Inhibition of activated protein C and its cofactor protein S by antiphospholipid antibodies

Br J Haematol. 1990 Sep;76(1):101-7. doi: 10.1111/j.1365-2141.1990.tb07843.x.


We have investigated the effects of purified IgG fractions from plasma containing the lupus anticoagulant (LAC) and/or IgG anticardiolipin antibody (ACA) on the degradation of factor Va by an activated protein C-protein S complex. Plasma samples from 10 patients were studied. LAC was detected by a Russell's Viper venom technique. ACA was determined by ELISA. IgG fractions were obtained from each plasma sample by protein A-Sepharose fractionation. This fraction was shown to exhibit ACA/LAC activity. Using purified activated protein C (APC), protein S and phosphatidylserine/phosphatidylcholine, factor Va degradation was assessed in the presence and absence of IgG fractions from LAC/ACA containing plasmas. After 2 min incubation the mean factor Va degradation by APC and protein S in the presence of IgG LAC/ACA fractions was 14% compared with 52% with normal IgG. A similar effect was seen when phospholipid was substituted by washed freeze-thawed platelets. Experiments employing varying concentrations of protein S and phospholipid revealed marked differences in respect of the inhibitory specificity of the different antiphospholipid antibodies. These results indicate that antiphospholipid antibodies have an inhibitory effect on the activated protein C/protein S complex and provide some explanation for a relationship between antiphospholipid antibodies and thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / physiology*
  • Blood Coagulation Factors / analysis
  • Blood Coagulation Factors / immunology
  • Cardiolipins / immunology
  • Factor Va / metabolism
  • Female
  • Glycoproteins / antagonists & inhibitors*
  • Humans
  • Immunoglobulin G / physiology
  • Lupus Coagulation Inhibitor
  • Phospholipids / immunology*
  • Protein C / antagonists & inhibitors*
  • Protein S
  • Thrombosis / immunology*


  • Autoantibodies
  • Blood Coagulation Factors
  • Cardiolipins
  • Glycoproteins
  • Immunoglobulin G
  • Lupus Coagulation Inhibitor
  • Phospholipids
  • Protein C
  • Protein S
  • Factor Va