In vitro evaluation of residual procoagulants in human intravenous immunoglobulins from 11 Chinese blood fractionation companies

Introduction: Residual procoagulants has been suggested to play an important role in the occurrence of thromboembolic events with intravenous immunoglobulin. Objective: This study investigated the predominant plasma proteases in 81 intravenous immunoglobulin lots from 11 Chinese manufacturers to examine the procoagulants of these human therapeutic intravenous immunoglobulin products. Methods: In one-stage clotting assays, the procoagulant activities of factors II, VII, IX, X, XI, and XII were quantified. Non-activated partial thromboplastin time and a modified thrombin generation test served as global and activated coagulation factor XI specific clotting assays, respectively. Results: The coagulation factor clotting activities of the 78 intravenous immunoglobulin lots were below the detection limit of the assays. The time to peak of thrombin generation using a thrombin generation test was longer than 35 min. The relevant amount of activated coagulation factor XI was below 0.37 nM. Non-activated partial thromboplastin time was greater than 203 s, except for the three pilot samples of manufacturer B in which we observed 0.48 to 0.09 IU/mL factor XI lever, 20 to 26 min for the time to peak of thrombin generation, 0.54 to 37.99 nM activated coagulation factor XI, and 155 to 182 s for non-activated partial thromboplastin time. Conclusions: The three intravenous immunoglobulin lots from manufacturer B showed significant procoagulant potential. Further study is required to determine whether a program for activated coagulation factor XI determination in intravenous immunoglobulin products should be launched in China. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.