Stacy E Croteau1, Andrew L Frelinger2, Anja J Gerrits2, Alan D Michelson2. 1. Boston Hemophilia Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Center for Platelet Research Studies, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Bleeding phenotypes among individuals with severe factor VIII (FVIII) deficiency are variable, even with routine prophylactic FVIII administration. Activated platelets, in addition to their role in primary hemostasis, play a major role in coagulation by providing a phospholipid surface to which coagulation factors bind. OBJECTIVES: The aim of this study was to determine whether platelet function is associated with past and/or future bleeding in patients with severe FVIII deficiency on prophylaxis. PATIENTS/ METHODS: Platelet function quantified by platelet surface expression of phosphatidylserine, platelet surface glycoprotein (GP) VI, platelet surface activated GPIIb-IIIa, platelet surface P-selectin, the percentage of coated platelets, and the percentage of platelet-derived microparticles in the presence or absence of in vitro activation by various agonists was assessed in 34 patients. RESULTS: Decreased platelet surface phosphatidylserine expression (identified by annexin V binding), both in the presence and absence of ADP/thrombin receptor activating peptide, demonstrated a significant association with both prior and subsequent bleeding in any location and specifically with hemarthrosis. No significant difference between patients with and without bleeding was observed in any of the other platelet activity markers. CONCLUSIONS: Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.
BACKGROUND:Bleeding phenotypes among individuals with severe factor VIII (FVIII) deficiency are variable, even with routine prophylactic FVIII administration. Activated platelets, in addition to their role in primary hemostasis, play a major role in coagulation by providing a phospholipid surface to which coagulation factors bind. OBJECTIVES: The aim of this study was to determine whether platelet function is associated with past and/or future bleeding in patients with severe FVIII deficiency on prophylaxis. PATIENTS/ METHODS: Platelet function quantified by platelet surface expression of phosphatidylserine, platelet surface glycoprotein (GP) VI, platelet surface activated GPIIb-IIIa, platelet surface P-selectin, the percentage of coated platelets, and the percentage of platelet-derived microparticles in the presence or absence of in vitro activation by various agonists was assessed in 34 patients. RESULTS: Decreased platelet surface phosphatidylserine expression (identified by annexin V binding), both in the presence and absence of ADP/thrombin receptor activating peptide, demonstrated a significant association with both prior and subsequent bleeding in any location and specifically with hemarthrosis. No significant difference between patients with and without bleeding was observed in any of the other platelet activity markers. CONCLUSIONS: Decreased platelet surface phosphatidylserine expression measured by annexin V binding predicts increased bleeding in severe FVIII deficient patients on prophylaxis.