Venous Thromboembolisms Flashcards
where do fibrinolytics work?
convert plasminogen to plasmin
what can an arterial occlusion lead to
MI
stroke
peripheral ischemia
what can a venous occlusion lead to
DVT or PE
intravascular clot that floats within the blood
Emboli
are proximal or distal DVTs more concerning
distal DVTs due to associated w/ pulmonary embolism
what is our natural fibrinolytic that our body makes
tPA
what stabilizes the clot?
Fibrin
what dissolves the fibrin network as injury heals
Fibrinolysis
what likes to stick to clots
Cholesterol, so when the clot tries to break away it is stuck due to the cholesterol coating it
what is the extrinsic pathway for blood coagulation?
Tissue injury expressed tissue factor which complex and converts factor VII to VIIa which converts IX to IXa and X to Xa
what does Facto XA convert prothrombin to?
Thrombin which helps stabilize the clot
what removes small peptides from fibrinogen converting it to fibrin monomer which polymerizes to give the fibrin clot.
thrombin
what composes Virchow’s Triad
Venous stasis (sx, MI, varicose veins, CHF) venous endothelial injury (mechanical/ chemical) hypercoaguability (genetics)
gold standard for DVT diagnosis
Venography
what is useful in proximal DVTs
IPD (impedance plethysmography)
what can you test for in the blood that comes from fibrin-derived fragment that is released into circulation and broken down by the fibrinolytic system. Not super specific but can help rule out
D-Dimer
If non-invasive tests are negative for DVT but clinically suspicious what should you do?
Perform serial tests on days 5-7 and again on days 10-14
If noninvasive tests are negative and suspect PE what should be done?
V/Q scan
3 main medications for DVT
platelet aggregation inhibitors
anticoagulants
fibrinolytics (thrombolytics)
what are platelet aggregation inhibitors
aspirin
dipyridamole
clopidogrel
glycoprotein IIb/IIIa inhibitions
what are glycoprotein IIb/IIIa inhibitors
Abciximab
tirofiban
eptifabtide
aspirin C/I
children under 12
breast feeding
hemophilia
PUD
what must you combine dipyridamole with?
aspirin
MOA of dipyridamole
Increase cAMP levels result in decreased thromboxane A2 synthesis and thus platelet aggregation.
ADRs with dipyridamole
HA
GI bleed
Contraindications w/ aspirin
patients w/ sever HYPOTN
caustions in patients w/ serious CAD
is dipyridamole superior to aspirin alone
NO
MOA of ticlopidine
Blocks ADP-induced platelet-fibrinogen and platelet-platelet binding.
indications for ticlopidine
prevention of stroke
coronary artery stinting
C/I with ticlopidine
Liver dysfunction
blood disorders
PUD
internal bleeding
MOA of clopidogrel and ROA
inhibits activation of the glycoprotein IIb\IIIa receptor on the surface of platelets, which is required for aggregation to occur.
(oral med)
what is often added to aspirin to obtain better platelet inhibition and is safer than ticlopidine.
Clopidogrel
MOA of abciximab and ROA
antibody fragment directed towards the glycoprotein IIb/IIIa receptor of platelets. Binding & Blocking the receptor prevents platelet aggregation.
IV drug
indications for abciximab
prevention of ischemic cardiac complications in patients undergoing PCI
short term prevention of MI in patients w/ unstable angina
contraindications for abciximab
active bleeding
ADRs of abciximab
hemorrhage
N/V
HPOTN
concern with tirofiban and eptifabitide
potentially antigenic so should only be used once
MOA for heparin
Binds to antithrombin III and accelerates inactivation of coagulation factors
Binds to thrombin (inhibit activity)
binds and inhibits Factor Xa which converts prothrombin to thrombin
What does antithrombin III do?
Inhibits the binding of fibrinogen to thrombin and hence is an anticoagulant
what does Low molecular weight heparin inactivate?
Factor Xa (doesn't bind as well to thrombin)
what is the route of administration for low molecular weight heparin?
Sub Q
Does heparin cross the placenta?
No, so ideal to use in pregnancy
contraindications with low molecular weight heparin
hemophilia
thrombocytopenia
PUD
for low molecular weight heparin should it be used with kidney disease?
very cautiously, don’t use if CrCl is under 30
how do you reverse bleeding with heparin/ LMWH? (not as good with LMWH)
protamine 1 mg for every 100 U of heparin given in previous 4 hours
what is a big side effect with heparin that is associated with arterial or venous thrombosis in 60% of patients.
Heparin-induced thrombocytopenia (HIT)
when does the platelet count drop with HIT?
5-15 days after treatment
reduction of >50% from baseline or platelets <100,000
what can some complications of HIT
DVT
pulmonary embolism
stroke
end organ damage
If a patient develops HIT what can you switch to?
DTIS (argotroban or lepirudin) then try to switch over to warfarin once platelets >100,000
where does lepirudin come from?
Leech spit
who is osteoporosis seen in with heparin use?
pregnancy
Labs to see how well heparin is working?
aPTT (q 6 hours until stable) then daily
PT/INR
CBC (every other day x 14 days )
with LMWH what other lab do you add besides the ones your check for heparin?
SrCl
anti factor Xa activity
what is an indirect factor Xa inhibitor? It is for prevention of DVT and tx of DVT? PE
Fondaparinux (SQ)
when is fondaparinux contraindicated?
