Cardiovascular Medications related to Blood Products: Part II

what does an arterial thrombosis pertain to?

platelet aggregation and plaque rupture

what are arterial clots mostly made up of?

platelets and thrombin; they CAN contain leukocytes too

what does a venous thrombosis pertain to?

Virchow's Triad; RBCs and platelets form a thrombus when the clotting cascade is initiated

what are venous clots mostly made up of?

fibrin and erythrocytes; they CAN contain platelets too

what is Virchow's Triad?

the three factors that cause thrombosis developed by Rudolf Virchow

what are the three factors that cause thrombosis in Virchow's Triad?

1. venous stasis

2. endothelial damage

3. hyper-coagulable state

what drugs would we want to use if we had a patient with an arterial clot (generally speaking)

those that prevent platelet activation and/or dissolve fibrin

what drugs would we want to use if we had a patient with a venous clot (generally speaking)

drugs that prevent fibrin and/or thrombin

what do anticoagulants do?

suppress fibrin formation

what type of clots do anticoagulants focus on?

venous clots

what do antiplatelets do?

inhibit platelet aggregation, making them less "sticky"

what type of clots do antiplatelets focus on?

arterial clots

what do thrombolytics do?

break up fibrin, thus dissolving the thrombi/clots

what are examples of anticoagulants?

heparin and warfarin

what are examples of antiplatelets?

aspirin and tirofibran

what are examples of thrombolytics?

alteplase and streptokinase

does heparin act on bound or non-bound thrombin?

non-bound only; doesn't act on bound thrombin

which factor is the start of the common pathway?

factor Xa

does heparin dissolve clots?

no! it stops thrombosis to proactively prevent clots, however once the clot is formed, heparin doesn't work

where does heparin act?

in the first three steps of the clotting cascade

heparin uses

rapid anticoagulation (DVT, PE)

what do we do after a patient has been on heparin for several days?

we convert them to oral anticoagulants

is low molecular weight heparin or unfractionated heparin better?

it all depends on the situation of the patient, however low molecular weight heparin is generally better for use because it has less risks, less lab monitoring, and is safe to administer at home

what are low molecular weight heparins used to do?

prevent thromboembolism after surgery

heparin ADRs?

bleeding, hemorrhage, heparin-induced thrombocytopenia

what must you do if you inspect any bleeding of a patient on heparin?

you must report to the provider if ANY bleeding occurs; it might mean they need a different drug to stop the bleeding if it's bad; you would then check aPPT after a few hours to see if the bleeding has become controlled

what is an ADR for any medication that causes blood thinning?

bleeding and hemorrhage

what do we monitor when a patient is on heparin?

aPTT (activated partial thromboplastin time)

what is the normal aPPT for a patient?

40

what is the goal aPPT for a patient on heparin?

1.5-2.0x the control amount; therefore clotting time should be 60-80 seconds

what must you do if the aPPT of a patient on heparin is much higher or much lower than 1.5-2.0x the normal level?

page the provider as this could be a dangerous situation; you might need to hold the med and administer the antidote

what is the antidote to heparin?

protamine sulfate

what is heparin-induced thrombocytopenia?

paradoxical development of thrombi; increased resistance to anticoagulation effects of heparin

what could heparin-induced thrombocytopenia result in?

loss of limb or death

what is a hemorrhage?

progressively falling platelet count

what are the low molecular weight heparins you need to know for this exam?

- enoxaparin

- dalteparin

how are low molecular weight heparins administered?

subcutaneous

what is another word for prevention?

prophylaxis

what characteristics make a low molecular weight heparin?

- smaller/shorter molecules

- fixed dose

- subQ admin

- administered at home

what type of drug is warfarin?

PO anticoagulant

what is unique about warfarin?

it is the oldest known anticoagulant; it was originally used in rat poison, but under monitored and controlled doses, it has beneficial uses for humans

what does warfarin do?

inhibit blood clots by interfering with vitamin K clotting factors

which factors are vitamin K dependent?

7, 9, and 10

what is warfarin used for?

prophylaxis of TIAs, MI, long term anticoagulation(preventing venous thrombosis, pulmonary embolism, heart valve thrombus), and A-Fib

does warfarin have a rapid or delayed onset?

delayed because it takes time; 4-5 day delay until all existing factors in circulation are depleted

why is vitamin K important?

it helps form clotting proteins

what do blood clotting proteins do?

hold blood cells together to form clots

what happens when we lower clotting protein levels?

blood clots are less likely to occur

warfarin ADRs

bleeding

warfarin interactions

protein binding; higher affinity, meaning it will bind more

warfarin antidote

vitamin K by injection, not PO

how do we monitor patients on warfarin?

monitor PT; the control is about 12 seconds

we also monitor the International Normalized Ratio (INR)

what are the goals for a patient on warfarin?

