Effect of statin intake on FVIII levels and bleeding outcomes in hypercholesterolemic patients with hemophilia A

despite their condition of hypocoagulablity, and nowadays that life expectancy of hemophiliacs approaches that of non-hemophilic peers, cardiovascular (CV) disease represents a significant cause of morbidity and mortality also in this patient population [1]. However, since the use of either antiplatelet or anticoagulant agents associates with a relevant bleeding risk in these patients, the control of CV-risk factors, and in particular of hypercholesterolemia, becomes pivotal for primary and secondary CV prophylaxis. Low density lipoprotein (LDL) cholesterol is cleared from plasma by LDL receptors (LDLR) mainly present on liver cells. Statins, the most widely used lipid-lowering agents, act by inhibiting the enzyme hydroxymethylglutarylCoA (HMG-CoA) reductase but they also increase hepatocyte LDLR expression. FVIII is cleared from blood through the binding to several receptors including LRP1, that belongs to the LDLR family, which cooperate with LDLR in regulating its plasma levels [2]. Atorvastatin was shown to increase the hepatic expression of LRP1 [3]. Interestingly, factor VIII levels were reported to be lower in healthy subjects treated with statins compared with untreated controls [4], and a recent trial in patients with venous thrombosis showed that a brief course of high-dose rosuvastatin (20 mg/d) significantly reduced FVIII levels [5]. It can thus be hypothesized that statins may reduce FVIII levels by increasing LDLR and LRP1 [6].