CrCl <30 ml/ min
what cofactor is needed for fondaparinux?
anti-thrombin III
what is an oral med indicated in prevention of DVT in patients undergoing knee or hip replacement surgery. Stroke and systemic embolism prophylaxis in patients with non-valvular a fib
Rivaroxaban
Indicated for DVT prophylaxis in patients post hip and knee replacement
Oral
Not recommended in CrCl < 15mL/min or severe liver failure (Child-Pugh class C)
Apixaban
what is a direct thrombin inhibitor that is taken orally. Directly inhibits thrombin (free and clot bound). Reduces risk of stroke in those w/ a-fib. Dose adjust for CrCl < 30 ml/min
Dabigatran
Direct thrombin inhibitor used in heparin-induced thrombocytopenia w/o thrombosis, possibly ischemic stroke, hemodialysis, percutaneous coronary internvetion.
Argatroban
is there an antidote for direct thrombin inhibitors
no
Direct thrombin inhibitors dervied from leech. They inactivate thrombin and used in people with HIT and prophylaxis of DVT in patients undergoing hip and knee replacement.
Desirudin
Lepirudin
Works as a vitamin K antagonist and has lots of drug interactions (P450). Oral med
Warfarin
what is warfarin used for?
acute MI
prophylaxis of DVT, PE, a-fib emboli, rheumatic dz emboli, prosthetic heart valves, emboli in patients with hip or knee replacement
Contraindications with warfarin?
cerebral thrombosis
peptic ulcer
pregnancy
Antidote for warfarin
Vitamin K (takes up to 24 hours)
ADRs with warfarin
bleeding
skin necrosis
labs to monitor with warfarin
baseline PT/INR, aPTT, CBC, LFTs
yearly CBC
urinalysis and fecal occult PRN
How often is PT/INR checked?
Every 2-3 days initially until INR in therapeutic range x 2 then can spread out monitoring time
What is the therapeutic dose for warfarin?
2-3
other sources of vitamin K?
green tea
leafy green vegetables
What are thrombolytic (fibrinolytic) agents?
Alteplase
streptokinase
anistreplas
urokinase
What is the mechanism of thrombolytic agents?
turns plasminogen to plasmin (which cleaves fibrin, thus lysing thrombi)
clots are more resistant to lysis as they age
what are thromoblytic agents often co-administered with?
antiplatelet or anticoagulant
when are thrombolytic agents used?
MI- intracoronary is possible (or iV)
massive PE w/ hemodynamic compromise
heparin treatment failures
extensive proximal DVT
ADRs of thrombolytic agents
hemorrhage
reperfusion arrhythmias
contraindications for thrombolytic agents?
recent surgery/ trauma w/i 7-10 days CVA within 2 months recent needle puncture of noncompressible vessels (epidural) actie bleeding uncontrolled HTN malignancy (will clot a lot) Pregnancy CPR
what is a tissue type plasminogen activators (TPA) that works by catalzyeing the conversion of tissue plasminogen to plasmin in the presence of fibrin.
Alteplace
when is alteplase indicated?
acute MI
PE
Acute ischemic stroke
ADRs of alteplase
bleeding
arrhythmias (monitor ECG)
N/V
cardiac arrest, stroke, thromboembolism
thrombolytic agent dervied from culture broths of Group C Belta hemolytic streptococci.
Streptokinase
MOA of streptokinase
Forms 1:1 complex w/ pasminogen to conver the active enzyme plasmin
hydolysis fibrin plugs
indications for streptokinase
life-threatening DVT
PE
arterial thromboembolism
acute MI
ADRs of streptokinase
N/V
bleeding
antigenic- allergic rxns (rash, fever, anaphylaxis)
tx for acute DVT of a leg if confirmed
short term therapy with LMWH or IV unfractionated heparin or SC fondaparinux
what other drug do you start with DVT?
warfarin, wait for it to be therapeutic (about 5 days)
if a person with DVT with a CrCl < 30 what should be used?
UFH over LMWH
with patients with proximal DVT what can you do?
Catheter directed thrombolysis (CDT)
should patient with a DVT be placed on initial bed rest or early ambulation?
early ambulation
tx for confirmed PE
LMWH
IV UFH
SC fondaparinux
if a patient has non-massive PE is LMWH or UFH preferred?
LMWH
In a massive PE what is recommended- UFH or LMWH
UFH
if there is a high clinical suspicion of PE what is the recommended tx?
anticoagulants while waiting outcome of diagnostics
what other drug should be initated with anticoags with PE?
warfarin
when should you use thrombolytics with a PE?
without HPOTN
low risk bleeding
(majority of patients with PE wont’ reiceve thrombolytics)
what is long term tx for DVT/ PE?
Warfarin for 3 months (secondary to transient risk)
if more risks- continue therapy
for low risk patients (for VTE) what is the recommendation?
early ambulation
for moderate risk patients (for VTE) what is the recommendation?
ES (stockins)
IPC (pressure compression)
Low dose UFH
LMWH
for higher risk patients (for VTE) what is the recommendation?
IPC
low dose UFH
LMWH alone or w/ ES or IPC
for very high risk patients (for VTE) what is the recommendation?
LMWH
low dose UFH
factor Xa inh combined w/ IPC. ES
for a total hip replacement what should a a patient be placed on for DVT/ PE prevention
LMWH
Warfarin (INR 2.5)
Factor Xa inh
for total knee replacement what should a a patient be placed on for DVT/ PE prevention
LMWH
Warfarin
Factor Xa inh +/- IPC
for hip fracture surgery what should a a patient be placed on for DVT/ PE prevention
Factor Xa inh
LMWH
warfarin
LDUH
