Anticoagulants Junk Flashcards
What clotting factors are found within the Extrinsic Pathway?
VII, TF, X
What clotting factors are found within the Intrinsic Pathway?
XI, IX, VIII, X
What clotting factors are found with in the Common Pathway?
V, X, Thrombin (II), Fibrin (I), XIII
What is the MOA for Warfarin?
To inhibit the Vitamin K Reductase
- Causing a DECREASE in clotting factors.
What is the CYP what activates Warfarin?
CYP2C9
How long does it take before you may start seeing the effects of Warfarin?
About 3-5 Days; because it takes time to deplete all of the clotting factors from Reduced Vit K
- II: 60-100 Hours; VII: 4-6 Hours; IX: 20-30 Hours; X: 24-40 Hours
What is the initial dose of Warfarin?
5mg once daily
- Should overlap with a UFH/LMWH/Xa for 5 day AND until INR is normal
How to reverse a Warfarin Overdose?
-Can give high amounts of Vit K, which will reverse the inhibition of Vit K Reductase. Allowing for the clotting factors to be made again
-PCC [contains II, VII, IX, X, Protein C & S]
How do the genetic difference affect CYP2C9?
- 1*: normal wild type
- 2*: decrease clearance by 40-70%
- 3*: decrease clearance by 90%
-1/2: 20% dose reduction
-2/3 & 1/3: 35% dose reduction
-3/3: 80% dose reduction
How do the genetic difference affect VKORC1?
- A: Lower Dose; Higher Sensitivity
- G: High Dose; Lower Sensitivity
What is the cause of Warfarin Necrosis?
The initial dose of Warfarin will cause Protein C & S to become lower than the rest of the clotting factors [II, VII, IX, X] and also leaving factors V & VIII active as well = hypercoagulable
- can take with heparin to help with this
What is INR?
INR: the total time it take for the blood to clot
What drugs can increase INR?
Metronidazole, Amirodene, Cipro, Fluoxitine, Bactrim
- Will make it to where the blood clots slower
What drugs can decrease INR?
Rifampin
- Will make it to where the blood clots higher
What are the contraindications for Warfarin?
- Pregnancy: has the ability to pass through the plaecenta.
- Liver Disease: a lot of the clotting factors are made within the liver so if the liver is not making any of the clotting factors and warfarin decreases them even more = Warfarin will cause an INCREASED bleeding.
What is the MOA for heparin [UFH]?
It is going to bind to Anti-Thrombin, causing it to accelerate the action of it. This will cause inhibition of BOTH Thrombin and Xa; a long chain with a pentasaccharide binds to AT and wraps around and inhibits Thrombin or Xa.
What is the aPTT?
A test that determines how fast it takes for the blood to clot without TF
What are the adverse affects with UFH?
Iatrogenic Hemorrhage: hemorrhage at any site of injection
- >50 years old, HTN, Ulcers, Antiplatelet Drugs
HIT
Osteoporosis
What is HIT?
HIT - Thormbocytopenia: A decrease in the number of platelets
What is the mechanism of HIT?
Heparin will bind to the PF4 receptor on the platelet:
- Heparin + PF4 on the platelet will cause the antibody IgG to become activated. IgG will bind to Heparin + PF4 marking it for death. This is know as Type 2 [Immunogenic]; for first time users of Herparin, this may occur in 30 days while second time users may experience this within 1 day
-Heparin + PF4 on the platelet will cause the platelet to become activated, initiating the clotting cascade, causing an overall decrease in platelets
How to you reverse Heparin?
Protamine Sulfate: this will directly bind to the Heparin molecule causing inactivation.
- Doesn’t really affect the LMWH [Enoxiparin and Daltaparin]
- HAS NOT EFFECT AT ALL on fondaparinux
What is the MOA for Low Molecular Weight Heparins [LMWH]?
The MOA for the LMWH is pretty much the same as the MOA for UFH, but since this has a low molecular weight it the pentasaccharide chain is much shorter, ONLY inhibiting Xa.
What is the dosing for LMWH?
Enoxiparin:
-Prevention: 30mg BID (surgery) & 40mg daily (medical?)
-Treatment: 1mg SQ BID or 1.5mg SQ Daily
-Renal dysfunction: 30mg BID (prevent) & 1mg SQ Daily (medical)
Which ones work better within the Liver? UFH or LMWH?
UFH; LMWH do not!!
Does LMWG cause HIT or Osteoporosis?
Can still cause it, but is very less likely to develop HIT
What is the MOA for Fondaparinux?
It is the same MOA as UFN and LWMH, but this one is ONLY the pentasaccharides and will ONLY inihbit the Xa\
What is the main preventions of Fondaparinux?
THA, TKA, Hip replacement, Abdominal surgery
What are some of the dosing options of Fonadparinux?
