Anticoagulation Therapy Flashcards
what is the first line of tx for sickle cell & what is the goal of therapy?
Hydroxyurea
- reduce episodes of pain
- reduce hospitalizations
what is the dosing frequency for Hydroxyurea and what is the time frame for clinical response??
QD PO - weight based
> slow therapeutic response ~ 3-6 months
what is the second line of tx for sickle cell and what are other treatments?
Second Line Tx: L-Glutamine (Endari): amino acid
- monoclonal antibodies: Clavizunab
- blood transfusions
- stem cell transplant
what anticoag blocks vitamin K and requires PT/INR monitoring?
Warfarin (Coumadin)
what is a naturally occurring anticoagulant that inactivates thrombin and factor Xa?>
Heparin
what new anticoagulants are considered pure factor Xa inhibitors?
Rivarobaxan (Xarelto)
Apixaban (Eliquis)
what AC is a direct thrombin factor and what does it act on?
Dabigatran (Pradaxa) -> inhibits thrombin (factor IIa)
what are clinical indications for Warfarin?
Afib -> PT/INR monitoring monthly
prophylactic or treatment of DVT & PE
what are common side effects of Warfarin & which are the most worrisome?
fever rash diarrhea hepatitis *** hematuria -> indication of internal bleed *** hemorrhage
what is the dosing regimen for Warfarin and when must INR be monitored?
- Initiation: 2-5mg qd x2-4 days
- Check INR after 2nd or 3rd dose
- Adjust dose based on PT/INR
- After INR stabilizes, check INR BIW
- INR checked monthly once therapeutic
in what patients must you caution when they are prescribed warfarin?
elderly -> fall risk
patients w/ renal or hepatic failure -> more sensitive, watch CYP450
what is the goal INR for warfarin?
therapeutic range: 2-3
goal: 2.5
if a patient’s INR is > 3, what should be done?
hold Warfarin and recheck INR levels
how many days does it take for warfarin to stabilize?
5-6 days
what is the maintenance dose for warfarin?
2-10mg qd
what is a rare reaction to warfarin that is seen in patients with protein C or S deficiency?
“purple/blue toes syndrome”
|»_space;> due to microembolization of cholesterol, which occurs after several weeks to months of therapy
aside from vitamin K, what is used for reversal of warfarin?
fresh frozen plasma
what are drug interactions for warfarin & why does this happen?
Amiodarone
Alcohol
Cimetidine (Tagamet)
Disulfiram
Abx: Macrolides, tetracyclines, quinolones
Phenylbutazone
»> all are metabolized by Cytochrome P-450 system
what drugs may increase INR levels in patients on warfarin?
Cephalosporins Tetracyclines- Doxycycline Fluoroquinolones Macrolides Bactrim Glucocorticoids Omeprazole
what drugs may decrease INR levels in patients on warfarin?
PCNs Vitamin K Carbamazepine Phenobarbital Dilantin/Phenytoin
what are drug interactions for Heparin that may cause an additive AC effect?
PO anticoags
Salicylates & other antiplatelet drugs
> ASA
> NSAIDs: Ibuprofen, Naproxen
what drug-herb can increase the risk of bleeding for heparin?
horse chestnut
what are clinical indications for unfractionated Heparin and what is the major side effect?
DVT, PE, VTE prophylaxis
|»_space;> Hemorrhage
what is the MOA for unfractionated Heparin?
binds to antithrombin III -> inactivating factors IIa, IXa, Xa, XIa, and XIIa = thrombin complex
» fibrinogen goes not convert to form fibrin
does the dose need to be adjusted for unfractionated Heparin in patients with renal insufficiency or
renal failure?
no (therapeutic doses)
what is the half life of unfractionated Heparin and why is this important?
1-2 hours -> dose-dependent and may be disproportionately prolonged at higher doses
*requires aPTT monitoring
what are adverse reactions for unfractionated Heparin?
#1: hemorrhage thrombocytopenia (HIT) white clot syndrome anaphylaxis fever
what is the tx of choice for VTE prophylaxis in patients with HIT?
Fondaparinux (Arixtra)
what can happen to a patient with HIT if they are given unfractionated heparin?
antibodies to platelets -> triggers thrombin generation -> venous or arterial thrombosis
what is the reversal used for unfractionated Heparin?
Protamine Sulfate
what are contraindications for Protamine Sulfate?
Hypersensitivity Any bleeding disorder Surgery of brain, eye, or spinal cord Intracranial Hemorrhage Infective Endocarditis Hx of HIT
what is the route of administration for unfractionated heparin and why is this important?
