A 9-year-old boy had generally normal perinatal history, growth, and development. He presented with a fever, abdominal pain, and vomiting, all starting five days before admission. Diarrhea and hematochezia were not noted. On admission, his vital signs were body temperature 38.0 °C, blood pressure 98/44 mmHg, heart rate 82/min, and respiratory rate 16/min with an O2 saturation of 99%. Upper abdominal tenderness was found without abdominal swelling or hepatosplenomegaly. Complete blood count showed white blood cells 9540/µL, Hb 13.9 g/dL, and platelets 140 × 103/µL. Biochemical parameters showed total bilirubin 0.56 mg/dL, aspartate transaminase 58 IU/L, alanine transaminase 47 IU/L, urea nitrogen 6.3 mg/dL, creatinine 0.23 mg/dL, sodium 134 mEq/L, potassium 4.1 mEq/L, and C-reactive protein (CRP) 3.7 mg/dL. Routine analyses revealed mild thrombocytopenia, liver dysfunction, and elevated CRP. Coagulation studies revealed prolonged activated partial thromboplastin time (aPTT) of 92.4 sec, elevated D-dimer 3.7 µg/mL, LA positivity, and slightly low prothrombin activity 58% (reference range [RR] 75% – 135%) due to immunoglobin M (IgM) class anti-prothrombin antibody of 32.1 AU/mL (RR < 24.0 AU/mL). Immunoglobin G (IgG) class anti-phosphatidylserine/prothrombin antibody was also positive (> 50.0 units, RR < 2.0 units), which is associated with strong LA activity. The patient’s LA-positive plasma was examined using the thrombin generation test and clot waveform analyses (Fig. 1A, 1B, and 1C) as previously described . The clotting times in LA-positive plasma were significantly prolonged, compared to a healthy control.
A diagnosis of LAHPS was made. The patient tested positive for anti-nuclear antibody (ANA) titer 1:160, anti-double-stranded DNA (dsDNA) antibody of IgG 22 IU/mL, anticardiolipin antibody of IgG 16 U/mL, and anti-β2-glycoprotein I antibody of IgG > 50 units, but the patient did not fit the Systemic Lupus International Collaborating Clinics (SLICC) 2012 Classification Criteria . A contrast-enhanced computed tomogram revealed nodular lesions in the adrenal glands bilaterally (Fig. 1D and 1E). The diagnosis of acute adrenal failure due to adrenal hemorrhage was made on the basis of the clinical manifestations, mild hyponatremia (134 mEq/L), high plasma ACTH 1586 pg/mL (RR 7.2–63.3), low plasma cortisol 3.24 µg/dL (RR 6.2–18.0), blood glucose 37 mg/dL, low serum aldosterone 43.1 pg/mL, and relatively elevated plasma renin activity 9.1 ng/mL/hr. Hence, he received glucose (0.6 g/kg/dose), hydration (1700 mL/m2), and hydrocortisone (50 mg/m2/day). Hydrocortisone and fludrocortisone were continued for the adrenal replacement treatment at physiological doses. Repeated coagulation studies still showed positive LA and prolonged aPTT for 12 months (Fig. 2A).
At 10 years of age, he visited our hospital because of gait disturbances and weakness in all extremities after acute viral infection. He had butterfly rash, discoid rash, optic disc swelling, deranged renal function, and showed higher levels of ANA and anti-dsDNA antibody. Renal biopsy was performed, resulting in a diagnosis of lupus nephritis (Fig. 2B and 2C). His condition was diagnosed as SLE on the basis of the SLICC 2012 Classification Criteria . Intravenous pulsed treatments with methylprednisolone (30 mg/kg/day) and cyclophosphamide (500 mg/m2) were immediately initiated, followed by mycophenolate mofetil 400 mg/m2/day. The clinical signs were improved.