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1. Prothrombin --->?
2. What factor is PT?
3. What activate PT?
Prothrombin ---> Thrombin
PT (factor II) ---> Thrombin (factor IIa)
Factor Xa activates PT
What are the 3 drugs that bind to antithrombin III (AT)?
- Fondaparinux (Arixtra)
What are 3 drugs (SC and PO) that inhibits Factor Xa?
- SC - Fondaparinux (Arixtra)
- SC - Enoxaparin (Lovenox)
- PO - Rivaroxaban (Xarelto)
What is the only oral DTI available currently?
What is the drug class of choice for HIT?
Injectable DTI's (Argatroban, Lepirudin)
Heparin blocks which coagulation pathway?
Intrinsic pathway (contact activation, damaged surface activated)
What is the therapeutic aPTT/PTT for heparin?
How often do you check aPTT until therapeutic?
Check before initiation, check every 6 hours until 2 therapeutic readings. Then check
What are the dosage forms of heparin?
1000 units/ml, 2500 units/ml, 5000 units/ml, 7500 units/ml, 10,000 units/ml, 20,000 units/m
What specific labs should be monitored for heparin? (3) Why?
Monitor for bleeding and HIT
When do you dose-adjust renally for heparin?
No renal dose-adjustments
What is the PTT goal for heparin subc?
PTT unaffected so not monitored
What is the alternative for warfarin in pregnant women?
Heparin - large molecule that doesnt cross
What is the VTE prophy dose for heparin? Where can you administer?
5000-10,000 units subc q8-12hrs
Inject in lower abdomen, inner thighs, or upper arms
What are the 3 G herbs that increase risk of bleeding?
Ginger, garlic, ginkgo biloba
(ginseng decreases INR with warfarin)
When does HIT usually occur with heparin use?
How much would PLTS have to drop from baseline to be considered as thrombocytopenia?
HIT occurs 5-14days usually after initiation of heparin
PLT drop >50% from baseline = thrombocytopenia
How does HIT occur in heparin use? What if it is left untreated?
Immune system forms IgG antibodies against heparin when it binds to platelet factor 4 (PF 4). IgG + heparin + PF 4 forms a complex that binds to platelets, leading to platelet activation and thus a pro-thrombotic state.
If untreated, may lead to venous/arterial thrombosis and amputations, post-thrombotic syndrome, and/or death
For HIT, what is the DOC for pts with renal impairment? Hepatic impairment?
What is the DOC for pts with urgent cardiac surgery or PCI?
- Renal impairment = argatroban
- Hepatic impairment = lepirudin
- Cardiac surgery or PCI = bivalirudin
For HIT pts, when would you initiate warfarin?
When PLT at least 150,000/mm3, overlap with nonheparin anticoagulant for a minimum of 5 days
What is the antidote dose for heparin and LMWH overdose? Max dose?
1mg protamine for 100 units heparin
Max dose 50mg
1mg protamine for 1mg enoxaparin
What is the treatment dose for VTE for heparin?
What type of weight would you use for dosing?
80units/kg IV bolus followed by 18units/kg/hr infusion OR 5000units IV bolus followed by 1000units/hr infusion
Use actual body weight
What are 5 main s/e of heparin? (including 1 long-term s/e)
- Osteoporosis (long-term use)
What is the difference b/w type I and type II HIT?
Type 1 is not immune-mediated and occurs within 1st 48h of heparin use and results in mild decrease in PLT.
Type 2 is immune-mediated and occurs 5-14d after heparin use
What are the 3 risk factors associated with HIT in heparin pts?
- Heparin for 4 days
- Female sex
- Recent surgery
What is 1 of the procoagulants that is produced during HIT?
Thrombin (Factor IIa)
What is the most common diagnostic tool for HIT?
Solid-phase enzyme immunoassays (EIA) to detect HIT antibodies
When a pt is diagnosed with HIT, which is the best for pt after d/c heparin?
or transfuse platelets?
Neither. Both may potentiate procoagulant state
What is the duration of tx for HIT with DTI's?
Minimum of 30 days. If thrombosis occurs, tx with anticoagulant for minimum of 6
When would one initiate warfarin in pt resolved with HIT?
After PLT>100,000/mm3, may initiate 5 days before alternate anticoagulant is d/ced
For enoxaparin, what is the DVT prophy dose for hip, knee replacement? For abdominal surgery?
When to initiate?
Hip: 30mg sc q12h 12-24hr post-op or 40mg sc daily 9-15hr pre-op for at least 10 days up to 35 days
knee: 30mg sc q12h. Start 12-24h post-op for 7-10 days, up to 35 days
Abd surgery: 40mg sc daily. Start 2hrs pre-op, for NMT 12 days
Both: CrCL<30: 30mg sc daily
What is DVT/PE tx dose with enoxaparin? Renal dosing?
1mg/kg sc BID, or 1.5mg/kg daily
CrCL<30: 1mg/kg sc daily
What is dosing of enoxaparin for MI, unstable angina, thrombolytic adjunct, and PCI? Renal dosing? Age >75?
- 1mg/kg sc q12h with ASA
- Age>75: 0.75mg/kg sc q12h
- CrCL<30: 1mg/kg sc daily
What kind of allergy should one be cognizant about for heparin and LMWH?
What are the dosage forms of enoxaparin?
30/0.3ml, 40, 60, 80, 100mg/ml, 120mg/0.8ml, 150mg/ml pre-filled syringes
What are the dosage forms of fondaparinux?
2,5, 5, 7.5, 10mg pre-filled syringes
What is the BBW for enoxaparin? For fondaparinux? For desirudin?