IV or SC -> hospital settings
> cheaper
> closer monitoring of aPTT
what is the dose for prevention of PE for unfractionated heparin?
5,000 units SC q 8 to 12 hours
*weight based when starting
what are the most common low molecular weight heparins (LMWH) and what is the freq of dosing?
Enoxaparin (Lovenox)
Dalteparin (Fragmin)
what are the advantages for using LMWH?
increased bioavility d/t long half life
-decreased chance of induce thrombocytopenia
-more predictable -> lab monitoring is not required
*** outpatient therapy
> preloaded syringe
what do LMWH primarily act on?
factor Xa - same as heparin but less binding
when is Lovenox indicated?
prevention of DVT, PE
why is Fondaparinux (Arixtra) used in patients with HIT (think of MOA)?
it is a synthetic selective factor Xa inhibitor with no antithrombin activity
» administered IV drip qd
what must be considered when dosing Fondaparinux (Arixtra)?
renal dosing
»> CrCl 30-50 caution is advised
***** CrCl < 30 contraindicated
why must a patient be started on Warfarin at least 5 days before discontinuing Heparin for outpatient treatment?
due to need for 5 day monitoring which allows warfarin to achieve full therapeutic effect
how are the DOACs get metabolized and what is their mechanism of action?
DOACs: Apixaban & Rivaroxaban
Metabolized in liver
» directly inhibits factor Xa
what is the reversal for Apixaban and Rivaroxaban?
Andexxa
disadvantage: only available in hospital and is very expensive
what should you do if a pt on a direct oral anticoagulant starts to have bleeding and does not have access to Andexxa?
discontinue dose of DOAC
what are the advantages of direct oral anticoagulants over UFH & LMWH (vitamin K anticoagulants)?
PO administration
onset: rapid
predictable therapeutic effect-> no routine PT/INR
*** short half-life
how many days must a DOAC be held prior to surgery?
3 days
* as opposed to 5 in LMWH & UFH
what are the disadvantages of new oral anticoagulants over VKAs?
- no routine coag monitoring -> no awareness if pt is noncompliant and cannot titrate dose
- short half-life -> less efficacy in non-compliant patients
- antidotes are very expensive
- may need dose adjustment for renal or hepatic dysfunction
what is the maintenance dosing for Apixaban (Eliquis)?
5mg BID PO
what is the VTE prophylaxis dose for Apixaban?
2.5mg BID
what is the maintenance dose for Rivaroxaban (Xarelto)?
20mg QD
What is the maintenance dose for Dabigatran (Pradaxa)?
150mg BID
In all newer oral anticoagulants, what must be considered?
renal dosing -> must check CrCl
if an 80 y/o M w/ afib weighs less than 60kg and has a Creatinine of 1.5, what should be done to their maintenance Eliquis dose?
- reduce Eliquis to 2.5mg BID
OR - switch to Xarelto
what is considered in dosing Apixaban/Eliquis for afib patients?
age »_space;»> 80
weight ««_space;60 kg
Creatinine»_space;»/= 1.5
*if pt has 2 out of 3 criteria -> must reduce dose to 2.5mg BID OR switch to Xarelto
what are the interactions for Apixaban (Eliquis)?
amiodarone antiplatelet meds carbamazepine phenytoin azole antifungals diltiazem rifampin macrolides: clarithromycin, erythromycin
in what situations would DVT prophylaxis be considered in starting temp anticoagulation therapy with Apixaban?
s/p TKR or total hip replacement
What are other newer anticoagulants indicated for stroke prevention and embolus with non-valvular afib?
Edoxaban (Sayvasa)
Betrixaban (Bevyxxa)
what is the maintenance dose for Dabigatran (Pradaxa) & what must be considered in patients?
150mg BID
-renal function
what is the MOA for Dabigatran (Pradaxa) and major side effect?
inhibits factor IIa
-bleeding
what is the reversal for Dabigatran (Pradaxa) & what is the benefit and disadvantage for it?
Praxbind/Idarucizumab
benefit: 100% immediate effect
con: very expensive
when initiating therapy of Rivaroxaban (Xarelto) for patients, what must you counsel them on?
increased risk for bleeding
|»_space; must take w/ food
if switching a pt currently on Warfarin to Apixaban/Rivaroxaban, how should this be done?
discontinue warfarin and when INR is at 2, start Apixaban
*if INR < 2 -> can start right away
if switching a pt currently on Apixaban or Rivaroxaban to Warfarin, how should this be done?
start warfarin w/ 2-3 day overlap
-when INR is therapeutic on Warfarin, OK to d/c Xa inhibitor
when switching a pt currently on Heparin to direct oral ACs, is there overlap when starting?
no
