Direct thrombin inhibitors

Direct thrombin inhibitor

A class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin (factor II).

Several members of the class are replacing heparin and derivatives, and warfarin in various clinical scenarios.

There are three types of direct thrombin inhibitors, dependent on their interaction with the thrombin molecule.

Bivalent DTIs, hirudin and analogs, bind both to the active site and exosite 1,

Univalent DTIs bind only to the active site.

The third class of inhibitors is the allosteric inhibitors.


Hirudin and derivatives.








Melagatran, and its prodrug ximelagatran



Thrombin demonstrates a high level of allosteric regulation, and allosterism in thrombin is regulated by the exosites 1 and 2 and the sodium binding site.

Allosteric inhibitors may provide a more regulatable anticoagulant, but no allosteric thrombin inhibitor has still reached the stage of clinical trials.

Bivalent use limited to circumstances where heparin would be indicated such as the acute coronary syndrome but cannot be used.

Bivalent agents are administered by injection intravenous, intramuscular or subcutaneous injection and are less suitable for long-term treatment.

Argatroban is used for heparin-induced thrombocytopenia, requires anticoagulation but not with heparin.

There is no therapeutic drug monitoring widely available for DTIs.

The ecarin clotting time, although not in general clinical use, would be the most appropriate monitoring test.

Include lepirudin, argatroban and bivalirudin.

Lepirudin usage in patients with renal insufficiency with creatinine clearance >30 cc/min but greater than 60 cc/min should be monitored using the activated partial thromboplastin time, and the dose reduced.

In patients receiving argatroban being transitioned to a vitamin K antagonist, it is recommended to utilize factor X levels to adjust the dose of the vitamin K antagonist.

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