🩹 DOACs Explained: The Origin of the Name and the Meaning of “Direct”

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♦️ Anticoagulants We Encounter Most Often

In perioperative medicine, the anticoagulants that immediately come to mind are:

  • Heparin
  • Warfarin
  • DOACs (Direct Oral Anticoagulants)

♦️ DOACs — Can You Recall All the Names?

While heparin and warfarin are familiar, there are currently four major DOACs on the market. Do you know both their generic and brand names?😅

  • Dabigatran → Pradaxa®
  • Apixaban → Eliquis®
  • Rivaroxaban → Xarelto®
  • Edoxaban → Savaysa® (Lixiana® in some countries, e.g., Japan/Europe)

🔷 From NOAC to DOAC

About a decade ago, these drugs were often referred to as NOACs (Novel Oral Anticoagulants). Since they are no longer “new,” the preferred term now is DOACs (Direct Oral Anticoagulants).


🔷 But What Does “Direct” Actually Mean?

Why the word “direct”? It implies that other anticoagulants act indirectly.
To clarify, let’s briefly review how heparin and warfarin work.


♦️ How Each Anticoagulant Works

🔷 Mechanism of Action — Heparin

Heparin does not directly block clotting factors. Instead, it binds to antithrombin III (AT-III), enhancing AT-III’s activity and leading to the inactivation of thrombin (factor IIa) and factor Xa.

👉 Importantly, heparin does not inhibit the synthesis of clotting factors.


🔷 Mechanism of Action — Warfarin

Warfarin works differently. It inhibits vitamin K epoxide reductase (VKOR), thereby blocking the recycling of vitamin K. Vitamin K is essential for the γ-carboxylation (activation) of vitamin K–dependent clotting factors (II, VII, IX, and X).

As a result, these clotting factors are synthesized but remain functionally impaired. Thus, warfarin acts indirectly, not by directly binding to the clotting factors.


🔷 Then, The Main Players: DOACs

And now to the DOACs themselves:

  • DabigatranDirect thrombin (factor IIa) inhibitor
  • ApixabanFactor Xa inhibitor
  • RivaroxabanFactor Xa inhibitor
  • EdoxabanFactor Xa inhibitor

Dabigatran binds directly to thrombin’s active site, while the other three bind directly to factor Xa, thereby blocking the prothrombinase complex and reducing thrombin generation.



📝 Summay / Take-Home Message

  • Heparin: works indirectly via AT-III to inactivate IIa and Xa.
  • Warfarin: works indirectly by inhibiting VKOR, reducing activation of factors II, VII, IX, X.
  • DOACs: act directly on clotting factors.
  • Dabigatran = thrombin inhibitor.
  • Apixaban, rivaroxaban, edoxaban = factor Xa inhibitors. 👉 The key is in the name: “Direct” means direct binding to clotting factors.

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