The purpose of this study is to determine if post-operative administration of intrinsic pathway antagonist (TTP889) in patients on Left Ventricular Assist Device (LVAD) support will result in a 50% reduction of thrombin generation markers at 28 days compared to placebo.

Inclusion Criteria:

• Signed informed consent, release of medical information, and HIPAA forms
• Age greater than or equal to 18 years
• Male, postmenopausal female, or female who may become pregnant but is using adequate contraceptive precautions (defined as oral contraceptive, intrauterine devices, surgical contraception or a combination of a condom and a spermicide), with negative pregnancy test
• Implanted with an FDA-approved LVAD (for BTT or DT indication, e.g. HeartMate® XVE) within 72 hours prior to randomization, and able to receive the first dose of study drug by 72 hours (+6 hours) post LVAD implantation
• Post-op hemostasis adequate for starting low level anticoagulation (as assessed by surgeon)
• Extubated and able to take oral medication

Exclusion Criteria:

• Evidence of active bleeding within 24 hours prior to randomization
• History of a platelet disorder, including but not limited to thrombocytopenia and thrombasthenia
• Thrombocytopenia with platelets <80,000/ml within 48 hours prior to randomization
• History of an inherited or acquired coagulation disorder
• Hemoglobin <8 g/dL (4.85 mmol/L) or hematocrit <26% within 24 hours prior to randomization
• Clinical indication for (or the intention to use) standard anticoagulation therapy at time of randomization (e.g., atrial fibrillation or DVT)
• Intention to treat with more than 325 mg aspirin daily
• Any clinical requirement or intention to treat with phenytoin, tolbutamide or warfarin post randomization
• RVAD support at the time of randomization
• Estimated glomerular filtration rate (GFR) ≤30 ml/min (by Cockcroft-Gault formula), or any form of dialysis within 48 hours prior to randomization
• Evidence of intrinsic hepatic disease as defined as biopsy proven liver cirrhosis; or liver enzyme values (AST or ALT) that are >3 times the upper limit of normal; or Total Bilirubin >1.5 times the upper limit of normal (with the exception of Gilbert's Syndrome) within 3 days prior to randomization
• Active systemic infection, in the judgment of the investigator, within 3 days prior to randomization
• Stroke or transient ischemic attack (TIA) within 6 months prior to randomization
• History of intracranial hemorrhage or gastrointestinal bleed within 3 months prior to randomization
• Alzheimer's disease, or any other form of irreversible dementia
• History of psychiatric disease (including drug or alcohol abuse) that may impair compliance with the study protocol
• Pregnant or breastfeeding at time of randomization
• Received investigational intervention within 30 days prior to randomization
• Body weight < 45 Kg