Pt receiving anesthesia (epidural, spinal) or undergoing spinal puncture are at risk for hematomas and subsequent paralysis
What is DVT prophy dose for fondaparinux and duration? When do u initiate? Any restrictions?
- 2.5mg sc daily 6-8hrs post-op for 10 days, up to 35 days
- CI in adults <50kg
What is renal dose-adjustment for fondaparinux for DVT prophy n tx?
CrCL<30: Use is CI
What is dose of fondaparinux for VTE tx and duration?
- Wt<50kg: 5mg sc daily
- 50-100kg: 7.5mg sc daily
- >100kg: 10mg sc daily
- for 5-9 days up to 26 days
What are the brand names for DTI's - argatroban, lepirudin, and bivalirudin?
- Argatroban (Novastan)
- Lepirudin (Refludan)
- Bivalirudin (Angiomax)
When do you start renally dose-adjusting for argatroban, lepirudin, bivalirudin, and desirudin?
- Argatroban: No renal d-adj req'd
- Lepirudin: CrCL<60
- Bivalirudin: CrCL<30
- Desirudin: CrCL<60
What is the only indication for desirudin (Ipravask) and dosing?
VTE prophy for hip replacement: 15mg sc q12h
What are the dosage forms of dabigatran? How long is it good for after opening? Storage instructions? How long are blister packs good for?
- 75, 150mg caps
- Use within 4 months, keep in original container and protect from moisture
Blister packs: Good until exp date (~6-12 mons)
What are the renal dose-adjustments for dabigatran? What is indication and dosing?
- Non-valvular A-fib: 150mg po BID
- CrCL<30: 75mg po BID
- CrCL<15: DO NOT USE
When do you initiate warfarin with dabigatran based on CrCL?
- CrCL>50: Initiate warfarin 3 days before d/c dabigatran
- CrCL 31-50: Initiate warfarin 2 days b4 d/c dabigatran
- CrCL 15-30: Initiate warfarin 1 day before d/c dabigatran
- CrCL<15: No recommendation
Besides bleeding, what other common s/e occurs with dabigatran? And why does this occur?
Dyspepsia, abd discomfort
Better absorbed at lower pH, so caps have an acidic core that can cause GI irritation
Compared to warfarin, how many more strokes are prevented in Afib pts with dabigatran?
5 more strokes prevented per 1000 pts/yr
What is the BBW for rivaroxaban?
Pt receiving neuraxial anesthesia (epidural, spinal) or undergoing spinal puncture are at risk for hematomas and subsequent paralysis.
D/C of drug in pt w/non-valv Afib can put pt at inc'd risk of thrombosis (i.e. stroke)
What are the 3 indications for rivaroxaban?
- Non-valv Afib
- Prophy for DVT in hip/knee surgery
- Tx of DVT/PE
What are the dosage forms of rivaroxaban? What is its metabolism?
- 10, 15, 20mg oral tabs
- Major 3A4 substrate
What is dosing of rivaroxaban for non-valv Afib? Renal d-adj?
- CrCL>50: 20mg po daily with dinner
- CrCL 15-50: 15mg po daily with dinner
- CrCL<15: Avoid use
What is dosing for rivaroxaban for DVT prophy after hip/knee surgery? Renal d-adj? Duration?
10mg po daily w/o regard to meals, for 35 days (hip), or 12 days (knee)
Do not use in CrCL<30
What is dosing of rivaroxaban in VTE tx? Renal d-adj?
- 15mg po bid wf x21d, then 20mg po daily wf
- CrCL<30: Do not use
What is the BBW for warfarin? And what are 3 side efx to watch out for?
May cause major or fatal bleeding
Bleeding, skin necrosis, purple toe syndrome
How is warfarin metabolized (substrate, etc)?
- Major CYP2C9 substrate
- Minor 1A2, 2C19, and 3a4 substrate
- Weak 2C9/19 inhibitor
What are some CYP inducers (7) that could decrease INR with warfarin?
What are some 2C9 inhibitors that might increase INR with warfarin? (8)
- Azole antifungals
- Macrolide Abx
Which 2 herbs/supplements may reduce effectiveness of warfarin (may dec INR)?
For warfarin pt that is bleeding and needs vitamin K, what are the 2 preferred routes (and which is preferredover the other?)?
- IV causes anaphylaxis in 3/100,000 pt so infuse slowly
- SC -- variable response
- IM - hematoma formation risk
What 3 minor surgeries does not warrant warfarin temp d/c?
- Minor dental
- Cataract surgery
What is anticoag recommendation for pt with Afib>48hrs or unknown duration, who will be recieving cardioversion in the future?
Anticoagulate for at least 3 weeks prior to and 4 weeks after cardioversion when NSR is restored
What is anticoag recommendation for pt in Afib<48hr undergoing elective cardioversion?
Start full therapeutic anticoag at presentation and continue for at least 4 weeks after cardioversion while pt is in NSR
What are the half-lives of the Vit-K--dep factors blocked by warfarin?
- II: 60hrs
- VII: 6hrs
- IX: 24hrs
- X: 40 hrs
Per ACCP, what are Vit K recommendations for warfarin users when:
1. INR >10 w/o bleed
2. INR any value with major bleed
Check ACCP and update
When do you convert warfarin to dabigatran? When can one see true INR value after dabigtran is converted to warfarin?
Warfarin to Dabigatran when INR<2.0
After d/c dabigatran for 2 full days, will see INR effects from warfarin (since Pradaxa affects INR)