Venous thromboembolism, factor VIII and chronic kidney disease

Chronic kidney disease (CKD) affects 30 million Americans and is associated with approximately a two-fold increased risk of venous thromboembolism (VTE). There is a graded increased risk of VTE across declining kidney function, as measured by estimated glomerular filtration rate (eGFR) and albuminuria. When patients with end-stage kidney disease (ESKD) experience VTE they are more likely than the general population to be hospitalized and they have a higher mortality. The incidence and consequences of VTE may also differ depending on the cause of kidney disease. In addition, kidney transplant patients with VTE are at a greater risk for death and graft loss than transplant patients without VTE. The reasons that patients with CKD are at increased risk of VTE are not well understood, but recent data suggest that factor VIII is a mediator. Factor VIII is an essential cofactor in the coagulation cascade and a strong risk factor for VTE in general. It is inversely correlated with eGFR and prospective studies demonstrate that factor VIII activity predicts incident CKD and rapid eGFR decline. The etiology of CKD may also influence factor VIII levels. This review summarizes the epidemiology VTE in CKD and reviews the biochemistry of factor VIII and determinants of its levels, including von Willebrand factor and ABO blood group. We explore mechanisms by which the complications of CKD might give rise to higher factor VIII and suggests future research directions to understand how factor VIII and CKD are linked.