Evaluation of plasma free hemoglobin levels in sickle cell anemia, hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria; use of LDH as a biomarker of hemolysis

• Grant number: 13/25138-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2014
• End date: July 31, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Camila Bononi de Almeida
• Grantee: Fernanda Camila Zauli Fabris
• Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Elevated Plasma Free Hemoglobin (PFHb) occurs in hemolytic anemia and is associated with a reduced half live of circulating erythrocytes. Sickle cell disease (SCD), hereditary spherocytosis (HS), and paroxysmal nocturnal hemoglobinuria (PNH) all share some complications caused by excess PFHb. SCD is characterized by a single mutation in the beta globin gene resulting in an anomalous hemoglobin (HbS), which polymerizes at low oxygen concentrations. Repetitive cycles of polymerization and depolymerization result in serious problems with oxygen transportation, disruption of erythrocytes, and release of hemoglobin to the plasma. Erythrocytes from HS present alterations in the membrane cytoskeleton, which leads these cells to a splenic trapping and hemolysis, contributing to the complications of the disease. In PNH, the production of the GPI enzyme is reduced due to a mutation in the PIG-A gene, resulting in fragile erythrocytes and platelets. The consequences are bone marrow failure, hemolytic anemia, and muscular and thrombosis problems. Currently there are few and inconclusive studies comparing hemolytic process in these diseases. Some researchers have hypothesized that the lactate dehydrogenase enzyme (LDH), which is present in major tissues and takes part in the glycolytic via, could represent a good marker of hemolysis. The aim of this study is compare the hemolytic processes present in SCD, HS and PNH by quantification and comparison of PFHb levels, reticulocytes numbers, and LDH, AST, ALT, bilirubin levels in these patients.