Significance of Antibodies to Heparin/Platelet Factor 4 Complex in Vein Graft Patency and Potential Role of Argatroban for Prevention of Vein Graft Occlusion

Phase 4

Terminated

Conditions: Presence of Heparin/Platelet Factor 4 Antibody
Coronary Artery Bypass Graft Surgery

Brief 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.

Detailed Description: This is a prospective, randomized, single center study. Patients scheduled for CABG will be screened and enrolled. Subjects positive for heparin/PF4 antibody within 24 h after CABG and without clinical suspicion of HIT will be randomized into one of two groups. An additional 30 patients with negative antibody titers will serve as a control group.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Patients who, in the investigator's or attending surgeon's opinion, are unsuitable for anticoagulation due to their clinical status
Documented history of allergy to iodinated contrast media, warfarin, or argatroban
Chronic renal impairment with CrCl<60 ml/min
Recent bleeding episode
Congestive Heart Failure (EF< 30%)
Bleeding diathesis or known thrombophilic disorder
Atrial fibrillation or other condition requiring anticoagulation at the time of enrollment
Documented history of heparin induced thrombocytopenia
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
Hepatic dysfunction (defined as LFTs > 3 times the upper limit of normal)
Patients with a history of bleeding complications post-CABG
Hemorrhagic stroke
Gastrointestinal bleeding
Requirement for fresh frozen plasma
Recent central nervous system or ophthalmic surgery
Aneurysm
History of psychosis or senility
Malignant hypertension
Clinically significant pericarditis or pericardial effusion
Bacterial endocarditis
Hematocrit < 24%
Valve replacement or repair at time of CABG
Subjects with signs or symptoms of possible Transient Ischemic Attack or stroke

Arm && Interventions

Group	Intervention	Description
Heparin PF4 antibody positive -Drug (argatroban and warfarin)	Argatroban and warfarin	Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin

Primary Outcome Measures

Name	Time	Method
Coronary Artery Bypass Vein Graft Patency	Approximately 30 Days post CABG	Vein graft patency as measured by computed tomography

Secondary Outcome Measures

Name	Time	Method
Major Bleeding Events.	At 2weeks post CABG	Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin \> 5 g/dL.