30-50 or BW <60kg
= 30mg/day
compare the renal clearance of the DOACs
A < R < E < D
25 33 50 80
compare the metabolism of DOACs
edoxaban is minimally hepatic, (<4% by 3a4)
dabigatran is metabolised by plasma esterases (also minimally hepatic, 80% excreted unchanged as urine)
rivaroxaban (also 2j2) and apixaban undergo cyp3a4 metabolism
ALL are affected by PGP transporters.
(VTE) what is the renal adjustment for dabigatran?
crcl <50 and concomitant pgp inhibitors
= avoid
(VTE) what is the renal adjustment for apixaban?
15-29 caution
hd AVOID
(VTE) what is the renal adjustment for rivaroxaban?
<30 avoid
(VTE) what is the renal adjustment for edoxaban?
> 95 = not recommended
difference between the moa of the 4 doacs
only dabigatran is a direct factor iia antagonist, other three are direct factor xa inhibitors
what is the vtep dosing for dabigatran?
hemostasis achieved, start within 1-4h post surgery
TKR: 220mg/day x 10 days
THR: 220mg/day x 28-35days
if crcl30-50, caution, reduce to 150mg/day
what is the vtep dosing for rivaroxaban?
hemostasis achieved, start within 6-10h post surgery
TKR: 10mg/day x 2 weeks
THR: 10mg/day x 5 weeks
if medically ill, reduce dose to 10mg/day for up to 31-39 days
what is the vtep dosing for apixaban?
hemostasis achieved, start within 12-24h post surgery
TKR: 25mg BD x 10-14 days
THR: 25mg BD x 32-35days
what is the vtep dosing for edoxaban?
30mg/day
lab interferences of the 4 DOACs
derange PT/INR w/ apixaban, rivaroxaban, edoxaban
derange PTT and PT w/ dabigatran
VTET dosing for UFH?
80IU/kg loading, then 18IU/kg/hr maintenance
(IV)
VTET dosing for enoxaparin
SC DOSING
1.0mg/kg Q12
OR
1.5mg/kg OD (reduce to 1.0mg/kg OD if cccl <30)
VTEP dosing for enoxaparin
SC dosing
for surgical or medically ill:
40mg OD
THR/HFS
40mg OD or 30mg BD
for surgery = 10-14 days, up to 35 days.
crcl 30-50 for trauma patients = 30mg Q12.
crcl<30 for trauma patients = 20mg or 30mg OD.
VTEP dosing for UFH
medically ill: 5000 iu q8-12 for length of stay OR until fully ambulatory
non-ortho surg no cancer: 5000iu ≥2h prior to surgery, then restart after surgery until fully ambulatory/risk of dvt low
TKR THR: 5000iu q8-12h ≥12h pre op or ≥12h post op after hemostasis achieved. (10-35 days)
why is warfarin combined with LMWH/UFH
concern with hypercoagulable state due to reduction in protein c and s levels in the first few days which are responsible for anticoagulation
why is LMWH administered on admission over DOACs or VKA
if suspected, LMWH has fastest onset of action as it may take awhile for imaging to be ordered.
what are the diff types of AF and how do they differ in treatment
valvular AF
- mod-severe mitral valve stenosis
- presence of bioprosthetic or metallic heart valves. metallic heart valves have more thrombogenic risk
= preferred WARFARIN
(DOACs contraindicated)
non-valvular AF
- DOACs preferred
CHA2DS2Vasc components
C = congestive heart failure (including ventricular dysfunction, hypertrophic cardiomyopathy)
H = hypertension
A = age (65-74; ≥75) = 2 or 1 point
D = DM
S = prior stroke history or TIA = 2 points
Vasc = vascular disease (aortic plaque, PAD, prior MI)
consider if ≥ 1 or recommended if ≥2
weight adjustment for DOACs in SPAF
if <60kg, dose adjustment edoxaban and apixaban (avoid rivaroxaban and dabigatran)
if overweight >120kg OR BMI >40 , dose adjust apixaban and rivaroxaban (avoid edoxaban or dabigatran)
how to calculate BMI
weight in kg / (height in m)^2
HASBLED components
H: uncontrolled hypertension
A: abnormal renal (SCr > 200umol/L) or hepatic function (bilirubin >2x ULN or ALT/ALP >3x ULN)
S: stroke history
B: bleeding history
L: labile INR values, i.e., unstable, high INR, <60% TTR
E: elderly >65 or frail
D: drugs (eg nsaids) or alcohol (>14u men and >7u women per week)
what to check during follow up sessions
ABC-ST
adherence:
bleeding: check for each instance of bleeding (could be more serious etiology). check whether to revise dose if bleeding affects QOL
- check risk of falling.
