Insight into the hypercoagulable state of high‐risk thrombotic APS patients: Contribution of aβ2GPI and aPS/PT antibodies

Objective Most high‐risk thrombotic antiphospholipid syndrome (APS) patients test positive for anti‐β2‐glycoprotein I (aβ2GPI) and anti‐phosphatidylserine/prothrombin (aPS/PT) antibodies. Information on the influence of these antibodies on thrombin generation and activated protein C resistance (aPCr) is still sparse and contradictory. Methods Plasma of 16 patients poured into a β2GPI affinity column allowed the perfect separation of aβ2GPI and aPS/PT antibodies. aPS/PT antibodies were further purified through a prothrombin affinity column. Obtained material was spiked into normal pooled plasma (NPP) and tested in the thrombin generation assay in the absence or presence of aPC. Results aPS/PT antibodies showed a marked anticoagulant effect. Affinity purified aPS/PT and aβ2GPI antibodies from five patients were compared. aPS/PT antibodies showed significantly prolonged lag time and time to peak (5.0 minutes [interquartile range (IQR)3.5–6.1] versus 2.7 minutes [IQR2.2–3.5], P = .03 and 8.7 minutes [IQR6.7–10.3] versus 5.7 minutes [IQR4.5–6.2], P  = .05, respectively) and significantly lower peak and velocity index (143 nmol/L [IQR131–163] versus 171 nmol/L [IQR157–182], P  = .03 and 35 nmol/L/min [IQR32–59] versus 72 nmol/L/min [IQR54–77], P  = .03, respectively). When aPC was added to the system, aPCr was significantly increased compared to controls for both aβ2GPI and aPS/PT antibodies. However, it was significantly stronger using aPS/PT antibodies. Median inhibition of endogenous thrombin potential was 22% (IQR16–33) with aPS/PT compared to 52% (IQR46–56) with aβ2GPI antibodies ( P  = .002). Conclusions Aβ2GPI antibodies show a mild anticoagulant and moderate procoagulant effect in thrombin generation and moderate aPC resistance. Conversely, aPS/PT antibodies show a strong anticoagulant effect and a strong aPCr.