New data shows patients with Type II PNH cells experience platelet consumption and increased thrombosis risk

Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced presentation of data showing that the presence of Type II paroxysmal nocturnal hemoglobinuria (PNH) cells is correlated with thrombocytopenia, potentially indicating that patients with Type II cells experience ongoing platelet consumption and increased thrombosis risk. The study also highlights the need to identify Type II PNH cells from both red and white blood cells when diagnosing the disease and continues to demonstrate the need for high sensitivity flow cytometry methods.

The data were presented today at the 51st Annual Meeting of the American Society of Hematology in New Orleans in a poster session titled, “Identification and Clinical Significance of Type II Granulocytes Among Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Identified Using Multiparameter High-Sensitivity Flow Cytometry.”

In the study, a large population of patients was tested for the presence of PNH clones using a high-sensitivity flow cytometry assay, which identified a notable population of PNH patients with detectable PNH granulocyte (Gran) clones. In the evaluation of granulocyte markers for Type II clones by high sensitivity flow cytometry, the FLAER reagent identified all Type II granulocyte PNH clones while antibodies to GPI-linked proteins demonstrated less sensitivity.

“Detection of Type II granulocyte PNH cells is clinically important, as specific identification of PNH red blood cell clones can be confounded by transfusion or hemolysis,“ said Mayur K. Movalia, M.D., Associate Pathologist for Dahl-Chase Diagnostic Services and lead author of the study. “Further, the observed association of thrombocytopenia and Type II cells, without detectable differences in other peripheral blood cells or parameters, suggests that the presence of Type II cells may be an additional marker for increased thrombotic risk in patients with PNH.”

Thrombosis has been observed in PNH patients regardless of the level of hemolysis. Life-threatening thromboembolism is the most serious complication of PNH and accounts for 40 to 67 percent of patient deaths. (1)

“We appreciate the clinical importance of these study results showing a correlation between the presence of type II PNH cells and thrombocytopenia in patients with PNH,” said Stephen Squinto, Ph.D., Executive Vice President and Head of Research and Development at Alexion. “These data help advance our understanding of PNH and highlight the importance of using high sensitivity methods as well as evaluating Type II PNH cells in the diagnostic evaluation of potential PNH patients.”

Clinical Data

Researchers evaluated 2,921 consecutive patient blood samples submitted for PNH diagnostic testing to distinguish Type I, II and III granulocyte (Gran) clones. The samples were evaluated with a high-sensitivity flow cytometry assay for granulocytes including the FLAER reagent and complement inhibitor and lineage-specific antibodies. (2)

Following evaluation, 216 patient samples had a detectable PNH Gran clone, of which, clinical information was available for 162 of these patients. Of these samples, 19 patients demonstrated a distinct Type II Gran population (median Type II clone size = 7 percent). In 21 percent of the population, this Type II Gran clone represented >50 percent of the total (Type II + Type III) PNH cells.

Importantly, the presence of type II PNH granulocytes was associated with a significant increase in the incidence of thrombocytopenia. Patients with Type II Gran clones more commonly demonstrated platelet counts below 100,000 (68% vs. 44%,>9/L vs. 116x10⁹/L;>