Anticoagulation

Question 1

Unfractionated Heparin

Answer 1

Anticoagulation
• Naturally present in body (mast cells, basophils)
• Average Elimination Half-life: 1.5 hrs
• Time to steady state with a constant IV infusion = 6 hrs (4 half lives)
MOA
- Inactivates IXa, Xa, XIa, XIIa + Thrombin
• Heparin (UFH) binds to antithrombin and speeds up these reactions
LAB MONITORING
• Activated partial thromboplastin time: aPTT or PTT
• Anti-Factor Xa levels
• check patient platelet counts during heparin therapy (same with LMWH)
C/I (not really?)
• Pregnancy Category B = Safe to Use
• *If HIT occurs or has occurred previously in a patient, an IV direct thrombin inhibitor, such as argatroban, is indicated. For sure, do NOT use heparin or a LMWH!

Question 2

Low Molecular Weight Heparin

Answer 2

Anticoagulation
MOA
- Binds to antithrombin to speed up activity of inactivation of Xa (primarily) some IIa.
- Can’t really bind to thrombin (IIa) because it’s not long enough.
• LMWHs inactivate Xa but have less effect on thrombin (some molecules not long enough)
LAB MONITORING
– Do not prolong PTT unless dose high
• Usually no lab monitoring required
• For certain patient p Populations (obesity, renal failure) can use Anti-Factor Xa levels
• PTT not used
BETTER THAN HEPARIN
– Easier to administer: subcutaneous, 1-2 x/day dosing
– Dosage and anticoagulant effect easier to predict; dose based on body weight = can be used by patients.
– Lab monitoring not necessary in all patients
– Need dose adjustment in renal disease
– Less chance of inducing immune-mediated thrombocytopenia
C/I
- Pregnancy Category B = Safe to Use
- *If HIT occurs or has occurred previously in a patient, an IV direct thrombin inhibitor, such as argatroban, is indicated. For sure, do NOT use heparin or a LMWH!

Question 3

Heparin Induced thrombocytopenia

Answer 3

Anticoagulation
*Main Adverse Effect of Heparin and LMWH
2 TYPES OF HIT
- One is a benign, early-onset version.
- The later-onset, potentially fatal type is the auto-immune reaction to the PF4-Heparin complex. Death is usually from thrombosis.
- Remember to check patient platelet counts during heparin therapy.

Question 4

Fondaparinux

Answer 4

Anticoagulation
Indirect Xa Inhibitor
- *Alternative to HIT/Heparin Allergy 
- Very low to rare incidence of thrombocytopenia
MOA
- The drug is the unique pentasaccharide sequence that UFH and LMWH use to bind to AT. Only Xa reactions. 
LAB MONITORING
• Usually no lab monitoring required
• For certain patient populations (obesity, renal failure) can use Anti-Factor Xa levels
• PTT not used
C/I
- Pregnancy Category B = Safe to Use

Question 5

Protamine

Answer 5

Anticoagulation
MOA/Therapeutic Use
- *Heparin/LMWH Reversal
- When administered alone, protamine has an anticoagulant effect.
- However, when it is given in the presence of heparin (which is strongly acidic), a stable salt is formed which results in the loss of anticoagulant activity of both drugs.
- Neutralization of heparin occurs within five minutes after intravenous administration.
*Note: BEST ADJUSTMENT = TINCTURE OF TIME: Decrease dose to stop because half life is quite short.

Question 6

Bivalirudin, Argatroban

Answer 6

Anticoagulation
Direct Thrombin Inhibitor
MOA
- Direct Thrombin Inhibitor
• Hirudin: anticoagulant from leech saliva
• Cardiac cath-lab use (IV); *alternative anticoagulant when heparin allergy or HIT