Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies.

GLEMBOTSKY AC; CONTRUFO G; RIVEROS D; HELLER PG; LEV PR; PIERDOMINICI MS; GARCIA A; MARTA RF; GOETTE NP; GRODZIELSKI M; ESPASANDIN YR; MOLINAS FC

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016 vol. 11

1932-6203

Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) areheterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrialmembrane potential (ÄØm), caspase 3 activation (aCasp3) and phosphatidylserine(PS) externalization in a cohort of adult ITP patients. Apoptosis was not related toplatelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization werenot increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms ofaCasp3. Incubation of normal platelets with ITP plasma induced loss of ÄØm, while PSexposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITPplatelets could be reproduced in normal platelets incubated with ITP plasma by adding normalCD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin Binhibitor- to this system protected platelets from apoptosis. Increased PS exposure wasalso observed when normal platelets and CD3+ lymphocytes were incubated with purifiedIgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies,pointing to the latter as responsible for platelet damage. Apoptosis was present in plateletsfrom all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent inthe patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated withplatelet count and decreased during treatment with a thrombopoietin receptor agonist.These results point to a key role for auto-antibodies in platelet apoptosis and suggest thatantibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon.