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

Abstract

Residual procoagulants has been suggested to play an important role in the occurrence of thromboembolic events with intravenous immunoglobulin. 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. 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. 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 35min. The relevant amount of activated coagulation factor XI was below 0.37 nM. Non-activated partial thromboplastin time was greater than 203s, except for the three pilot samples of manufacturer B in which we observed 0.48 to 0.09IU/mL factor XI lever, 20 to 26min for the time to peak of thrombin generation, 0.54 to 37.99 nM activated coagulation factor XI, and 155 to 182s for non-activated partial thromboplastin time. 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.