Abstract Number: PB0846
Meeting: ISTH 2020 Congress
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 for assembly of the prothrombinase complex, thereby greatly enhancing the rate of thrombin generation.
Aims: To determine whether platelet function is associated with past and/or future bleeding in patients with severe FVIII deficiency receiving FVIII prophylaxis.
Methods: Following IRB-approved, written informed consent, platelet function in the presence or absence of in vitro activation by various agonists was assessed in 34 patients (median age 12.6 years) by multiple end points: 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. A clinically significant bleeding episode was defined as one that required clinical intervention or pharmacotherapy such as additional FVIII replacement or antifibrinolytic agents. Laboratory investigators were blinded to clinical findings and clinical investigators were blinded to laboratory findings until completion of data collection.
Results: Decreased platelet surface phosphatidylserine expression (identified by geometric mean fluorescence of annexin V binding), both in the presence and absence of adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP), demonstrated a significant association with both prior and subsequent bleeding in any location and also specifically with joint bleeds (Figure). No significant difference between patients with and without bleeding was observed for any of the other endpoints.
Conclusions: Lower platelet surface phosphatidylserine expression (as measured by annexin V binding to platelets) is associated with prior bleeding and, more importantly, is predictive of future bleeding in patients with severe FVIII deficiency receiving FVIII prophylaxis. A larger, multicenter study is needed to confirm the clinical utility of platelet surface phosphatidylserine as a biomarker for future bleeding.
To cite this abstract in AMA style:Frelinger III AL, Croteau SE, Gerrits AJ, Michelson AD. Decreased Platelet Surface Phosphatidylserine Predicts Increased Bleeding in Patients with Severe Factor VIII Deficiency [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/decreased-platelet-surface-phosphatidylserine-predicts-increased-bleeding-in-patients-with-severe-factor-viii-deficiency/. Accessed January 23, 2022.
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