Safety, Pharmacokinetics and Efficacy of an AT-III Concentrate.

This study will be a prospective, unblinded, non-randomized, open-label, multi-center Phase
II/III study with 2 segments, i.e. a PK evaluation (Segment I), and an assessment of
prophylaxis in surgical interventions and pregnancy/delivery, (Segment II). During the PK
segment, the subjects would remain on their current anticoagulation therapy except for
subjects on heparin therapy where a wash-out period of at least 5 half lives would be
required. In total, 15 subjects with congenital ATIII Deficiency will be enrolled for the PK
assessment (Segment I).

For Segment II, fifteen episodes will be treated. Recruitment of individual subjects with
high risk for venous thrombosis for Segment II of this study is necessary because of the
rarity of Antithrombin deficiency in the population.

Inclusion Criteria:

- Congenital ATIII deficiency documented by determination of plasma levels of ATIII off
all therapies. Specifically, the baseline levels of ATIII activity should be equal to
or less than 60%.

- Age > 12 years with a body weight of no less than 30 kg.

- Have not participated in another investigational study for at least 30 days For
Segment II, enrollment requires a pregnancy/delivery or a surgical procedure (it
should be a major surgery although data from a minor surgery will also be collected).

- Documented personal history of major thromboembolic or thrombotic event.

- Male or female

- HIV, HBV, HCV, HAV and PARVO B19 status known prior to entry.

- The subject is willing to comply with all aspects of the protocol, including blood
sampling, for the duration of the study.

- The subject has signed an informed consent form (if at least 18 years old), or the
subject's parent or legal guardian has signed the informed consent form. Subjects
below the age of 18 years will also be asked to sign an assent form. All consent and
assent forms must be approved in advance by the Institutional Review Board of the
investigator's institution.

- Patients with heparin-associated thrombocytopenia who require anticoagulation with
non-heparin containing drugs will be eligible if they can be safely transitioned
during the washout period for the Segment I PK study.

- If pregnant, a woman must be Parvo B19 IgG antibody positive.

Exclusion Criteria:

- Acquired deficiency of ATIII

- Receiving concomitant treatment for thrombophilic disorders other than ATIII
deficiency

- Inability or unwillingness to comply with the protocol requirements

- History of anaphylactic reaction(s) to blood or blood components

- Allergies to excipients.

- Liver function tests >/= 2.5 X ULN

- Serum creatinine >1.2 X ULN

- Urine >/= 2+ protein with urine dipstick test.

- The subject is known to have abused alcohol or illicit drugs within the past 12
months.

- The subject is unlikely to adhere to the protocol requirements of the study or is
likely to be uncooperative or unable to provide a storage serum sample at the
screening visit.

- Patients on heparin-treatment who, for clinical reasons, cannot safely be
discontinued from heparin therapy during the PK segment.