Antithrombin III is a natural anticoagulant protein, capable of inactivating thrombin, activated factor 9, activated factor 10, and other activated coagulation factors. Heparin accelerates the inactivation of activated factors by antithrombin III. Patients with decreased levels of antithrombin III may show a hypercoagulable state. A deficiency in antithrombin III can be congenital or acquired. Infusion of a plasma product containing antithrombin III can prevent thrombotic events.


Antithrombin III:

(1) plasma concentration normally about 12.5 mg/dL

(2) one unit of antithrombin III activity is that seen in 1 mL of normal plasma

(3) plasma levels are usually expressed as percent of normal activity, where 100% indicates 1 unit of activity per mL

(4) half-life of about 48 hours


Features of congenital antithrombin III deficiency:

(1) autosomal dominant inheritance

(2) frequency approximately 1 in 2,000-5,000

(3) onset of venous thrombosis at young age

(4) family history of venous thromboembolism

(5) occurrence of thrombosis in unusual sites

(6) thrombosis resistant to heparin therapy

(7) thrombosis during pregnancy, following surgery, with trauma or after infection

(8) fatal thrombosis can occur in newborns


Conditions associated with acquired decrease in antithrombin III levels:

(1) DIC

(2) cirrhosis

(3) nephrotic syndrome (with significant proteinuria)

(4) oral contraceptive use

(5) estrogen therapy

(6) L-asparaginase therapy


Replacement sources:

(1) fresh frozen plasma: each mL contains 1 unit of activity

(2) thrombate III (Bayer): a concentrate prepared from pooled plasma, with heat inactivation and purification steps


units of antithrombate required =

= ((desired antithrombin III level) - (current antithrombin III level)) * (body weight in kilograms) / 1.4



• antithrombin III level is percent activity, as a whole number

• volume infused is 1 mL for every 50 units of activity administered


Goals of replacement therapy:

(1) The initial dose should raise antithrombin III levels to 120%.

(2) A maintenance dose is administered every 24 hours to maintain the antithrombin III level in the 80-120% range.

(3) Plasma level monitoring is usually performed every 12 hours after initial dose, but may be done more frequently.


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