A 11 years old boy had a sudden onset left lower extremity swelling with pain and the symptoms gradually worsened. No symptoms of fever, headache, cough, chest tightness, chest pain, abdominal pain and diarrhea were reported. His CD4 + T lymphocyte cell count was 522 cells/µL and plasma VL was 943 copies/mL with a blood pressure around 97/69 mmHg at that time. He then initialed one-month topical treatment was ineffective and the symptoms aggravated until suddenly spread to the root of his thigh, accompanied by left lower extremity dyskinesia. The child was first tested positive with HIV at the age of two and was believed to be infected through mother-to-fetus transmission. He had been taken first-line regimen of ART (AZT + 3TC + NVP) since August 2014 with a CD4+ T lymphocyte cell count of 346 cells/µL at that time. The plasma HIV RNA was undetectable after half a year of ART.
His mother was HIV seropositive. The child had no personal or family history of thrombosis related disease. Nor surgery, trauma, prolonged bed rest, obesity, smoking and other deep vein thrombosis common risk factors were discovered.
On physical examination during hospital admission, the maximum circumference of his left thigh was 38 cm and the right thigh was 34 cm. The maximum circumference of his left calf was 27 cm and the right calf was 24 cm. His left lower extremity thigh was inflamed and swollen, accompanied by tenderness and varicose veins
Blood test indicated that his white blood cell (WBC) count was 3.28 × 109/L with a CD4+ T lymphocyte cell count of 430 cells/µL, hemoglobin (Hb) was 126 g/L and platelets was decreased to 66 × 109/L. His virology test suggested HIV RNA was 580 copies/mL. The coagulation function test showed PT was 14.0 seconds and activated partial thromboplastin time (APTT) was prolonged to 44.3 seconds. The international normalized ratio (INR) and Fibrinogen (FIB) were 1.16 and 15.1 mg/L respectively. D-dimer was 6.26 mg/L. C-Reactive Protein (CRP) was 32.14 mg/L, procalcitonin (PCT) was 0.029 ng/ml and erythrocyte sedimentation rate (ESR) was 41 mm/h. The aCLs IgG was at 57 (normal < 22), IgM was at 24 (normal < 10). Anti-neutrophil cytoplasmic antibody (pANCA) and anti-β2GPI antibody were tested positive. In addition, some other autoimmune antibodies were also tested positive: ANA (1:100, granular); dsDNA: +; nucleosome: ++; histone: +; mitochondrial M2: +. Other examinations including liver and kidney function were unremarkable.
Ultrasonography of lower vessels revealed deep venous thrombosis in his left lower extremity, accompanied by soft tissue edema and superficial lymphangiectasia. Vascular CT scan on left lower extremity showed extensive mural thrombosis (Figure).
He was diagnosed HIV comminated with thrombotic antiphospholipid syndrome. He was initially treated with low molecular weight heparin (LMWH) calcium 3000 IU every 12 hours for 6 weeks followed by warfarin (1.25 mg/day) for long-term anticoagulant therapy at a target INR of 2.0–3.0. Besides, methylprednisolone (40 mg/day) treatment was also given to the boy for ten days which was substituted with 30 mg/day prednisone after that. The prednisone dosage was gradually reduced by 5 mg each time every 2 weeks until reached 5 mg/d and maintained for another 2 months. Additionally, antiviral regiment was adjusted to ABC + 3TC + LPV/r due to his persistent high HIV viremia.
After one month of treatment, the swelling and pain gradually relieved and repeat vascular ultrasonography showed the blocked vessel was partial recanalized and platelets returned to normal. After 3 months of treatment, his symptoms continued to be ameliorated. However, the aCLs and β2-GP1 antibody titers were still tested positive. After 6 months of treatment, his left lower extremity blood vessels were returned to normal (Table 1).
Table 1
Basic information and Laboratory findings of the patient
Age(years) | 11 years old |
Sex | Male |
Personal and family histories | No |
January 2009 | Confirmed the diagnosis of HIV infection |
August 2014 | CD4 count: 346 cells/µL, and initial ART (AZT + 3TC + NVP) |
February 2015 | HIV RNA: undetectable |
January 2018 | CD4+ T count: 522 cells/µL, HIV RNA: 943 copies/mL |
February 2018 | CD4+ T count: 430cells/µL, HIV RNA:580 copies/mL |
Coagulation function test | PT: 14.0 s(normal, 11–16 s), APTT: 44.3 (normal, 23–40 s), INR: 1.16, FIB: 15.1 mg/L (normal, 2–4 mg/L), D-dimer: 6.26 mg/L (normal, 0–1 mg/L) |
Other laboratory findings | CRP: 32.14 mg/L (normal, 0–5 g/L), PCT: 0.029 ng/ml (normal, 0-0.046 ng/ml), ESR: 41 mm/h (normal, 0–15 mm/h), WBC: 3.28 × 109/L (normal, 3.5–9.5 × 109/L), Hb: 126 g/L (normal, 130–175 g/L), PLT: 66 × 109/L (normal, 125–350 × 109/L ACA (+), p-ANCA (+), β2-GP1-Ab (+), aCLs IgG (normal < 22) 57, IgM 24 (normal < 10) |
Symptoms | Left lower extremity swelling with pain |
Signs | left lower extremity thigh was inflamed and swollen, accompanied by tenderness and varicose veins, the maximum circumference of his left thigh was 38 cm and the right thigh was 34 cm. The maximum circumference of his left calf was 27 cm and the right calf was 24 cm. |
Prognosis | Thrombotic pediatric antiphospholipid syndrome (PAPS) |
Treatment | LMWH followed by warfarin; methyl prednisolone followed by prednisone, ABC + 3TC + LPV/r |
Evolution | Left lower extremity revascularized |