The anticoagulant effect of heparin and LMWH low moleculsar weight heparin is enhanced by antithrombin.

The half-life of antithrombin is altered by concomittant treatmentdue to alaterd antithrombin turnover Therefore concurent admin of thrombin with heparin or other anticoagulants that use antithrombin to exert their anticoagulant effect must be carefully monitored.

To avoid excessive anticoagulation regular coagulation tests (a PTT, and where appropriate , anti-Factor Xa activity) are to be performed at close intervals with adjustments of dosage of anticoagulant as necessary.

Treatment of thromboembolic events in heriditary thrombin deficient patients

The serious advese reaction reported in clinical studies is hemorrhage ( intra-abdominal, hemarthrosis and post procedural ) .

Most common adverse reaction reported at a frequency of at least 5% are haemorrhage and infusion site reactions.

Antithrombin is contraindicated in patients with known hypersenstivity to goat and goat milk proteins

Special precautions

Coagulation monitoring tests- To avoid excessive or insufficient anticoagulation, coagulation tests suitable for anticoagulant used (e.g. aPTT and anti-Factor Xa activity to be performed regularly at close intervals in particular at first hours following the start or withdrawal of antithrombin

Additionally monitor patients for occurance of bleeding or thrombosis in such situation.

Hypersenstivity reaction- Allergic -type hypersenstivity reactins are possible.

Patients must be closel monitored and carefully observed for any symptoms through the infusion period.

Patients should be informed early signs of hypersenstivity reactions, including hives, genealized urticaria, tightness of the chest, wheezing, hypotension and anaphlaxis.

Discontinue treatment if these symptoms occur.

Pregnancy- There are no adequate and well controlled studies in pregnant women Drug should be used during pregnancy only if required

Lactation- Use only if needed

Children- Safety and effectiveness in children have not been established

Elderly- Dose selection in elderly patients should be cautious, starting with a low end of the dosing range

Indication-

Treatment of thromboembolic events in heriditary thrombin deficient patients

Dosage-

Dose of antithrombin to be individualised

Surgical patients - 100-baseline AT activity level body weight (Kg) 2.3

Pregnant women - 100-baseline AT activity level  * body weight (Kg) 1.3

Maintenance-

Surgical patients - 100-baseline AT activity level  * body weight (Kg) 10.2

Pregnant women - 100-baseline AT activity level * body weight (Kg) 5.4

Pharmacology-

AT III , an alpha 2-glycoprotein of molecular weight 58,000 is normally present in human plasma at a concentration of approx. 12.5mg/dL and is the major plasma inhibitor of thrombin . Inactivation of thrombin by AT III occurs by formation of covalent bond resulting in an inactive 1:1 stochiometetric complex beteween the two, invoving an interaction of the active serine of thrombin and an arginine reactive site of AT III.

The neutralization rate of serine proteases by AT III proceeds slowly in the absence of heparin, but is greatly accelrated in the presence of heparin.

Pregnancy-

There are no adequate and well controlled studies in pregnant women Drug should be used during pregnancy only if required

Lactation-

Use only if needed

Children-

Safety and effectiveness in children have not been established

Elderly-

Dose selection in elderly patients should be cautious, starting with a low end of the dosing range