antithrombin III, human

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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.

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.

References in periodicals archive ?
Tatarsky, "Prophylaxis of thromboembolism during pregnancy in hereditary AT-III deficiency," American Journal of Hematology, vol.
(1990) AT-III concentrate Total 14,563 IU for 5 d Pt2 Total 17,355 IU for 7 d Hellgren et Case series Pt1 Plasma-derived al.
Coagulation factors, protein C, protein S, and AT-III were evaluated by automated analyzer system (AMAX-200 automated analyzer, Trinity Biotech, Ireland).
reported that taking typical antipsychotic group had significantly higher AT-III levels, but fibrinogen levels did not differ between the groups: they suggested that the observed abnormalities were not related to a direct drug effect (olanzapine) [12].
Decreases in circulating natural anticoagulants, protein C (2), (3), (4), (5), (6), protein S (3), ve AT-III (5) and an increase in fibrinogen (5) have been shown to occur following SCT, which cause a hypercoagulable state, a risk factor associated with thromboembolic events post transplantation.
Decreased natural anticoagulants (protein S, protein C, and AT-III) (2-6)
It has been reported that presence of some types of autoantibodies are associated with Th1 cytokine profile; which among them are ANA in patients with Sjogren's syndrome (6), rheumatic diseases (7) and multiple sclerosis (8), anti-dsDNA in NZB/W F1 lupus-prone mice (9), APA in recurrent spontaneous abortions (10), TgAbs in Graves' disease (11), TPOAbs in Hashimoto's thyroiditis (12) and thyroid-associated ophthalmopathy (13) and AT-III Abs in spontaneous abortion (14).
The patients were screened by a battery of immunological tests including ANA, anti-dsDNA, LACAbs, APA, ACA, TgAbs, TPOAbs and AT-III Abs and cases with one or more positive results for these autoantibodies were categorized as the IRA group.
Kits used in this study were purchased from the following companies: Leptin ELISA (BioVendor, Czech Republic), APA and ACA ELISA (Orgentech Diagnostica GmbH, Mainz, Germany), ANA and anti-dsDNA ELISA (Aesku Diagnostics, Wendelsheim, Germany), TgAbs and TPOAbs CLEIA (DiaSorin, Antony, France), AT-III Abs, and LACAbs CLEIA (Diag nostica Stago, Asnieres, France).
Antithrombin-III (AT-III) is a natural occurring inhibitor of blood coagulation and plays an important part in maintaining blood in the fluid state.
Antithrombin III (AT-III) deficiency is the most commonly inherited anticoagulant deficiency, and MVT is a relatively common presentation of AT-III deficiency.(9) Antithrombin III exerts 50% of the serum's intrinsic anticoagulant activity by inhibiting thrombin and factor Xa.
In the absence of mechanical or infectious causes for MVT, assays for AT-III, protein C, and protein S should be done as the findings have relevance for the health of the patient's offspring.