Treatment: 2.5mg daily
Prevention: It is based on the patients weight;
- <50kg: 5mg
- 7.5-10kg: 50 - 100mg
- 10kg: 10mg
What is the MOA for the Direct Factor Xa Inhibitiors?
They directly bind to factor Xa; stoping the activity of the common pathway.
- will affect multiple thrombin and fibrin
What is the reversal medication for Direct Factor Xa Inhibitors?
Andexant Alfa: it will bind directly to the Direct Factor Xa Inhibitor - inhibiting them
What are Direct Factor Xa Inhibitors used for?
Postoperative Prevention, DVT/PE Treatment, Secondary Prevention, Non-AFIB, VTE Prevention
Postoperative Prevention dosing for Xa?
Rivaroxaban: 10mg DAILY for 12 days (hip) and 35 days (knee) [avoid: CrCl < 30]
Apixaban: 2.5mg BID for 12 days (hip) and 35 days (knee)
Non-AFIB dosing for Xa?
Rivaroxaban: 20mg DAILY [15-50 CrCl = 15mg]
Apixaban: 5mg BID
-CONSIDERATION: >80 years old, <60kg, Scr >1.5 = 2.5mg
Edoxaban: 60mg DAILY [15-50 CrCl = 30mg]
DVT/PE Treatment dosing for Xa?
Rivaroxaban: 15mg BID for 3 weeks, then 20mg DAILY
Apixaban: 10mg BID for 7 days, followed by 5mg BID
Edoxaban: 60mg DAILY
-CONSIDERATIONS: <60kg = 30mg DAILY & 5-10 parental anticoag [UFH or LMWH]
Secondary Prevention dosing for Xa?
Rivaroxaban: 20mg PO DAILY
Apixaban: 2.5mg PO BID
-CONSIDERATION: after 6 months of initial therapy.
VTE Treatment dosing for Xa?
Rivaroxaban: 10mg PO DAILY [avoid: CrCl < 30]
Betrixaban: 160mg PO (1DAY) then 80mg PO DAILY [ONLY INDICATION]
What is the mechanism for Direct Thrombin Inhibitors?
Directly binds to Thrombin; inhibiting the formation of Fibrin = not making the crosslinked fibrin mesh.
Are Direct Factor Xa Inhibitors used in patients that have a prosthetic heart valve?
No, its contraindicated
What type of thrombin does Heparin affect? Direct Thrombin Inhibitors?
-Heparin ONLY affects soluble thrombin
-DTIs can affect BOTH soluble and fibrin-bound thrombin
What are the DTI?
Argatroban (IV), Dabigitran (IV), Bivalirudin (PO)
Which one of the DTIs are approved for treatment and/or prevention of HIT?
Argatroban
-Dabiiatran & BIvalirudin can also be used too?
What medication can reverse the action of the DTIs?
Idariczumab: Monoclonal Antibody that bind directly to Dabigitran
-DOES NOT BIND TO THE OTHER DTIs
What medication can be used in Valvular AFIB?
ONLY Warfarin: because of the slow onset
What does Bivalirudin?
IV form of DTI
-0.7mg/kg then 1.75mg/kg/h
-Can be used in HIT & UFH alternative during PCI
What does Argatroban?
IV form of DTI
-2mcg/kg/min
-Can be used in HIT & overlap with Warfarin until INR is >4?
Postoperative Prevention dosing for Thrombin Inhibitors?
Dabigitran: Day of surgery use 110mg DAILY; NOT the day of surgery use 220mg DAILY; maintenance use 220mg DAILY
ONLY FOR HIP REPLACEMENT
Non-Valvular AFIB dosing for Thrombin Inhibitors?
Dabigitran: 150mg BID [CrCl 15-50: 75mg BID]
DVT/PE Treatment dosing for Thrombin Inhibitors?
Dabigitran: 150mg BID
-needs a 5-10 parental anticoag [UFH or LMWH]
What is VIRCHOW’s Triad?
Its what can cause a thrombosis
-Hypercoag, statsis, endothelial damage
-give warfarin?
What are the five D’s associated with warfarin?
Drugs, Drinking, Diseases, Diet, Doses
-Bleeding and Bruises
What causes the increase in HDL within Niacin?
Apo-A
What is CHA2DS2-VASc Score?
C-CHF (1)
H-HTN (1)
A-Age > 75 (2)
D- DM (1)
S- Stroke (2)
V- Vascular Disease (1)
A - Age 65-74 (1)
C- Famale (1)
What is HAS-BLED score?
H- HTN (1)
A- Liver and renal function (1-2)
S- Stroke (1)
B- Bleeding (1)
L- INR (1)
E- Age >65 (1)
D- Drugs (1-2)
