To identify novel biomarkers for thrombosis of vascular access.
To compare platelet aggregation of dialysis patients who have had access thrombosis with those who have not.
The platelets of patients who thrombose their access are hyperreactive to aggregation stimuli compared to the platelets of patients who do not. Platelet aggregation assays may offer a way to identify those who would benefit from anti-platelet therapy to prolong access life.
Burden of Vascular Thrombosis: Vascular access dysfunction is responsible for ¼ of dialysis patient hospitalizations and costs about 1 billion dollars per year. The most common cause of vascular access dysfunction is thrombosis, with 50% of AV grafts thrombosing within 2 years.
Numerous studies have been conducted to determine the etiology of vascular thrombosis. The foci of these experiments have included stenosis and TGF-1 and PAI-1, thrombophilias, anticardiolipin antibody, hyperhomocyteinemia and systemic disorders such as SLE. Recently, more attention has been directed towards the role of platelets.
Dember et. al. conducted a randomized controlled trial of clopidogrel vs. placebo administered after fistula creation in a large group of patients with either chronic kidney disease (CKD) or end stage renal disease (ESRD). At 6 weeks 12.2% of the clopidogrel group had thrombosed their fistulas vs. 19.5% of the placebo group. Dixon et. al. randomized 649 participants to either dipyridamole plus aspirin or placebo over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% in the placebo group and 28% in the dipyridamole-aspirin group, with an absolute difference of 5%. Although both trials demonstrated decreased incidence of arteriovenous (AV) access thrombosis with anti-platelet agents, there is reluctance to use these agents. Concerns include the increased incidence of bleeding in uremic patients. Consequently, right now there are no good means of preventing AV access thrombosis.
This study will expand on previous studies by using a panel of sensitive platelet activation tests, as opposed to one or two, to determine if the platelets of participants who thrombose their AV access are hyperreactive compared to the platelets of participants who do not. Unlike the previous studies, we will also compare platelet parameters of chronic kidney disease (CKD) participants as controls, and exclude patients with known coagulation disorders, such as SLE, thrombophilias, or nephritic syndrome. Data from this study will allow to design a prospective trial to evaluate the predictive value of this sensitive platelet activity panel and identify those that will benefit from anti-platelet agents. This pilot study will also serve as the basis for an NIH grant application.
This will be a case-control pilot study, comparing platelet reactivity of ESRD patients who have a history of AV access thrombosis to those who do not, as well as control groups of chronic kidney disease patients not on dialysis, using a validated panel of platelet function tests developed by Dr. Jeffrey Berger.