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What are the three classes of drugs that inhibit coagulation?
Anticoagulants

Fibrinolytics

Anti-platelet drugs
What kind of drug are heparins?
Anticoagulants
How are heparins administered to patients?
IV

Subcutaneous
What is the main mechanism of heparins?
1. Potentiates antithrombin / serine protease (thrombin, F IXa, F Xa, F XIa) complexes

2. Irreversibly binds and inactivates factors

3. Also binds and inhibits platelets
What serine proteases are especially inactivated by unfractionated heparin?
Thrombin

F Xa
What are the clinical uses of unfractionated heparin?
Prevent venous thromboembolism

Cardiac bypass surgery
What are the limitations of unfractionated heparin and what must be done to deal with these limitations?
Narrow therapeutic window
- Monitor PTT carefully

Binds plasma proteins, endothelial cells, platelets
- Variable dosing

Monitor platelet counts regularly
What are complications associated with unfractionated heparin?
Bleeding

Heparin-induced thrombocytopenia (HIT)
What is the hematological problem seen in heparin-induced thrombocytopenia?
Thrombocytopenia (low platelets)

Thrombosis
What causes thrombocytopenia and thrombosis in heparin-induced thrombocytopenia?
IgG antibodies made against the heparin + platelet factor 4 complex causing:
- Platelet aggregation
- Platelet activation
How is heparin-induced thrombocytopenia diagnosed?
Decreased platelet count

HIT assay:
- Presence of antibodies against heparin + platelet factor 4 complex
How is heparin-induced thrombocytopenia treated?
Discontinue heparin

Start thrombin inhibitor anticoagulant
Which clotting factors does low molecular weight heparin (LMWH) especially inactivate?
F Xa > thrombin
What are the benefits of low molecular weight heparin (LMWH) over unfractioned heparin (UFH)?
Less platelet interaction

More predictable bioavailability and dosing

Longer half life

Do not need to monitor as much
How is low molecular weight heparin (LMWH) administered?
Subcutaneously
What are the limitations of low molecular weight heparin (LMWH)?
Not for patients with renal failure

No antidote
What are the side effects of low molecular weight heparin (LMWH)?
Bleeding

Bruising at injection site
What patients are prescribed direct thrombin inhibitors?
Patients with heparin-induced thrombocytopenia
How are direct thrombin inhibitors administered?
IV
How are direct thrombin inhibitors monitored?
PTT
What patients are prescribed oral direct thrombin inhibitors?
Patients with atrial fibrillation
What conditions are oral direct thrombin inhibitors meant to prevent?
Stroke
What are the benefits of oral direct thrombin inhibitors?
No monitoring

Fixed dose
What is the mechanism of Warfarin / Coumadin?
Inhibit reductase that recharges vitamin K
- Prevents activation of vitamin K-dependent factors (F II, F VII, F IX, F X)
How long does Warfarin / Coumadin take to have effect?
3-5 days
What conditions are Warfarin / Coumadin used to treat?
Deep venous thrombosis

Arterial thrombosis
How is Warfarin / Coumadin administered?
Orally
What are the limitations of Warfarin / Coumadin?
Multiple drug and food interactions

Narrow therapeutic window
- Metabolized by liver P450

Crosses placenta
- Causes birth defects
How is Warfarin / Coumadin monitored?
INR for PT
What are side effects of Warfarin / Coumadin?
Bleeding

Skin necrosis
What is the antidote for Warfarin / Coumadin overdose and what must be done in addition to this?
Vitamin K
- Takes time to work

Must give with FFP
What type of inhibitor of coagulation is tissue plasminogen activator (tPA)?
Fibrinolytic agent
How does tissue plasminogen activator (tPA) lyse clots?
Converts plasminogen to plasmin which effectively degrades fibrin clots
In what events is tissue plasminogen activator (tPA) used?
Clots in:
- Acute MI
- Stroke
- Large PE
How is tissue plasminogen activator (tPA) administered?
IV
What are contraindications for tissue plasminogen activator (tPA) use?
GI bleeding

Neurosurgery

Head injury
What are the anti-platelet agents used?
Aspirin / Ibuprofen / Motrin

Dipyridamole

Clopidogrel

GPIIb / IIIa inhibitors

PAR I inhibitors
What are side effects of anti-platelet agents?
Mucosal bleeding

GI bleeding
What is the treatment protocol for venous clots (DVT / PE)?
1. Start anticoagulants immediately:
- Low molecular weight heparin with Warfarin

2. Check INR:
- If >2 for two days, stop low molecular weight heparin and continue Warfarin

3. Continue Warfarin for 3-6 months and monitor with INR
What are some non-pharmaceutical treatments for deep venous thrombosis?
Compression stockings

Inferior vena cava filter
When are inferior vena cava filteres used?
Patients with lower extremity deep venous thrombosis who cannot be on anticoagulants
What is the common prophylactic treatment for venous clots?
Low molecular weight heparin
or
Unfractionated heparin
What patients recieve prophylactic treatment to prevent venous clots?
All patients undergoing surgery

Patients under continuous bed-rest

History of deep venous thrombosis
What agents are used to treat arterial thromboses?
Tissue plasminogen activator (tPA)
- Only agent that gets rid of clot

Heparins

Warfarin

Anti-platelet agents
- For prevention