No

Anticoagulant; Blood Product Derivative

Hereditary antithrombin III deficiency

C

Hypersensitivity to antithrombin III or any component

Can potentially transmit infectious diseases since it is a product of human plasma. Discuss risk versus benefits with patient. Reduce the dose of heparin to avoid bleeding when used concurrently. Administer alone by the I.V. route only.

1% to 10%: Central nervous system: Dizziness (2%)

<1% (Limited to important or life-threatening symptoms): Lightheadedness, fever, chest tightness, chest pain, vasodilatory effects, edema, urticaria, fluid overload, nausea, foul taste in mouth, cramps, bowel fullness, hematoma formation, film over eye, diuretic effects, shortness of breath, thrombocytopenia, abdominal cramps, hives

Levels of 150% to 200% have been documented in patients with no signs or symptoms of complications

Drugs which affect platelet function (eg, aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel) may potentiate the risk of hemorrhage.

Heparin's anticoagulant effects are potentiated by antithrombin III.

Thrombolytic agents increase the risk of hemorrhage.

Warfarin (and other oral anticoagulants) may increase the risk of bleeding with antithrombin III.

Reconstitute with 10 mL sterile water for injection, normal saline or D₅W; do not shake; stability of I.V. admixture: 24 hours at room temperature; do not refrigerate

Antithrombin III is the primary physiologic inhibitor of in vivo coagulation. It is an alpha₂-globulin. Its principal actions are the inactivation of thrombin, plasmin, and other active serine proteases of coagulation, including factors IXa, Xa, XIa, XIIa, and VIIa. The inactivation of proteases is a major step in the normal clotting process. The strong activation of clotting enzymes at the site of every bleeding injury facilitates fibrin formation and maintains normal hemostasis. Thrombosis in the circulation would be caused by active serine proteases if they were not inhibited by antithrombin III after the localized clotting process. Patients with congenital deficiency are in a prethrombotic state, even if asymptomatic, as evidenced by elevated plasma levels of prothrombin activation fragment, which are normalized following infusions of antithrombin III concentrate.

Adults: After first dose of antithrombin III, level should increase to 120% of normal; thereafter maintain at levels >80%. Generally, achieved by administration of maintenance doses once every 24 hours. Initially and until patient is stabilized, measure antithrombin III level at least twice daily, thereafter once daily and always immediately before next infusion. 1 unit = quantity of antithrombin III in 1 mL of normal pooled human plasma; administration of 1 unit/1 kg raises AT-III level by 1% to 2%; assume plasma volume of 40 mL/kg.

Measure antithrombin III preceding and 30 minutes after dose to calculate in vivo recovery rate; maintain level within normal range for 2-8 days depending on type of surgery or procedure.

Monitor antithrombin III levels during treatment period

Maintain antithrombin III level in plasma >80%

None reported

None reported

No information available to require special precautions

No effects or complications reported

This medication can only be given I.V. Report sudden onset headache, rash, chest or back pain, or respiratory difficulties. Future safety: Wear some identification that you have a hemophilic condition. Pregnancy/breast-feeding precautions: Consult prescriber if pregnant or breast-feeding.

Infuse over 5-10 minutes; rate of infusion: 50 units/minute (1 mL/minute) not to exceed 100 units/minute (2 mL/minute)

Powder for injection: 500 units (50 mL)

Collen D, "Treatment of Disseminated Intravascular Coagulation," Bibl Haematol, 1983, 49:295-305.

Humphries JE, "Thrombophilia and Complex Acquired Deficiencies of Antithrombin, Protein C, and Protein S," Semin Hematol, 1995, 32(4 Suppl 2):8-16.

Vinazzer H, "Clinical Use of Antithrombin III Concentrates," Vox Sang, 1987, 53(4):193-8.

Wheeler A and Rubenstein EB, "Current Management of Disseminated Intravascular Coagulation," Oncology, 1994, 8(9):69-73.