Reagents and methods for detecting pnh type ii white blood cells and their identification as risk factors for thrombotic disorders

Abstract

The disclosure relates to methods for detecting PNH Type II cell populations in biological samples as well as methods for determining whether a patient is at an increased risk for developing thrombocytopenia or thrombosis based on the percentage of PNH Type II cells in the patient's blood. The disclosure also features reagents and conjugates for use in the methods.

What is claimed is: 
     
         1 . A method for predicting whether a patient is at an increased risk for developing thrombosis, the method comprising:
 determining the percentage of paroxysmal nocturnal hemoglobinuria (PNH) Type II white blood cells of the total white blood cells of the same histological type in a biological sample from a patient; and   predicting whether the patient is at an increased risk for developing thrombosis, wherein the patient is at an increased risk for developing thrombosis if the percentage of PNH Type II white blood cells is greater than or equal to 1.2%.   
     
     
         2 . The method of  claim 1 , wherein the white blood cells are granulocytes or monocytes. 
     
     
         3 . The method of  claim 1 , wherein the biological sample is a whole blood sample. 
     
     
         4 . The method of  claim 1 , wherein a PNH Type II white blood cell population that is between 1.2% to 65.3%, inclusive of 1.2% and 65.3%, indicates that the patient is at an increased risk for thrombosis. 
     
     
         5 . The method of  claim 1 , wherein a PNH Type II white blood cell population that is greater than or equal to a) 5%, b) 10%, c) 20%, or d) 50% indicates that the patient is at an increased risk for thrombosis. 
     
     
         6 . The method of  claim 1 , further comprising monitoring the patient for the development of at least one symptom of thrombosis if the patient is at an increased risk of developing thrombosis. 
     
     
         7 . The method of  claim 1 , further comprising selecting an anti-thrombotic therapy for the patient if the patient is at an increased risk of developing thrombosis. 
     
     
         8 . The method of  claim 7 , wherein the anti-thrombotic therapy is an anticoagulant or thrombolytic agent. 
     
     
         9 . The method of  claim 8 , wherein the anticoagulant is coumadin, heparin, or derivatives thereof. 
     
     
         10 . The method of  claim 8 , wherein the thrombolytic agent is a tissue plasminogen activator, streptokinase, or a urokinase-type plasminogen activator. 
     
     
         11 . The method of  claim 1 , further comprising administering to the patient an anti-thrombotic therapy if the patient is at an increased risk for developing thrombosis. 
     
     
         12 . A method for selecting a therapy for a patient, the method comprising: selecting one or both of an anti-thrombotic therapy and an anti-thrombocytopenic therapy for a patient determined to have a paroxysmal nocturnal hemoglobinuria (PNH) Type II white blood cell population of greater than or equal to 1.2%. 
     
     
         13 . The method of  claim 12 , wherein the anti-thrombotic therapy is an anticoagulant or thrombolytic agent. 
     
     
         14 . The method  claim 12 , wherein the anti-thrombocytopenic therapy is a platelet transfusion 
     
     
         15 . The method of  claim 12 , wherein a non-lytic variant form of aerolysin protein is used to determine the percentage of PNH Type II white blood cells. 
     
     
         16 . A method for treating a patient, the method comprising administering to a patient in need thereof one or both of an anti-thrombotic therapy and an anti-thrombocytopenic therapy if the patient has a paroxysmal nocturnal hemoglobinuria (PNH) Type II white blood cell population of greater than 1.2%. 
     
     
         17 . The method of  claim 16 , wherein the anti-thrombotic therapy is an anticoagulant or thrombolytic agent. 
     
     
         18 . The method  claim 16 , wherein the anti-thrombocytopenic therapy is a platelet transfusion. 
     
     
         19 . The method of  claim 16 , wherein a non-lytic variant form of aerolysin protein is used to determine the percentage of PNH Type II white blood cells.