GTC Biotherapeutics (fka GTCB)

[DewDiligence]

A Quick Primer on How Antithrombin
Differs from Other Anticoagulants

The name antithrombin is a misnomer because antithrombin does much more than inhibiting thrombin, also known as FIIa. Antithrombin also inhibits FXa, which plays a major role in the production of thrombin by serving as the pivot point of a feedback loop in the coagulation cascade (#msg-26899675).

To a lesser degree, antithrombin inhibits FVIIa, FIXa, FXIa, and FXIIa; however, its main anticoagulation function of medical consequence is inhibiting FIIa and FXa.

As a general rule of thumb, FIIa inhibition is needed for treating or preventing arterial thrombosis, and FXa inhibition is needed for treating or preventing venous thrombosis and pulmonary embolism. Thus, drugs that inhibit both FIIa and FXa tend to be suited to a wider range of indications than drugs that treat only one of them.

There are many drugs that inhibit FIIa, FXa, or both; these include Angiomax, Pradaxa, Arixtra, low-molecular-weight heparins such as Lovenox, unfractionated heparin, and various drugs in development such as Xarelto, Apixaban, and MNTA’s M118 (#msg-26900300).

(Please see #msg-28231619 for an index to information on various anticoagulants on the market or in development.)

All of the above drugs with the exception of Angiomax and Pradaxa—which are known as direct thrombin inhibitors—require antithrombin in order to work. This is because a bound complex of antithrombin and endogenous heparin is what actually inhibits FIIa and/or FXa. If a patient has either hereditary or acquired antithrombin deficiency, the antithrombin-heparin complex is not formed in sufficient quantity and FIIa and FXa are not inhibited.

Apart from the above discussion of its anticoagulant properties, antithrombin has anti-inflammatory properties that may be of great consequence in treating such conditions as DIC/sepsis (#msg-27215812, #msg-25480768).