concomitant
= medications: OTCs? eg NSAIDs
= conditions: address uncontrolled HTN esp >160
= alcohol intake
(MODIFY RISK FACTORS)
side effects: need to stop or temporary bridging?
thromboembolism: any stroke like symptoms
frequency of followup for DOACs (and what parameters to check)
check Hb, LFT, renal function test
yearly
otherwise
4 monthly: if ≥75-80y/o (esp if dabi or edox)
x monthly: if crcl <60 (crcl/10)
what are the lab tests to conduct for VTE patients prior to starting anticoagulants?
1) FBC, hematocrit, platelets, Hb
2) WBC = rule out cellulitis
procalcitonin = rule out cellulitis
3) PT/INR
4) ECG (exclude AMI leading to pulmonary edema)
5) troponin (exclude MI)
6) LFT = affects production of clotting factors
what is the dosing for dabigatran in SPAF? and dose adjustments?
150mg BD
110mg BD if ≥80y/o, use PGPi, HBR
CRCL
30-50 = no adj
<30 = contra (in sg)
what is the dosing for rivaroxaban in SPAF? and dose adjustments?
20mg OD
CRCL
30-50: 15mg OD
15-30: caution (HSA)
<15 = contra
what is the dosing for edoxaban in SPAF? and dose adjustments?
60mg OD
30mg OD if any (crcl 30-50, weight <60kg, concomitant verapamil, quinidine, dronedarone)
CRCL
30-50 = 30mg OD
<30 - no data
what is the dosing for apixaban in SPAF? and dose adjustments?
5mg BD
2.5mg BD if any 2 (>80y/o, <60kg, SCr >1.5mg/dL or 132.6mmol/L
CRCL
30-50 - no adj
15-29 = 2,5mg BD
<15 = unknown.
what drugs require dose adjustment with edoxaban (specific)
VERAPAMIL
QUINIDINE
DRONEDARONE
what is the formula for CG
crcl = (140-age) x BW (kg) x (0.85 if female) ÷ SCr (mg/dl) x 72
if overweight = x0.4 for adjBW
can use a range with
IBW and TBW
IBW =
Men: 50 + (0.91 × [height in cm − 152.4])
Women: 45.5 + (0.91 × [height in cm − 152.4])
which DOAC safest to give in renal impariment?
apixaban because it is only cleared 25% renally (least cleared renally compared to the other DOACs)
which DOAC is a OATP substrate
RIVAROXABAN
which DOAC is a BCRP substrate
apixaban and rivaroxaban
examples of pgp inhibitors?
1) azoles
2) macrolides
3) cvs drugs: verapamil, quinidine, dronedarone, amiodarone
4) ciclosporin
can hiv protease inhibitors be used with DOACs? what and why?
no
they are 3a4 inhibitors and pgp, bcrp inhibitors/inducers
e.g., ritonavir and other –navir drugs
can otc supplements (herbal drugs) be used with DOACs? and which ones
green tea, ginkgo, echinacea, curcumin, ginseng…
what are other examples of drugs to be used with caution with DOACs (excluding macrolides, azoles, antiarrythmatic drugs)
naproxen = pgp competition
st john worts = enzyme induction
SSRI and SNRIs = PD effect on platelets
H2RA, PPIs, antacids = affect GI absorption
what are some special characteristics of warfarin? what genetic polymorphisms affect warfarin?
