Thrombin generation analysis in a paroxysmal nocturnal haemoglobinuria (PNH) clone population

• Grant number: 10/19431-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Elbio Antonio D'Amico
• Grantee: Elbio Antonio D'Amico
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Audrey Kruse Zeinad Valim

Abstract

PNH is a rare haematopoietic stem cell disorder characterized by acquired hemolytic anemia, intermittent haemoglobinuria, bone marrow failure and thromboembolic events. The pathophysiology is related to glycosyl phosphatydilinositol (GPI) anchor deficiency, that supports the inactivation of the complement system at the cellular surface. Thromboembolic phenomena (with mechanism not well defined yet) develop in 40% of patients, with 40 to 67% mortality. Due to raised incidence of such phenomena and high taxes of mortality, the primary antithrombotic prophylaxis is indicated in patients that have large clones (percentage of cells with GPI anchor deficiency above 50%) and platelet count more than 100.000/mm³. However, the PNH syndrome is closely related to bone marrow aplasia (AA). This link is recognized since 1961, and the finding of thrombocytopenia in such individuals is not uncommon. However, there are no data related to the thrombotic risk in thrombocytopenic individuals, even in those that have large clones. The objective of this project is to evaluate the thrombotic risk in patients with PNH clone through thrombin generation method (CAT - Calibrated Automated Thrombogram®, Thrombinoscope B.V., Maastricht, the Netherlands), and evaluate the platelet role in thrombin generation. The identification of a thrombotic risk marker (thrombin generation) in this subgroup of individuals might be useful in the therapeutic decision of antithrombotic prophylaxis. (AU)