cardio: thrombosis Flashcards
1
Q
thrombosis
A
process involved in the formation of a fibrin blood clot, contributed by platelets and clotting factors
2
Q
embolism
A
process by which any intravascular material migrates from its original location to occlude a distal vessel
- blood clot (thrombosis)
- fat
- air
- amniotic fluid
- tumour
3
Q
primary hemostasis
A
platelet adhesion, activation, and aggregation
4
Q
secondary hemostasis
A
clotting cascade
- once activated -> generates thrombin -> fibrin
5
Q
function of the hemostatic system
A
- to react to vascular injury
- to close the vessel wall defect
- prevent further bleeding
- maintain our blood in a fluid state
6
Q
arterial thrombosis, typically caused by
A
- rupture of the atherosclerotic plaques
- AF, blood clots from heart (cardioembolic source - use anticoag)
7
Q
venous thrombosis, typically caused by
A
a combi of factors from the Virchow’s triad
8
Q
diseases a/w arterial thrombosis
A
ACS, ischemic stroke, limb claudication/ischemia, mesenteric artery ischemia
9
Q
location of arterial thrombosis
A
left heart chambers, arteries
10
Q
location of venous thrombosis
A
venous sinusoids of muscles and valves in veins
11
Q
diseases a/w venous thrombosis
A
dvt, pe
12
Q
composition and treatment of arterial thrombosis
A
mainly platelets, some fibrin and occasional leukocytes -> antiplatelets
13
Q
composition and treatment of venous thrombosis
A
mainly fibrin and erythrocytes -> anticoagulation
14
Q
platelet-rich thrombus
A
‘white clot’
- atherosclerotic plaque rupture
- exposure of lipid core to blood
- platelet activation and aggregation
15
Q
fibrin-rich thrombus
A
‘red clot’
- AF: formation of LAA (left atrial appendage) thrombus
- activation of coagulation cascade
16
Q
deep vein
A
iliac, femoral, poplitical, tibial veins
- major role in propelling blood toward the heart (muscles surrounding the deep vein help to force the blood towards the heart, with help of one-way valves)
17
Q
when circulation of the blood slows down due to illness, injury or inactivity……
A
blood can accumulate or ‘pool’ which provides an ideal setting for clot formation
18
Q
DVT risk factors
A
- age: doubles with each decade >50yo
- venous stasis: immobility, major surgery, general anesthesia for >30min
- vascular injury: indwelling venous catheters, major orthopedic surgery, trauma
- hypercoagulability: malignancy, pregnancy/postpartum, clotting factor deficiencies
- drug therapy: estrogen replacement
19
Q
s/sx of DVT
A
- discoloration of the elf: pallor from arterial spasm, cyanosis from venous obstruction, reddish color from perivascular inflammation
- calf or leg pain or tenderness
- swelling of the leg or LL
- warm skin
- surface veins become more visible
- leg fatigue
20
Q
diagnosis of DVT
A
- clinical features
- history, risk factors and physical examination
- tests for definitive dx: venography (x-ray imaging of the leg via injection of contrast), impedance plethysmography (sensing changes in blood vol via use of electrodes)
- venous ultrasonography (most common, uses ultrasound to see if there is any abnormality in blood flow)
21
Q
pathophysiology of PE
A
DVT breaks off (embolus) and travel in the circulation, getting trapped in the lung, where it blocks the oxygen supply
22
Q
risk factors of PE
A
- hx of vte
- recent surgery
- immobilisation
- stroke
- obesity
- htn
- malignancy
-> BUT absence of risk factors does not exclude dx of PE (many patients have no identifiable risk factors!)
