Hematology: Anticoagulants

Indirect-Acting Anticoagulants

Unfractionated Heparin (UFH/Heparin)

Mechanism: Activates Antithrombin (AT-III)
- Indirectly Inhibits Factors Xa & IIa
Monitor: PTT
Reversal: Protamine Sulfate
- Give Slowly to Prevent Hypotension & Bradycardia
- Originally Made from Salmon Sperm
Hold Timing Prior to Surgery: 6-12 Hours
- Half-Life: 45-60 Minutes
Complications:
- Bleeding
- Heparin-Induced Thrombocytopenia
  - *See Hematology & Oncology: Heparin-Induced Thrombocytopenia (HIT)
  - Check Platelet Count Every 2-3 Days
- Osteoporosis
- Skin Necrosis

Low Molecular Weight Heparin (LMWH)

Includes:
- Enoxaparin (Lovenox)
- Dalteparin (Fragmin)
Mechanism: Activates Antithrombin (AT-III)
- Indirectly Inhibits Factor Xa (Minimal Effect on Factor IIa)
- Half Life Over Double Heparin
Monitor: Usually None
- Can Use a Factor-Xa Assay If Needed (Therapeutic Ranges Poorly Established)
Reversal: Protamine Sulfate (Only Partial Neutralization – 60%)
Hold Timing Prior to Surgery: 12-24 Hours
- Half-Life: 3-7 Hours
Avoid in Renal Disease (AKI/CKD)
- May Cause Reduced Clearance
- Increased Risk of Major Hemorrhage
Complications:
- Bleeding
- Heparin-Induced Thrombocytopenia
  - *See Hematology & Oncology: Heparin-Induced Thrombocytopenia (HIT)
  - Lower Risk Than UFH But Still at Risk
- Skin Necrosis

Comparison of UFH to LMWH

UFH Benefits:
- Easier to Titrate & Discontinue – Rapid Onset & Short Half-Life
- Can Monitor Using PTT
- Safe to Use in Renal Failure
- Easier to Reverse
LMWH Benefits:
- Greater Bioavailability
- Better Correlation of Dose to Response
- Lower Risk of Bleeding & HIT
- Lower Risk of Osteoporosis
- Longer Duration of Action Requires Less Frequent Administration

Fondaparinux (Arixtra)

Mechanism: Activates Antithrombin (AT-III)
- Indirectly Inhibits Factor Xa (No Effect on Factor IIa)
Monitor: Usually None
- Can Use a Factor-Xa Assay If Needed (Therapeutic Ranges Poorly Established)
Reversal: None
Hold Timing Prior to Surgery: 36-48 Hours
- Half-Life: 17-21 Hours
- Very Long & Generally Not Used in the ICU
Avoid in Renal Disease (AKI/CKD)
- May Cause Reduced Clearance
- Increased Risk of Major Hemorrhage
Complications:
- Bleeding
- *No Risk of HIT

Drugs

Warfarin (Coumadin)

Mechanism: Inhibits Vitamin K-Dependent Decarboxylation of Glutamic Residues of Clotting Factors
Inhibits: Factor II, VII, IX, X, Protein C & S
- *See Hematology & Oncology: Coagulation Cascade
Monitor: INR
Reversal:
- Fastest: 4-Factor PCC (Immediate – No Thaw Time)
- FFP (Immediate – Must Be Thawed First)
- Vitamin K (6-12 Hours)
  - Permanent – FFP & PCC are Temporary
Hold Timing Prior to Surgery: 5 Days
- Half-Life: 36-42 Hours
- May Consider Bridging with Short-Acting Anticoagulation
Complications:
- Bleeding
- Skin Necrosis
  - Due to Relatively Short Half-Life of Protein C & S (Initially Hypercoagulable)
    - Higher Risk with Protein C Deficiency
  - Prevent by Co-Administration of Heparin While Initiating
  - Management: Stop Coumadin, Give Vitamin K & Therapeutic Heparin
- Not Safe in Pregnancy (Crosses Placenta)
  - OK to Use While Breastfeeding

Direct Thrombin Inhibitors (DTI)

Drugs:
- Univalent Drugs:
  - Argatroban
  - Dabigatran (Pradaxa)
- Bivalent Drugs:
  - Bivalirudin (Angiomax) – Analog of Hirudin
    - Hirudin – Occur Naturally in Leeches
  - Lepirudin – Discontinued
Mechanism: Directly Inhibits Factor IIa (Thrombin)
Metabolism:
- Argatroban: Liver Mn
- Others: Kidney
Monitor: Usually None
- Can Prolong PT & PTT (Unreliable)
Reversal:
- Dabigatran: Idarucizumab (Praxbind) or Dialysis
- Others: None
Hold Timing Prior to Surgery: 2-3 Days
- Half-Life:
  - Dabigatran (Pradaxa): 12-17 Hours
  - Others: 30-60 Minutes

Direct Factor Xa Inhibitors

Excretion of Direct Thrombin Inhibitors

Direct Factor Xa Inhibitors