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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: Argatroban and warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients scheduled for CABG (males or non-pregnant females) > 18 years old with at least one vein graft planned Able to provide written informed consent 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heparin PF4 antibody positive -Drug (argatroban and warfarin)<br>Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive argatroban and warfarin | Drug: Argatroban and warfarin<br>* 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.<br>|
| No Intervention: Heparin PF4 antibody positive no drug<br>Post-CABG heparin PF4 antibody positive with no signs or symptoms of HIT randomized to receive no medication | |
| No Intervention: Heparin PF4 antibody negative<br>Post-CABG heparin PF4 antibody negative with no signs or symptoms of HIT randomized to receive no medication | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary Artery Bypass Vein Graft Patency | Vein graft patency as measured by computed tomography | Approximately 30 Days post CABG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Bleeding Events. | Intracranial bleed or any clinically overt sign of hemorrhage that is associated with a fall in hemoglobin > 5 g/dL. | At 2weeks post CABG |