23
Q
s/sx of PE
A
SOB, tachycardia (>100bpm), tachypnea (>20bpm), sweating, apprehension (anxiety or a feeling of impending doom), sharp chest pain, cough, blood sputum, fainting
24
Q
one of the most popular scoring system for PE dx
A
Well’s criteria for predicting the probability of PE
- helps to decide what further diagnostic testing (venous ultrasonography, CT pulmonary angiogram) may be necessary
25
treatment of VTE
anticoagulation:
- SC LMWH
- IV UFH
(after acute phase)
- DOACs
- warfarin
26
stroke risk factors, modifiable
htn, dm, smoking, hld, physical inactivity
27
stroke risk factors, non-modifiable
age>80y, race and ethnicity, sex (generally men>women, except ages 35-44y and >85y), FH and genetic disorders eg, sickle cell disease
28
stroke diagnosis
- history and physical examination
- neurologic evaluation: stroke scales
- brain imaging: NCCT, DW-MRI
29
treatment of acute ischemic stroke
tPA (tissue-type plasminogen activator, recombinant form of endogenous protease)
-> binds to fibrin in thrombus -> converts entrapped plasminogen to plasmin -> initiates local fibinolysis
30
secondary prevention for non-cardioembolic (atherothrombotic) ischemic stroke
antiplatelet (white clot)
31
secondary prevention for cardioembolic ischemic stroke
anticoagulant (red clot)
32
AF -> ischemic stroke?
AF is an independent risk factor for ischemic stroke
- impaired atrial cotnraction -> blood stasis (abnormal blood flow) -> increase thromboembolic risk
33
DOACs have a lesser risk of ____________ than warfarin
intracranial bleeding
34
use of DOACs vs warfarin, which is preferred in pt with severe renal impairment?
warfarin
35
use of DOACs vs warfarin, which is preferred in pt with valvular AF?
warfarin
- AF with rheumatic mitral stenosis, a mechanical or bisprosthetic heart valve, or mitral valve repair
- insufficient evidence for DOACs in this area
36
indications for anticoagulant therapy
pathologic thrombus formation:
- dvt, pe
- acs (unstable angina, acute MI)
- intracardiac thrombus formation
prophylaxis:
- orthopedic, general surgery patients
- bridging therapy
- prophylactic flushes to maintain potency of lumen catheters
37
full effects of warfarin depends on
- inhibition of vit k-dependent clotting factors production
- depletion of previously synthesised vit k-dependent clotting factors
38
early in warfarin treatment (within 24hr), INR can
increase, secondary to depletion of factor 2 (shortest t1/2 = 6h)
39
full anticoagulant effect of warfarin only seen after
5-7 days of treatment, when factors 2 and 10 (longest t1/2) are depleted
40
prothrombin time
- measures how long it take for blood to clot
- normal: 12sec
- prolonged by deficiencies of clotting factors SNOT
41
what is the problem with using PT for lab monitoring?
no standardised thromboplastin reagent -> significant variability in PT
42
INR
- mathematical 'correction' of PT
- baseline: 1
INR = (PT of patient/PT mean normal)^ISI
ISI = international sensitivity index used at the local lab to perform the PT measurement
43
higher the INR
greater the anticoagulant effect -> 'thinner'
44
HAS BLED score
Hypertension (uncontrolled >160mmHg)
Abnormal renal/liver disease - 1 point each
Stroke
Bleeding tendency/predisposition
Labile INR
Elderly>65yo
Drug or alcohol - 1 point each
45
precautions during initiation of warfarin - assessing patient's sensitivity to warfarin using these factors (risk of over anticoagulation and bleeding is increased with the following):
- age>70
- weight<50
- baseline INR>1.4 or low platelet count<50k
- history of falls or GI bleed
- severe CHF or liver disease
- presence of malignancy
- malnutrition
- major surgery within 10-14 days
- ddi eg, amiodarone, rifampicin
- HAS BLED >= 3
46
treatment of overanticoagulation by warfarin
- hold and/or reduce dose
- vitamin K1 (phytonadione): PO, IV
47
choose dose carefully based on INR level and s/sx of patients to avoid......
