Alternatively Spliced Human Tissue Factor and Thrombotic Tendencies in Hemodialysis Patients

Background and Aims: Chronic hemodialysis (HD) patients are associated with an increased thrombotic tendency, a frequent and costly cause of morbidity in this patient population. HD patients often have multiple defects in their hematologic/coagulation factors; however, few convincing associations have been made between these abnormalities and clinical thrombotic events. Alternatively spliced human tissue factor (asHTF), a recently discovered soluble form of tissue factor (TF), circulates in blood and exhibits procoagulant activity. Therefore, the present investigation was designed to initially determine if asHTF levels are correlated to thrombotic tendencies in HD patients. Methods: Pre-dialysis blood samples were drawn from a cohort of 84 hemodialysis patients immediately prior to dialysis. Plasma asHTF levels were quantified and then compared to a variety of patient parameters collected for each patient. Results: Mean plasma asHTF levels for HD patients varied significantly compared to 30 healthy normal subjects. We found a positive correlation between asHTF concentration and access thrombosis in hemodialysis patients (r=0.31, p=0.0046). When patients without any episodes of thrombosis were excluded, correlation increased (r=0.59, p=0.0001). The patient with the highest number of incidences of thrombosis (n=25) also had the highest plasma asHTF concentration (1066.61 pg/ml), over seven standard deviations above the mean. Conclusions: These initial results suggest that plasma asHTF antigen levels may be associated with access thrombosis in HD patients. Further studies are needed to confirm our findings and to determine whether elevated asHTF levels indicate a causal or responsive role in HD associated access thrombosis.