2-3x the norm in INR and PT for most patients, 3-4.5x in special situations -- this translates to about 24-36 seconds

what must you do if you see bleeding in patient that is on warfarin?

you MUST record and report the bleeding to your provider, even if they are within the therapeutic range

what must you do if the patient on warfarin is above/below the threshold?

talk to the provider

which anticoagulant should you use in an emergency? why?

heparin > warfarin; heparin is rapid, whereas warfarin is delayed

what do patients need to know about taking warfarin?

do not overdo it on the vitamin K foods (such as leafy greens); keep it consistent if you do regularly eat them

what is the direct reversible inhibitor of thrombin you need to know for this exam?

- dabigatran (it has bi in the name; bi = two and dabigatran activates factor 2)

how is dabigatran and heparin different?

heparin converts fibrinogen to fibrin

dabigatran PREVENTS the conversion of fibrinogen to fibrin by inhibiting both types of thrombin (bound and free)

how is dabigatran better over warfarin?

dabigatran has a rapid onset and there is no need to monitor the blood values; there are fewer drug-food interactions and there is a lower risk of bleeding; also, dosage is uniform across age/weight

what is dabigatran approved for?

a-fib and post-op use

dabigatran ADRs

bleeding, GI pain, diarrhea, dyspepsia

dabigatran antidote?

idarucizumab or hemodialysis

what do direct reversible inhibitors of thrombin activate?

factor 2

what are NOACS?

newer oral anti-coagulants

what are DOACS?

direct oral anti-coagulants

what direct (selective) factor Xa inhibitor do you need to know for this exam?

- rivaroxaban (easy to recognize bc it literally has Xa in the name)

- apixaban

what are the benefits of rivaroxaban?

rapid onset, fixed dosage, fewer drug drug interactions

type of anti drug is rivaroxaban?

an anti-thrombotic

what do anti-thrombotics do?

block the action of factor Xa and inhibits thrombin production

advantage of rivaroxaban over warfarin?

rivaroxaban is rapid onset whereas warfarin is delayed

rivaroxaban risks?

bleeding and some med interactions

when seeing a pregnant woman or renally impaired patient, would rivaroxaban be your DoC?

no; you should only use it on these patients with great caution; it's better to use heparin first

when do we use rivaroxaban on pregnant/renally impaired patients?

only when the benefits > risks

hepatic factors when taking rivaroxaban? what causes this?

risk of bleeding is increased; this is due to delayed excretion, therefore having higher levels of Xa

what is the antidote to rivaroxaban?

andexonate alfa

what type of drug is apixaban?

another direct inhibitor of factor Xa

what does apixaban prevent?

stoke and systemic embolism in pt. with a-fib

why must we caution use of apixaban in renally impaired patients?

decreased excretion levels may lead to higher drug levels, therefore we would use renal dosing bc the dose would be decreased

apixaban antidote?

andexanet alfa, however it was rejected in 2016 then approved again in 2018 out of necessity

patient teaching when taking a direct inhibitor of factor Xa?

- consistent intake of vitamin K (no binges of vitamin K high foods)

- avoid IM injections to decrease bleeding risk and formation of hematoma

- if you fall, you need to be assessed

- avoid ASAs, NSAIDs, and alcohol because they thin the blood

- carry ID around

what anti-platelet agent do you need to know for this exam?

- ASA (aspirin)

how do we dose aspirin?

either as low dose of 80mg or a high dose of 325mg as a prophylaxis

how does aspirin work?

it interferes with platelet ability to adhere to each other by irreversible inhibition of cyclooxyrgenase (COX)

what happens to platelets that are born into a body with ASA in it?

it will be subjected to COX for its entire lifespan, meaning they will never be able to clot

is aspirin reversible?

the EFFECT ON PLATELETS is not reversible, however we can REVERSE THE DRUG ITSELF out of the patient by discontinuing it

what uses do we have for aspirin?

- ischemic stroke

- TIA

- stable and unstable angina

- coronary stenting

- acute and previous MI

- MI prevention

what are the P2Y12 ADP Blocker you need to know for this exam?

- clopidogrel

- ticagrelor

what does clopidogrel do?

prevents platelets ability to adhere; this is irreversible -- also used to prevent blockage in post stent pt

what is clopidogrel usually combined with?

a low dose ASA to create a full effect of P2Y12 receptor blockage while keeping the platelets slippery

what is clopidogrel usually given with to prevent gastric bleeding?

a PPI

is clopidogrel a pro-drug?

yes! therefore for it to work it needs to be metabolized first

what do P2Y12 ADP Blockers do?

they block P2Y12 Receptors

what is ticagrelor included in?

the STEMI guidelines

what is ticagrelor used for?

prevention of thrombosis in acute coronary syndromes

what kind of effects does ticagrelor have that clopidogrel does not?

reversible effects!!

what is ticagrelor usually combined with?

a low dose ASA

is ticagrelor a prodrug?

nope! it activates upon administration

what does ticagrelor reduce the risk of?

MI, CVA, and death

what risk does ticagrelor present?

bleeding, specifically intracranial bleeding (ICB)