Close link between antiphosphatidylserine/prothrombin antibodies, lupus anticoagulant, and activated protein C resistance in tetra antiphospholipid antibody-positive subjects

J Thromb Haemost. 2023 Nov;21(11):3138-3144. doi: 10.1016/j.jtha.2023.06.033. Epub 2023 Jul 7.

Abstract

Background: Most of the carriers/patients triple-positive for antiphospholipid antibodies (lupus anticoagulant [LAC], immunoglobulin G [IgG]/immunoglobulin M [IgM] anticardiolipin, and anti-β2-glycoprotein I antibodies) are tetra-positive, being positive for antiphosphatidylserine/prothrombin (aPS/PT) antibodies. The relationship between aPS/PT titer, LAC potency, and resistance to activated protein C (aPC-R) has not been investigated.

Objectives: The aim of this study was to clarify the mutual interdependence of these parameters in tetra-positive subjects.

Methods: Twenty-three carriers and 30 patients with antiphospholipid syndrome, none of whom were being treated with anticoagulants, and 30 age- and sex-matched controls were studied. Detection of aPS/PT, LAC, and aPC-R in each individual was performed with established methods in our laboratory. Carriers and patients were positive for IgG or IgM aPS/PT or for both isotypes without significant difference. Since both IgG and IgM aPS/PT have anticoagulant activity, we used the sum of their titers (total aPS/PT) for the correlation studies.

Results: Total aPS/PT in all individuals studied exceeded that in controls. There was no difference in total aPS/PT titers (P = .72), LAC potency (P = .56), and aPC-R (P = .82) between antiphospholipid antibody-carriers and patients with antiphospholipid syndrome. There was a significant correlation between total aPS/PT and LAC potency (r = 0.78; P < .0001) and between total aPS/PT titers and aPC-R (r = 0.80; P < .0001). LAC potency also was correlated significantly with aPC-R (r = 0.72; P < .0001).

Conclusion: This study shows that there is interdependence between aPS/PT, LAC potency, and aPC-R.

Trial registration: ClinicalTrials.gov NCT02157272.

Keywords: antiphospholipid syndrome; lupus coagulation inhibitor; protein C; prothrombin; β2-glycoprotein I.

MeSH terms

  • Activated Protein C Resistance*
  • Antibodies, Antiphospholipid
  • Antiphospholipid Syndrome* / diagnosis
  • Humans
  • Immunoglobulin G
  • Immunoglobulin M
  • Lupus Coagulation Inhibitor
  • Phosphatidylserines
  • Prothrombin

Substances

  • Lupus Coagulation Inhibitor
  • Prothrombin
  • Phosphatidylserines
  • Antibodies, Antiphospholipid
  • Immunoglobulin G
  • Immunoglobulin M

Associated data

  • ClinicalTrials.gov/NCT02157272