initial resistance to subsequent warfarin therapy
48
factors affecting warfarin therapy
- age
- ethnicity: asians tend to have higher warfarin sensitivity
- gender: F>>>M
- recent surgery: incr risk of bleeding -> incr INR
- undernourished or NPO x more than 2 days: initiate warfarin at dose of =<5mg
- fever or diarrhea, incr warfarin sensitivity
- alcohol: acute incr, chronic decr INR
- smoking, may incr or decr INR
- exercise/activity
- underlying disease states
- non-adherance
- diet
- drug- and herb- interactions
49
factors affecting warfarin therapy: underlying disease states
- CHF/liver disease: initial dose =< 5mg
- hyperthyroidism, incr INR
- hypothyroidism, decr INR
50
factors affecting warfarin therapy: diet
- vit k-rich foods, decr INR: dark green, leady vege eg. kale, spinach, turnip greens, chick peas, cauliflwoer, cabbage, asparagus, broccoli, brussels sprouts
- meat: beef liver, pork liver
- fruits: avocado, apple, banana, orange, peas
51
drugs that incr INR
- inhibit catabolism of clotting factors: thyroid hormones
- inhibition of warfarin metabolism (non-PK): paracetamol>2g/d, allopurinol, azithromycin, simvastatin, TCAs, sulfamethoxazole
- inhibition of warfarin metabolism via 2c9: amiodarone, celecoxib, metronidazole, sulfamethoxazole
- inhibition of warfarin via cyp3a4: ciprofloxacin, clarithromycin, erythromycin, isoniazid, itraconazole, ketoconazole
- inhibition of warfarin via 1a2: FQ
52
drugs that decr INR
- incr synthesis of clotting factors: vit K, estrogens
- decr catabolism of clotting factors: PTU
- induce warfarin metabolism via 3a4: cbz, rifampin
53
herbs that incr bleeding risk
garlic, ginger, gingko
54
herbs that decr INR
- contains vit K derivatives: green tea, coQ10
- induces cyp3a4: st john's wort
- unknown: ginseng
55
warfarin adverse effects
most common: bleeding
rare: skin necrosis, purple toe syndrome
56
skin necrosis
- extensive thrombosis of venules and capillaries within SQ fat, involving abdomen, buttocks, thighs or breasts
- due to protein C or S deficiency
- onset: within 1-10 days of warfarin initiation
57
purple toe syndrome
- release of atheromatous plaque emboli to cause systemic cholesterol microembolism
- incr risk in pt with protein C deficiency
- onset: 3-10 weeks after warfarin initiation
- toes painful, purple
58
in pt with swallowing difficulties, can dabigatran capsules be opened?
no! dabigatran should not be opened in view of the dramatic increase in bioavailability
59
in pt with swallowing difficulties, can rivaroxaban be crushed?
yes! suspend in 50ml of water, stable in water for up to 4 hours
- not suitable for feeding tubes that do not terminate in the stomach eg. nasojejunal, PEJ
60
in pt with swallowing difficulties, can apixaban be crushed?
yes! may be crushed and suspended in water, or D5W via oral or nasogastric tube, stability up to 4 hours
61
monitoring for anticoagulants
- routine monitoring using clotting test (PT, INR, aPTT, FXa) not recommended
- renal function: baseline and at least every 3-6 months after, or during acute illness that may worsen renal function
- liver function: baseline and yearly after, every 3-6months for patients at risk of hepatic dysfunction
- cbc: baseline and at regular intervals (at least yearly), assess trends in Hb/Hct
- s/sx of blood loss
62
symptomatic management of bleeding for pt on anticoagulants
- mechanical compression
- surgical intervention
- fluids for hemodynamic support
- blood products
63
antidote for rivaroxaban and apixaban
coagulation factor Xa (recombinant), inactivated-zhzo
64
antidote for dabigatran
idarucizumab
65
rivaroxaban dose in stroke prevention for non-valvular AF
CrCl>50: 20mg OD
CrCl 15-49: 15mg OD
66
rivaroxaban dose in treatment or prevention of DVT
day 1-21: 15mg BD
from day 22: 20mg OD
after 6months: 10mg OD or (if high risk of VTE recurrence: complicated comorbidities, recurrent DVT/PE on extended prevention) 20mg OD
67
rivaroxaban dose in prevention of VTE after elective hip or knee replacement surgery
10mg OD x5w (hip) or 2w (knee)
68
rivaroxaban, not recommended for use:
- Under 18 years of age
- CrCl <15 ml/min
- Concomitant treatment with strong inducers or inhibitors of both CYP3A4 and Pgp
(e.g. azole, HIV protease inhibitors )
- Hepatic disease associated with coagulopathy and clinically relevant bleeding
risk
--Avoid use in moderate to severe hepatic impairment (Child-Pugh Class B and C cirrhosis)
69
For patients treated for prevention of stroke and systemic embolism, how do we switch from VKA to rivaroxaban?
