Background. Apolipoprotein-H (APOH), also known as b2-Glycoprotein I (b2GPI), is a plasma protein that was found in immune globulin product lots associated with thrombotic complications. Previously, APOH demonstrated anticoagulant activity, on the contrary, Lackner et al reported that APOH has procoagulant function. In the present study, we show that plasma derived APOH (pdAPOH) can be contaminated with activated coagulation factor XI (FXIa).

Methods. In-house modified simultaneous thrombin and fibrin generation assay (TGA) along with FXIa activity chromogenic assay (FXIa:C) were used to detect FXIa function. In parallel, high-performance liquid chromatography (HPLC) was used to demonstrate presence of FXIa in the procoagulant APOH.

Results. Functional FXIa activity was detected in plasma derived APOH (pdAPOH-FIT). This activity was comparable to that measured in purified FXIa and procoagulant immune globulin product (IGIV) batches known to contain FXIa. Anti-FXIa antibody blocked procoagulant activity of pdAPOH-FIT in the TGA. An APOH sample from another source pdAPOH-2 and recombinant APOH did not show any activity in the TGA. Presence of FXIa in pdAPOH-FIT was confirmed using the chromogenic assay. Using HPLC, we show that peaks for pdAPOH-FIT and pdAPOH-2 differed. However, procoagulant pdAPOH-FIT demonstrated peaks similar to pdAPOH-2 when spiked with FXIa.

Conclusions. APOH does not demonstrate procoagulant activity in TG assay in plasma. plasma derived APOH products may contain procoagulant FXIa contaminant in the amounts sufficient to impact TG which may be misinterpreted as procoagulant activity of APOH.

Disclosures

No relevant conflicts of interest to declare.

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2024
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