antithrombin III

antithrombin /an·ti·throm·bin/ (-throm´bin) any naturally occurring or therapeutically administered substance that neutralizes the action of thrombin and thus limits or restricts blood coagulation.

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antithrombin I  fibrin, referring to its capacity to adsorb thrombin and thus neutralize it.

antithrombin III  a plasma α of the serpin family that inactivates thrombin and also inhibits certain coagulation factors and kallikrein. Inherited deficiency is associated with recurrent deep vein thrombosis and pulmonary emboli; the complications are prevented and treated with a preparation of antithrombin III from pooled human plasma.

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antithrombin III, human (AT-III, heparin cofactor 1)

Thrombate III

Pharmacologic class: Blood derivative, coagulation inhibitor

Therapeutic class: Antithrombin

Pregnancy risk category B

Action

Inactivates thrombin and activated forms of factors IXa, Xa, XIa, and XIIa, thereby inhibiting coagulation and thromboembolism formation

Availability

Injection: 500 international units, 1,000 international units

⊘Indications and dosages

➣ Thromboembolism related to AT-III deficiency

Adults: Initial dosage is individualized to amount required to increase AT-III activity to 120% of normal (determined 20 minutes after administration). Usual infusion rate is 50 to a maximum of 100 international units/minute I.V. Dosage calculation is based on anticipated 1.4% increase in plasma AT-III activity produced by 1 international unit/kg of body weight.

Use this formula to calculate dosage: Required dosage (international units) equals desired activity (%) minus baseline AT-III activity (%) multiplied by weight (kg) divided by 1.4 (international units/kg).

Maintenance dosage is individualized to amount required to maintain AT-III activity at 80% of normal.

Contraindications

None

Precautions

Use cautiously in:
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Reconstitute drug concentrate with 10 ml of sterile water, normal saline solution, or dextrose 5% in water.
• Use filter needle provided by manufacturer to draw up solution.
• Don't shake vial.
• Know that drug may be diluted further in same solution if desired.
• Don't mix with other solutions.
• Infuse over 10 to 20 minutes.
• Administer within 3 hours of reconstitution.
☞ If adverse reactions occur, decrease infusion rate or, if indicated, stop infusion until symptoms disappear.

Route	Onset	Peak	Duration
I.V.	Immediate	Unknown	4 days

Adverse reactions

CNS: dizziness, light-headedness, headache

CV: vasodilation, reduced blood pressure, chest pain

EENT: perception of "film" over eyes

GI: nausea, sensation of intestinal fullness

GU: diuresis

Musculoskeletal: muscle cramps

Respiratory: dyspnea, shortness of breath

Skin: urticaria, oozing lesions, hives, hematoma

Other: foul taste, chills, fever

Interactions

Drug-drug. Heparin: increased anticoagulant effect

Patient monitoring

• Monitor AT-III activity levels regularly.
☞ Watch for signs and symptoms of too-rapid infusion, such as dyspnea and hypertension.
• Monitor vital signs and temperature.
• Assess fluid intake and output to detect dehydration.

Patient teaching

☞ Instruct patient to immediately report chest tightness, dizziness, and fever.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to minimize GI upset and unpleasant taste by eating small, frequent servings of healthy food and drinking plenty of fluids.
• Tell patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.

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antithrombin III

Hematology A 58 kD α₂-glycoprotein with a single polypeptide chain that inactivates serine proteases–thrombin and other coagulation proteins including factor Xa, IXa, kallikrein and others by an irreversible heparin-dependent reaction Function AT III dissolves blood clots that normally form within the circulation; heparin's anticoagulant activity hinges on activation of AT-III; AT-III-deficient individuals do not benefit from heparin therapy; ↓ AT-III may be a congenital AD condition, or acquired, occurring in DIC–due to 'consumption' or in liver disease–due to ↓ AT-III production, resulting in an ↑ risk of coagulation; AT III is ↓ in congenital deficiency, liver transplant, DIC, nephrotic syndrome, cirrhosis, chonic liver disease, carcinoma, mid-menstrual cycle; AT III is defective in 0.14% to 0.5% of the general population. See Hereditary thrombophilia, Recombinant human antithrombin III.