Review Question - QID 107401

The patient in this scenario has developed a deep vein thrombus (DVT). The next best step is to start a heparin drip and monitor the activated partial thromboplastin time (aPTT) until therapeutic levels are reached.

DVT may be provoked by immobility and should be suspected in cases of asymmetrical extremity swelling. Once diagnosed, anticoagulation should be initiated to prevent further growth of the thrombus and pulmonary embolism. Unfractionated heparin is a cofactor for antithrombin, which inactivates coagulation factors II, X, IX, XI, XII thereby, increasing aPTT time.

Wigle et al. review that heparin dosing should be titrated such that the aPTT is 1.5 to 2.3 times the normal control, approximately 46-70 seconds. Next, the patient will likely need to be transitioned from heparin to oral anticoagulation therapy, typically with warfarin. Warfarin decreases the synthesis of vitamin K dependent clotting factors II, VII, IX, X, C and S.

Kearon et al. recommend that length of time for treatment of provoked DVTs (such as post-surgery) should be three months. The choice of anticoagulation treatment is based upon the patient's risk factors such as bleeding or falls. Patients that take warfarin will require frequent monitoring to ensure that patients are at therapeutic levels.

Illustration A demonstrates the classical coagulation cascade including the targets of unfractionated heparin (UFH), low molecular weight heparin (LMWH) which predominantly inhibits factor Xa and warfarin. Note that warfarin also inhibits factors C and S (not shown).

Incorrect Answers:
Answer 1: Heparin also blocks factor X, which is common to both the intrinsic and extrinsic coagulation cascade pathway, and prothrombin time may also increase. However, heparin blocks more coagulation factors in the intrinsic pathway and thus, aPTT increases first and by much more.
Answer 3: The internationalized normal ratio (INR) is monitored in patients who are taking warfarin. Warfarin levels are therapeutic when the INR is elevated, typically around 2-3.
Answer 4 & 5: Heparin itself does not cause changes in creatinine or liver transaminases. However, it is important to note that low molecular weight heparin such as enoxaparin is renally cleared and should be avoided in patients with chronic kidney disease as the risk of bleeding may increase.