S enantiomer is more active
S is metabolised by CYP2C9
R is metabolised by 3A4, 1A2, 2C19, 1A1.
polymorphisms in 2c9 and VKORC1 = BOTH increases sensitivity to warfarin = reduce dose.
how will alcohol binging affect warfarin doses
Alcohol binge = P450 inhibition = increase INR
decrease dose
how will chronic alcoholism affect warfarin doses
Chronic alcoholism = P450 induction = increases warfarin metabolism = decrease INR.
increase dose
how will sudden increase in phx exercise affect warfarin dose
Sudden increase in physical activity = increases warfarin metabolism = decrease INR.
increase dose
how will smoking affect warfarin dose
Smoking = P450 induction = increases warfarin metabolism = decrease INR.
increase dose
how does gut microbiome affect warfarin dose
Gut microbiome load = may require higher doses of warfarin.
o Higher gut microbiome = increased menadione (vit K derivative; involved in clotting cascade) = decreased INR.
o Use of antibiotics can disrupt gut bacteria and decrease menadione levels in the cut = more time to clot = increased INR.
how do infections/febrile states affect warfarin dose
increase turnover (metabolism) of clotting factors = INR increase.
how do fluid retention affect warfarin dose
o Heart failure or renal impairment may cause BOTH impaired absorption due to the oedematous gut AND liver impairment due to congestion.
o IF gut affected = malabsorption = esp in acute fluid retention = INR increases first before it drops over time (as gut malabsorption is more chronic).
o IF liver congestion > gut oedema = INR increase.
how does liver dmg affect warfarin dose
Liver damage:
o Liver is involved in clotting factor production and warfarin metabolism.
o Liver impairment/damage may result in decreased clotting factor synthesis and decreased warfarin metabolism = INR increase.
how does thyroid affect warfarin dose
o Hyperthyroidism increases clotting factor turnover = INR increases.
o Decreases in hypothyroidism.
when does warfarin require preemptive dose adj for certain drugs
Dose adjustments required for:
o Bactrim (sulfamethoxazole & trimethoprim): 25-50% depending on reference source.
o Ciprofloxacin: 20-30% depending on reference source.
o Rifampin
No need for dose adjustments:
o Macrolides.
o Amoxiclav.
o Doxycycline.
counselling points for warfarin?
no need to change your diet or avoid certain food due to its vitamin K content, as some of them such as dark green leafy vegetables contribute to a healthy diet. Keep intake consistent.
Write down the dates which you missed your dose
increase risk of bleeding and bruising. Some bleeding signs to look out for include nosebleeds, heavy menstruation, or gum bleeding. It may be necessary to switch to a soft-bristled toothbrush to reduce gum bleeding. Should you experience these side effects, please inform your doctor or pharmacist as soon as possible.
prolonged periods (more than 3 days) of fever, vomiting and/or diarrhoea, seek medical attention. Also, note down the dates and report them
how to switch from DOAC to warfarin and vice versa?
if warfarin to doac , wait 3 days and INR <2 before switching
= complete reversal only in 5-7days
if doac to warfarin, can switch immediately
what is the target inr range for mechanical heart valve? REASON?
2.5-3.5
high risk of thrombogenecity + likely to impose abnormal flow conditions
what to do if there is bleeding with DOAC
stop meds, consider concomitant meds
- check dose and other meds
- sample crcl, WBC, LFTs
if moderate severity (non life threatening)
- consider mechanical compression
- hemostasis eg via surgical
- fluid replacement
- consider adjunct tranexamic acid (reduces fibrolysis)
if life threatening severe
- consider idarucizumab for dabi and andexanet for other 3
- consider PCC(prothrombin complex concentrates)
how long to withhold DOAC before surgical procedure?
dabi:
low risk: 24-48 (increases with crcl, not indicated <30)
high risk: 48-96 (not indicated <30)
riva,edo,api:
low risk: 24 (36 if 15-30)
high risk: 48
should not use <15
consider age, stroke risk, bleeding risk any recent CVS events, renal function, comeds, comorb
consider risk level of stroke
warfarin reversal in high risk bleeding?
IV vit K (if INR >1.5) and PCC (preferred)
recheck PT INR PTT 1h later and repeat as needed.
locally only iv vit k available. risk of delayed recoagulation if initiated.
other reversal option for dabigatran?
consider dialysis
other reversal options of rivaroxaban and apixaban?
PCC prothrombin complex concentrate
