C4B and hyperinsulinemic hypoglycemia, familial, 4: R. R. Forastiero studied the pathophysiology behind deficient protein S in patients with APS in 1996 and found that patients with APS who were anticardiolipin positive were found to develop acquired protein S and C4b‐BP deficiency, and those who were lupus anticoagulant positive and anticardiolipin antibody negative were found to develop free protein S deficiency, probably due to the abnormal binding site of free protein S to the C4b‐BP [13].