VKA should be stopped and xarelto initiated when the INR =< 3.0
70
For patients treated for DVT and prevention of recurrent DVT and PE, how do we switch from VKA to rivaroxaban?
VKA should be stopped and xarelto initiated when INR =< 2.5
71
How do we switch from rivaroxaban to VKA?
both given overlapping until inr is >= 2.0
72
converting from parenteral UFH to xarelto
xarelto should be started at the time of discontinuation
73
converting from parenteral LMWH to xarelto
xarelto should be started 0-2 hours before the time of the next scheduled administration of the parenteral drug
74
converting from xarelto to parenteral anticoagulants
discontinue XARELTO and give the first dose of the other anticoagulant at the time that the next XARELTO dose would have been taken.
75
apixaban dose in stroke prevention for non-valvular AF
5mg BD, unless.....
at least 2 of the following:
- age >= 80
- weight =< 60
- SCr >= 133umol/L
THEN 2.5mg BD
76
apixaban dose in treatment or prevention of DVT
10mg BD x7d -> 5mg BD
after >=6 months or for reduction in risk of recurrent DVT following initial therapy: 2.5mg BD
77
apixaban dose in prevention of VTE after elective hip or knee replacement surgery
2.5mg BD x 35d (hip) or 12d (knee)
- starting 12 to 24 hours after the surgery
78
ddi with apixaban - increase exposure and risk of bleeding
combined p-gp and cyp3a4 inhibitors
- ketoconazole, itraconazole, ritonavir
79
how to dose adj for coadministraiton of apixaban with combined p-gp and cyp3a4 inhibitors?
for pt receiving 5mg or 10mg BD, reduce dose by 50%
for pt receiving 2.5mg BD, avoid!!
80
switching from eliquis to warfarin
discontinue eliquis, then begin both parenteral anticoagulant and warfarin at the next dose that would have been taken -> discontinue parenteral anticoagulant when INR reaches acceptable range
81
switching from warfarin to eliquis
stop warfarin and start eliquis when INR =< 2
82
what is dabigatran formulated with?
tartaric acid - reduce variability of absorption of dabigatran etexilate
83
recommended dose of dabigatran for stroke reduction in NVAF
CrCl 15-29ml/min: 75mg BD
CrCl>30: 150mg BD
84
recommended dose of dabigatran for treatment or prevention of DVT
150mg BD
- for treatment only: initial use of parenteral anticoagulation for 5-10d
85
recommended dose of dabigatran for post hip surgery DVT prophylaxis
110mg, 1-4 hours post-surgery and after achieving hemostasis -> 220mg OD for 28-35d
86
ddi of dabigatran with p-gp inhibitors
NVAF: cannot use for CrCl<30
DVT/PE & HIP: cannot use for CrCl<50
87
converting from warfarin to dabigatran
discontinue warfarin -> start dabigatrian when INR <2
88
converting from dabigatran to warfarin
start warfarin 3d (CrCL>50), 2d (30-50ml/min), 1d (15-30) before discontinuing dabigatran
89
converting from parenteral anticoagulants to dabigatran
- scheduled dosing: initiate dabigatran 0-2h before next dose
- continuous infusion (UFH): at time of discontinuation
90
converting from dabigatran to parenteral anticoagulants
CrCl>= 30: wait 12h after last dose of dabigatran
CrCl =<30: wait 24h after last dose of dabigatran
91
moa of UFH
accelerates action of antithrombin (ATIII: a naturally circulating anticoagulant antithrombin made by the liver) to inactivate various clotting factors in the coagulation cascade
- mainly factors 2a (thrombin) and 10a
- also interferes with platelet aggregation
92
does heparin cross the placenta or distribute into breast milk?
