Anticoagulants and Thrombolytics Flashcards
What monitoring tool is used to assess function of Unfractionated Heparin?
PTT = Partial Thromboplastin Time
- INTRINSIC pathway
How does Unfractionated Heparin work?
binds Antithrombin III –> which IRREVERSIBLY inhibits Thrombin (Factor II) and Factor Xa
What is the difference in administration of Unfractionated Heparin for acute vs prophylactic treatment?
Acute? = Intravenous
PPx? = Subcutaneous (q10-12 hr)
What is HIT?
Heparin-induced Thrombocytopenia
- immune system generates antibodies against heparin-platelet factor 4
- paradoxical thrombosis in the setting of thrombocytopenia
What are 3 major adverse effects of Unfractionated Heparin use?
- Heparin-induced Thrombocytopenia (HIT)
- Osteoporosis
- HYPOaldosteronism (HYPERkalemia –> RTA Type 4)
What is the reversal agent of Unfractionated Heparin and how does it work?
Protamine Sulfate
- positive charge binds to the negative charge of heparin, inactivating it
How does Low Molecular Weight Heparin (LMWH) work?
binds to Antithrombin III –> inhibits Factor Xa but has LESS EFFECT on Thrombin (Factor II)
Is Low Molecular Weight Heparin longer-acting or shorter-acting?
What medical condition effects the half-life of LMWH?
longer-acting = has prolonged half-life
RENAL INSUFFICIENCY increases the 1/2 life of LMWH
How is Unfractionated Heparin cleared vs LMWH?
Unfractionated Heparin? = processed by LIVER
LMWH? = processed by KIDNEYS
Which anticoagulant would be better for a patient with liver disease?
LMWH
Which anticoagulant would be better for a patient with kidney disease?
Unfractionated Heparin
Are heparin products safe for pregnancy?
YES!! –> LMWH better than Unfractionated Heparin though
- easier to monitor, less side effects, more predictable
How does Fondaparinux work?
binds to Antithrombin III –> inhibits Xa more than Thrombin (Factor II)
- binds with more specificity than LMWH
What are the 3 heparin-based medications used for anticoagulation?
Rank them in order of descending size.
Unfractionated Heparin, LMWH, Fondaparinux
heparin > LMWH > Fondaparinux
Which heparin product has the LOWEST risk of HIT?
Fondaparinux
What are the 3 main Direct Thrombin Inhibitors and when are they classically used?
Bivalirudin, Argatroban, Dabigatran
- used in the setting of HIT (switch from heparin)
What are the 2 main Direct Factor Xa Inhibitors and in what situation are they used for?
Rivaroxaban, Apixaban
- used as ORAL MEDICATION = good for long-term prophylaxis because they do not have to be monitored
What condition are Factor Xa Inhibitors typically used for?
Prophylaxis of Atrial Fibrillation
What proteins are responsible for resolution of clots?
Protein C and Protein S
What factors and proteins of the coagulation cascade require Vitamin K to function?
Factors 10, 9 ,7, 2 and Protein C/S
What does Warfarin work?
inhibits VKOR (Vitamin K epOxide Reductase) = prevents conversion of Vitamin K epoxide (inactive) to Vitamin K (active)
- prevents activation of Factors 10, 9, 7, 2 and Proteins C/S
How is Warfarin administered and how long does it take for onset of effects?
Administration = ORAL
Onset of effects = 8-10 hours
What is the half-life of Warfarin and what is the usual dosing per day?
1/2 life = 36-42 hours
- typically QD dosing
What is used to monitor Warfarin and what is the normal range for this value?
Use PT/INR (International Normalized Ratio)
Normal INR = 2-3
Is Warfarin a good choice for pregnant patients?
NO! –> crosses the placenta
- can lead to in-utero hemorrhages/abnormal bone growth
What is the “heparin bridge”?
When starting Warfarin, heparin is co-administered, as Warfarin effects Protein C/S quicker than Factors 10, 9, 7, 2 and can lead to skin necrosis from paradoxical thrombosis
- heparin blocks thrombosis from occurring due to decreased levels of Protein C/S from early Warfarin effects
- without heparin co-administration, patients can develop serious SKIN NECROSIS
What two options are available for Warfarin reversal?
Exogenous Vitamin K = delayed effects
Fresh Frozen Plasma = immediate effects (has formed coagulation factors)