A Study of Safety, PK, & PD of ISIS 416858 Administered Subcutaneously to Patients With End-Stage Renal Disease on Hemodialysis

Inclusion Criteria: * End stage renal disease maintained on outpatient hemodialysis at a healthcare center for \> 3 months from screening with hemodialysis using heparin (unfractionated heparin or low-molecular weight heparin) 3 times per week for a minimum of 3 hours per dialysis session and plan to continue this throughout the study. Exclusion Criteria: * Documented thrombotic event (acute coronary syndrome, stroke or transient ischemic attack, venous thromboembolic event) in the past 3 months. * Active bleeding within the past 3 months from screening or documented bleeding diathesis (history of bleeding disorder) or Screening values of: * Platelet count \< 150,000 cells/mm3 * INR \> 1.4 * aPTT \> upper limit of normal (ULN) * Abnormal liver function at Screening: * ALT or AST \> 2 x ULN * Total bilirubin \> ULN * Concomitant medication restrictions: Concomitant use of anticoagulant/antiplatelet agents (e.g., dabigatran, rivaroxaban, clopidogrel) that may affect coagulation (except low dose aspirin (≤ 100 mg/day) during Treatment and Post-treatment Evaluation Periods is not allowed. * Uncontrolled hypertension as judged by the Investigator. Patients with a pre- or post-dialysis blood pressure (BP) that is \> 160 mmHg on at least 3 of last 5 dialysis treatments. * Planned major surgery in the next 6 months (e.g. renal transplant surgery)