Medications: Antithrombotics Flashcards
(54 cards)
1
Q
MOA: interacts with antithrombin III to inactivate factor Xa and inhibits the conversion of prothrombin to thrombin (IIa)
* also IXa, Xla, and Xlla
A
Unfractionated Heparin (UFH)
2
Q
- variable response due to binding plasma proteins
- relatively short t1/2 at therapeutic doses (about 60 minutes)
- not absorbed orally- IV medication
- route of adminsitration- IV or subcutaneous
A
unfractionated heparin
3
Q
what are some indications for unfractionated heparin?
A
- treatment of acute venous thromboemoblism (VTE) and pulmonary embolism
- acute MI and unstable angina
- VTE prophylaxis
- disseminated intravascular coagulation
4
Q
what does activated partial thromboplastin time (aPTT) used for monitoring unfractionated heparin measure?
A
- measures activities of thrombin and factor Xa
- monitor theraputic doses of UFH
- goal: 1.5- 2.5 times control
5
Q
what labs are used to monitor unfractionated heparin?
A
- chromogenic antifactor Xa heparin assay
- activated clotting time (ACT)- higher doses given to pts undergoing PCI and CABG
- activated partial thromboplastin (aPTT)
- CBC
6
Q
What are adverse effects of unfractionated heparin?
A
- bleeding: increased by higher dose, concomitant adminstration of fibrinolytic agents of GPIIb/IIa inhibitors, recent surgery/ trauma/ invasive procedure, hemostatic defects
- osteoporosis- more for longstanding use
- increased LFTs
- heparin induced thrombocytopenia (HIT)
7
Q
- prothrombotic condition associated with increased thrombin
- caused by heparin dependent antibodies
- typically occurs 5-10 days after initiation of heparin
- consider when: platetes decrease by >50% and or throbotic event occurs in patients treated with heparin
A
Heparin induced thrombocytopenia (HIT)
8
Q
if you suspect HIT, what laboratory testing should be done?
A
- Ag assays that detect presence of HIT antibodies
- functional assays that detect evidence of platelet activation (by HIT Ab) in presensce of heparin
9
Q
what are the 4Ts probablitity score for HIT? what do the scores mean?
A
- Thrombocytopenia
- timing of platelet count fall
- thrombosis (or other clinical sequelae)
- other cause of thrombocytopenia
- 0-3 points = low probablilty
- 4-5 points = intermediate probabilty
- 6-8 points = high probability
10
Q
treatment of HIT?
A
- stop all forms of heparin (including flushes and LMWH)
- Avoid warfarin until platelets recover
- treatment options: lepirudin, argatroban, bivalirudin
- fondaparinux
11
Q
How do you REVERSE unfractionated heparin?
A
- stop heparin
- protamine sulfate
12
Q
dosing of protamine sulfate? what should you note?
A
- if 1mg neutralizes approx. 100 units of heparin
- if 30 minutes have elapsed can give 1/2 dose
- if >2 hours have elapsed, can give 1/4 dose
- maximum of 50mg
note
* monitor aPTT
* adverse effects: hypotension, bradycardia
* avoid in patients with fish allergies
13
Q
MOA: similar to UFH, except less activity against IIa relative to Xa
A
Lower molecular weight heparin
14
Q
what medications are LMWH?
A
enoxaparin
dalteparin (brand only)
15
Q
what are indications of LMWH?
A
- VTE prevention- post surgery, restricted mobility due to acute illness
- treatment of acute VTE and PE
- treatment of unstable angina or non-Q wave MI
- treatment of STEMI
- Treatment of VTE in cancer patients long term
16
Q
for prophylactic dosing which antithrombotic is preferred when there is renal impairment? LMWH OR UFH?
A
Unfractionated heparin is preferred
17
Q
what labs should be monitored when using LMWH?
A
- Anti-factor Xa level (routine monitoring not indicated ; montitor obese patients, renal insufficiency, pregnancy measure peak (for enoxaparin- 4hrs after dosing)
- platelets
- CBC
- Renal function
- weight
18
Q
what are some adverse effects of LMWH?
A
injection site- pain, brusing
19
Q
how do you reverse LMWH?
A
no proven method for reversal
protamin partially neutralizes
20
Q
how do you dose protamine in reversal of LMWH?
A
- <8 hours: 1mg protamine per 1mg enoxaparin
- 0.5mg protamine per 1mg enoxaparin should be administerd if bleeding continues
- smaller doses of protamine can be give if the time since LMWH administration is >8 hours
21
Q
MOA: indirect factor Xa inhibitor
renally cleared- dose adjust for renal impairment
A
fodaparinux
22
Q
what are indications of Fondaparinux?
A
VTE prophylaxis
23
Q
Adverse effects of fondaparinux?
A
bleeding
injection site reaction
24
Q
Adverse effects of fondaparinux? What should you monitor?
