Significance of Antibodies to Heparin/Platelet Factor 4 Complex in Vein Graft Patency and Potential Role of Argatroban for Prevention of Vein Graft Occlusion
Condition: Coronary Artery Bypass Graft Surgery; Presence of Heparin/Platelet Factor 4 Antibody
Intervention: Argatroban and warfarin
Intervention description: Subjects with the presence of heparin PF4 antibodies without signs or symptoms of HIT post CABG will be randomized to receive argatroban and warfarin or no drug for one month.
Intervention MeSH terms: Warfarin; Argatroban
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Heparin/Platelet Factor 4 (PF4) antibody testing will be performed in subjects who have just
      undergone coronary artery bypass grafting (CABG) surgery. 30 subjects with a positive
      antibody result and no signs or symptoms of Heparin Induced Thrombocytopenia (HIT) will be
      randomized to receive argatroban and warfarin. 30 subjects with a positive antibody result
      and no signs or symptoms of HIT will be randomized to receive no treatment. 30 subjects with
      a negative antibody result will also be followed in the study. All subjects will have a
      cardiac CT scan at about 30 days post surgery to measure the patency of their coronary artery
      bypass vein grafts. This study will evaluate if treating patients who have heparin PF4
      antibodies post-CABG with argatroban and warfarin has any effect on the short-term patency of
      coronary artery bypass vein grafts.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients scheduled for CABG (males or non-pregnant females)

          2. > 18 years old with at least one vein graft planned

          3. Able to provide written informed consent

        Exclusion Criteria:

          1. Patients who, in the investigator's or attending surgeon's opinion, are unsuitable for
             anticoagulation due to their clinical status

          2. Documented history of allergy to iodinated contrast media, warfarin, or argatroban

          3. Chronic renal impairment with CrCl<60 ml/min

          4. Recent bleeding episode

          5. Congestive Heart Failure (EF< 30%)

          6. Bleeding diathesis or known thrombophilic disorder

          7. Atrial fibrillation or other condition requiring anticoagulation at the time of
             enrollment

          8. Documented history of heparin induced thrombocytopenia

          9. Clinical suspicion of HIT at the time of randomization, defined as 50% decrease in
             Platelet count from last heparin exposure or Platelet count <100,000/ml

         10. Hepatic dysfunction (defined as LFTs > 3 times the upper limit of normal)

         11. Patients with a history of bleeding complications post-CABG

         12. Hemorrhagic stroke

         13. Gastrointestinal bleeding

         14. Requirement for fresh frozen plasma

         15. Recent central nervous system or ophthalmic surgery

         16. Aneurysm

         17. History of psychosis or senility

         18. Malignant hypertension

         19. Clinically significant pericarditis or pericardial effusion

         20. Bacterial endocarditis

         21. Hematocrit < 24%

         22. Valve replacement or repair at time of CABG

         23. Subjects with signs or symptoms of possible Transient Ischemic Attack or stroke