nope, it is a large molecule
93
clinical indications for UFH
- when immediate anticoagulation is required
- acute thrombotic conditions: acute DVT/PE, ACS
- when immediate reversal of anticoagulation therapy is anticipated
- prophylactic therapy when thromboembolic risks are high
94
aPTT
activated partial thromboplastin time
- reflects alterations in intrinsic pathway of the clotting cascade
- mean normal: 24-36s, varied based on reagents used for lab tests
- must wait >= 6 hours to draw aPTT after initiation of heparin
95
UFH adverse effects
- hypersensitivity: allergy to pork products
- hemorrhages (common): common sits of bleeding incl soft tissues, GI/urinary tract, nose and oral pharynx
- hyperK (rare): high or low dose, may occur as quickly as within 7 days after heparin initiation
- oseteoporosis: associated with >20,000IU/day for >= 6 months
- HIT: type 1 and 2
96
is type 1 or 2 HIT more severe?
2 - delayed onset after 5-14 days of heparin initiation, immune-mediated response
97
management of UFH overdose
1. discontinuing heparin
2. blood transfusion
3. IV protamine sulfate: bind to heparin to form stable complex, 1mg will neutralise 100U of heparin, t1/2 = 7min
98
adv of LMWH over UFH
- incr plasma half life: longer duration of action
- superior bioavailability
- lower incidence of HIT (type 1 or 2)
- less risk of osteoporosis
- more predictable dose-response rs
99
anti-Xa monitoring recommended in
- severely obese patients
- patient with renal insufficiency
- pregnant
- patients with prosthetic heart valves
- high risk for bleeding
100
use LMWH with extreme caution in patient with
indwelling epidural catheters - incr risk of spinal or epidural hematomas, resulting in permanent paralysis (BB warning)
101
aspirin MOA
irreversibly inhibit platelet COX-1 -> inhibit downstream production of thromboxane A2 (critical inducer of platelet activation and aggregation)
102
adverse effects of aspirin
upper GI events eg, gastric ulcers, GI bleeding - since cox-1 is protective of GI lining
103
clopidogrel, prasugrel, ticagrelor: which is reversible?
ticagrelor
104
prasugrel is a third gen thienopyridine, developed to __________
overcome major short comings of clopidogrel:
- large inter individual response variability (2C19 mediated metabolism to produce active metabolites)
- delayed onset of action
- high proportion of patients with insufficient inhibition of platelet aggregation
105
advantages of prasugrel and ticagrelor over clopidogrel include
reduced rates of ischemia and stent thrombosis
106
antiplatelets use in pregnancy
- clopidogrel and prasugrel: cat B, used routinely and safely
- ticagrelor: cat C, may warrant use
107
vitamin K is a ?-soluble vitamin
fat
108
2 forms of vitamin K
k1 (phylloquinone): acquired through diet and present in green leafy vege, broccoli, and brussel sprouts
k2 (menaquinone): gut bacteria, especially bacteriodes
109
vitamin D deficiency common in newborns due to
insufficient intestinal colonisation by bacteria and inadequate nutritional compensation -> parenteral vit K administered at birth
110
fibrinolysis
process of dissolution of fibrin in blood clots to prevent them from growing
111
preferred fibrinolytic drug?
tPA >>> uPA or streptokinase
- preferentially bind to clot-associated fibrin, localised PLG and tPA on the surface hence localising and enhancing plasmin generation
112
clinical uses of fibrinolytic drugs
often used following an acute ischemic stroke, MI or PE
113
absolute contraindications for fibrinolytic drugs
patients with prior cranial hemorrhage, ischaemic stroke within the last 3 months, and/or active bleeding
114
antidote for fibrinolytic drugs
anti fibrinolytic agents - tranexamic acid (competes with lysine binding sites on plasminogen and plasmin, thus blocking interaction w fibrin) - used to reverse states of excess fibrinolysis
