Coagulation treatments

Ok, so now we know about a few conditions and abnormalities, let’s review a few common anticoagulant drugs.

Heparin:
Remember antithrombin from the fibrinolytic rundown? Heparin activates antithrombin which then inactivates thrombin, factors 10a, 9a, 11a, and 12a. Heparin is a powerful anticoagulant. Heparin is also naturally made in the body in small quantities and has many functions. Heparin therapy is monitored by the APTT test.

Nerdy Note
Heparin is a notoriously difficult molecule to synthesize. Synthetic heparin is yet to be created and for that reason all of the heparin used in the United States comes from pig intestines. Most of the heparin comes from China due to their high consumption of pigs. Heparin is present in other animal tissues however the only approved form in the United States is from pig intestines. There was a great piece written in Chemical and Engineering News in October 2016 which takes a deep dive into the heparin industry which can be fraudulent at times. http://cen.acs.org/articles/94/i40/Making-heparin-safe.html

Heparin induced thrombocytopenia and thrombosis:
Patients who are new to heparin therapy should have their platelet count monitored frequently because some patients will make antibodies or not tolerate heparin. The antibodies created against the heparin therapy will also bind platelets causing them to aggregate which can lead to thrombosis and thrombocytopenia.

Warfarin (Coumadin):
First off, warfarin and Coumadin are the same drug. Coumadin is just the brand name. Warfarin works by inhibiting the recycling of vitamin K. Recycling? Yeah vitamin K goes through a complex biochemical recycling process after it carboxylates factors so it can do it all over again. Warfarin blocks this recycling process, specifically it inhibits epoxide reductase. If you remember from earlier, factors 2, 7, 9, and 10 are vitamin K dependent. Warfarin therapy is monitored by the PT test.

Nerdy Note
Warfarin was first introduced in 1948 as a pesticide against rodents! Poor mice!

Enoxaparin sodium (Lovenox):
Lovenox is a low molecular weight heparin (LMWH). It binds antithrombin just like heparin. The difference between unfractionated heparin (UFH) and LMWH is complicated but the basic gist is LMWH is fractionated and has a more predictable dose response. LMWH is derived from UFH.

Tissue Plasminogen Activator (TPA):
TPA can be administered to a patient with a clot to dissolve the clot. Heparin and warfarin will prevent further clots. TPA has been mostly replaced by percutaneous coronary intervention (PCI) in the hospital.

Streptokinase:
It will convert plasminogen to plasmin but is no longer used in the United States due to better methods. It is used in some other countries due to its low cost and decent ability to bust clots.

Epsilon aminocaproic acid (EACA):
EACA is a synthetic drug that inhibits conversion of plasminogen to plasmin. It treats fibrinolytic disorders by decreasing plasmin.