A
- bleeding
- injection site reaction
monitoring:
* CBC, Anti factor Xa, renal function
25
MOA: inhibits Vitamin K epoxide which blocks the synthesis of vitamin K-dependent clotting factors; also inhibits synthesis of protein C and S
* II, VII, IX, X
Warfarin
26
what is the effect of warfarin on an established thrombus?
no direct effects on established thrombus
* prevents further extension of clot
* prevents secondary thromboemolic complications
* prevents recurrent thromboembolic event
27
How should use of warfarin be monitored?
international normalized ratio (INR)
* hospitalized patients: usually daily
* outpatients: every 2-3 days until stable
* then q1 week, q2 weeks, q4 weeks
* CHEST guidlines for consistently stable INRs
CBC
* at least every 6 months
28
what are some contraindications of warfarin?
* active or recent CNS bleeding
* hemorrhagic tendendices or blood dyscrasias
* pregnancy
* trauma or sever bleeding
* alcoholism
* significant hx of falls or fall risk
* recent/anticipated neurosurgical, cerebrospinal or eye surgery
29
which medications when used with warfarin increase the risk of bleeding?
* antiplatelets
* NSAIDs
30
what are adverse effects of warfarin?
Bleeding
* less sever: bruising, epistaxis, gum bleeding
* more severe: GI bleeding, ICH
Other
* skin necrosis
* purple toes syndrome
* teratogenicity
31
what labs should be done before starting warfarin?
* INR
* CBC with plateltes
* LFTs
* pregnancy test
32
What are some reasons for subtheapeutic INR?
* nonadherence
* large amounts of vitamin K
* wrong strength
* ran out of medication
* drug/diet interaction
* follow up too soon to see effect
33
reasons for a supratherapeutic INR?
* nonadherence
* lower amounts of vitamin K than normal
* wrong strength
* excessive alcohol intake
* drug/diet interaction
* poor nutritional intake
* acute illness
34
how should you treat subtherapeutic INR?
increase weekly dose
consider boost (one-time extra dose)
35
how should you treat supratherapeutic INRs?
decrease weekly dose
consider one time dose omission
36
How can Warfarin be reversed?
* stopping warfarin (about 4-5 days for INR to return to baseline)
**vitamin K**
* oral - may take up to 24 hours to see full effects
* IV: given in hospital; IV route preferred over SQ
Fresh frozen plasma (FFP)
factor VII
Prothrombin complex concentrates
37
treatment for patients with an INR above therapeutic range but <4.5 with no evidence of bleeding?
lower or omit dose
* monitor more frequently and resume lower dose
* only if minimally elevated, no dose reduction needed
38
treatment for patient with INR >4.5 but <10.0 with no evidence of bleeding
Omit 1-2 doses, monitor more frequently and resume appropriate adjusted dose when INR therapeutic
| Routine use of VITAMIN K not recommended
39
treatment for INR > 10 no evidence of bleeding
hold warfarin therapy and give vitamin K (2.5-5mg)
resume at appropriate adjusted dose when INR is therapeutic
40
treatment for serious bleeding at any INR elevation?
hold warfarin and give vitamin K (5-10mg) by slow IV infusion supplemented with PCC, FFP, or rVIIa
41
what medications are direct oral anticoagulants?
dabigatran
rivaroxaban
apixaban
edoxaban
42
What are reversal agents of direct oral anticoagulants?
Idaracizumab
adexanet alfa
43
MOA: Humanized monoclonal Ab fragment that binds to diabigatran with an affinity; binds specifically to free and thrombin bound dabigatran
When do you see reversal?
Idarucizumab
* 4 hours
44
MOA: recombinant modified human factor Xa protein
Black box warning: thromboembolic risks, ischemic risks, cardiac arrest and suddent deaths
andexanet alfa
45
which medications does andexanet alfa reverse?
rivaroxaban
apixaban
edoxaban
46
what are benefits of DOACs?
fast onset/offset
fixed dosing
limited monitoring
more equal effectiveness
less major bleeding
47
which DOAC is a direct thrombin inhibitor?
dabigatran
48
which DOAC is a factor Xa inhibitor?
rivaroxaban
apixaban
edoxaban
49
What are some blackbox warnings for DOACs?
* stopping prematurely can increase ischemic events or clot
* if discontinued, consider using another anticoagulant
* epidural/spina hematomas and spinal procedures
50
For treatment of VTE, what DOACs can be used regardless of high BMI and weight?
rivaroxaban or apixaban
51
How do you reverse warfarin?
phytonadione
PCC (prothrombin complex concentrate)
52
How should you assess bleeding risk? what is the acronym?
* **H**ypertension
* **A** bnormal renal and liver function
* **S**troke
* **B**leeding tendency or predisposition
* **L**abile INR
* **E**lderly (greater than 65 years old
* **D**rugs (concamitant aspirin or NSAIDs or excess alcohol use
53
duration of anticoagulation therapy if the clot is provoked?
transient/temporary risk factor
* complete anticoagulation after finishing primary treatment (3-6 months)
chronic risk factor
* continue anticoagulation indefinitely for secondary prevention after primary treatment
54
duration of therapy if a clot was unprovoked?
* continue anticoagulation indefinitely for secondary prevention after primary treatment
