Critically ill patients with high risk for thrombosis or tromboembolic events with the presence of heparin resistance, treated at the Department for General and Surgical Critical Care Medicine of the Medical University Innsbruck, Austria will be enrolled in the study when meeting the inclusion- and exclusion criteria. If a patient meets the inclusion criteria and is recruited for the study, the patient will be randomized either to Group A or Group H.

All patients have to achieve a prophylactic aPTT-target range of an aPTT-level of 45 - 60 sec (Pathromtin® SL) within 6 to 8 hours.

Randomisation Group A:

If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be stopped and Argatroban will be given and adjusted until the target aPTT-range is achieved.

Randomisation Group H - Standard therapy:

If a Heparin resistance appears and the patient meets the inclusion and exclu-sion criteria, he/she will be enrolled. The Heparin administration will be contin-ued and, if necessary increased. Hereby the maximum heparin dose is 1.500 IU per hour.

Therapy failure Group H:

Primary target failure at Visit 3 (6-8 hours):

If a patient of Group H does not achieve the target-aPTT within 6-8 hours, he/she will switch to Group A and will start with T1 (Baseline) and will follow the visits according to Group A until the final Visit 9 (T1 / day 30).

Maintenance failure after Visit 3:

Maintenance failure after 6-8 hours is defined as non-maintenance of the tar-get-aPTT until day 7 with a max. heparin dosage of 1.500 IU per hour. In this case, heparin therapy has to be changed to Argatroban.

The patient will start with T1 (Baseline) and will follow the visits according to Group A until the final Visit 9 (day 30) counting from the Baseline of Group A.

Therapy failure Group A:

If a patient of Group A does not achieve the target-aPTT within 6-8 hours or cannot maintain the target-aPTT in spite of reaching the maximum dosage of 10µg/kg/min during the further study period, the patient automatically drops out of the study.

The same is effective for patients who switched to the Group A after a therapy failure in Group H.

General:

Two hours after starting the Baseline investigations, patient's parameters in-cluding blood collections will be measured for the second time (T2). Additional measurements will be made at 6-8 hours (T3), 24 hours (T4), 48 hours (T5), 5 days (T6) after start of study drug and on day 7 before (T7) stop of study medication and 6h (T8) after stop of study medication. 30 days after inclusion in the study, a final investigation is planned (T9).

Inclusion Criteria:

• Patient at risk for thrombosis or thromboembolic complications with the need of prophylactic antithrombotic therapy
• Age: 18 - 85 years
• Prohylactic anticoagulation (aPTT: 45 - 60 sec) is not achieved with a heparin dosage of 1.200 IU per hour after two hours of infusion

Exclusion Criteria:

• If patient needs an aPTT-level > 60 sec for any reason
• Active bleeding
• Risk for bleeding higher than risk of thromboembolic event as anticipated by the physician
• Surgical procedure with the need for interruption of antithrombotic therapy within the next 24 hours
• Inevitable lethal course
• Severe Liver failure: Quick < 30 %
• Pregnancy
• Planned peridural or spinal anaesthesia during the study
• Patient with known refusal of a participation in this clinical trial
• Active participation in another clinical trial
• Any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study or confound the ability to interpret data from the study
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form