CASE 4 A 60-year-old male presents at the ER with acute onset shortness of breath.

This is associated
with increasing lower extremity edema on the left side. There was no history of trauma, long travel,
infection nor any other immediate precipitating event. Electrocardiogram was consistent with a finding of
new onset atrial fibrillation. Ultra sonogram Doppler study of the lower extremities revealed occlusive left
side deep venous thrombosis of the popliteal vein. A CT angiography demonstrated segmental and sub-
segmental pulmonary emboli of the right lower lobe with no evident pulmonary edema. He is started on
heparin which was eventually bridged to warfarin. He is also given digoxin for the atrial fibrillation.

1. Differentiate heparin and warfarin based on:

Heparin Warfarin
Route of administration IV or subQ PO
Site of action Antithrombin Vitamin K epoxide reductase
And onset of action Rapid (minutes) Slow (hours)
Mechanism of action Activates antithrombin, which Inhibit synthesis of vitamin K
then inactivates thrombin and dependent clotting factors,
factor Xa including prothrombin and
factor X
Duration of action Brief (hours) Prolonged (days)
Treatment of acute overdose Protamine sulfate Vitamin K
Monitoring aPTT PT
Ability to cross placenta No Yes

2. Differentiate UFH from LMWH.

UFH LMWH
Molecular weight 5000-30000 <9000
Bioavailability Low High
Clotting factors affected IIa(thrombin), IXa, Xa Xa (less effect on thrombin)
Dosing Loading followed by continuous OD or BD
infusion
Monitoring aPTT None

3. What blood dyscrasia is associated with heparin? Describe the adverse reaction.

In HIT, the immune system forms antibodies against heparin when it is bound to a protein called
platelet factor 4 (PF4). These antibodies are usually of the IgG class and their development usually takes
about five days. The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of
the antibody then binds to the FcIIa receptor, a protein on the surface of the platelet. This results in
platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots;
the platelet count falls as a result, leading to thrombocytopenia.

4. What drug interactions are commonly associated with warfarin?

Warfarin plus acetaminophen Increased bleeding, INR

Warfarin plus acetylsalicylic acid, NSAIDs Increased bleeding, INR
Warfarin plus ciprofloxacin, clarithromycin, Increased effect of warfarin
erythromycin, metronidazole