A 9-year-old previously healthy Syrian boy was admitted with a 1-day history of epistaxis, hematemesis, hematuria, and melena associated with periumbilical abdominal pain. He also has been complaining of pallor, decreased activity and appetite, and weight loss for a month prior to his presentation. A week before his admission, there was a noticeable increase in his pallor. Upon presentation, he was hypoactive, pale, and jaundiced. He was normothermic and hemodynamically stable. System examination revealed hepatosplenomegaly small palpable lymph node in the supraclavicular and inguinal region. The remainder of his physical examination was unremarkable.
His initial Laboratory tests at admission showed a picture of bi-cytopenia in the form of anemia and thrombocytopenia. Platelet 11 x 109/L (normal range: 150-400 x 109/L); hemoglobin 97 mg/L (normal range: 113-150 mg/J); white blood cells 10.2 x 109/L (normal range: 4-12 x 109/L); and reticulocyte counts 2.45% (normal range: 0.5%-1.5%). Peripheral blood smear showed red blood cell fragmentation (Schistocytes) at 1.45%, and white blood cells, mainly neutrophilia, displayed reactive changes in forms of toxic granulation.
Lactate dehydrogenase was 1,021 U/L (normal range: 125-220 U/L); aspartate aminotransferase 46 IU/L (normal range: 5-34 U/L); alkaline phosphatase 143 IU/L (normal range: 156-369 U/L); total bilirubin 41.3 micromol/L (normal range: ~20.5 micromol/L); and direct bilirubin 12.7 micromol/L (normal range: ~8.6 micromol/L). Blood urea nitrogen and creatinine were within normal limits. Urinalysis showed hematuria and hemoglobinuria. Coagulation screening tests were within the normal range; fibrinogen level was decreased to 1.72 g/L (normal range: 1.5-4.1 g/L); Coombs test was negative.
Initially, the patient was diagnosed with atypical idiopathic thrombocytopenic purpura (ITP) and treated with Intravenous Immunoglobulin (IVIG) 1 g/kg. He received two doses of IVIG without response, and his Hgb and platelet counts declined further.
In order to rule out bone marrow infiltration, bone marrow aspirations (BMA) and biopsy were performed. The preliminary report of the BMA did not suggest malignancy; however, it showed megakaryocytes which is suggestive of immune destruction. Therefore the patient was started on a six days trial of pulse steroid therapy (intravenous methylprednisolone 2 mg/kg/day divided twice a day), with no improvement in Hgb or platelet count. The final result of BMA revealed peripheral destruction of blood cells, indicating microangiopathic hemolytic anemia (MAHA), likely TTP, congenital or acquired due to an immune reaction to ADAMTS-13; this diagnosis was supported by repeated peripheral blood smear showing Schistocytes fragments of red blood cells >2.5% (Normal range <1.5%), accordingly a five days trial of fresh frozen plasma transfusion was initiated, in which the patient showed improvement in LDH and platelet levels.
In addition, bone marrow biopsy results showed morphologic evidence of frequent small epithelioid non-necrotizing granuloma. Considering that this is a nonspecific finding that could be attributed to various etiologies, including infections (viral, bacterial, and tuberculosis), infiltrating diseases such as sarcoidosis, and malignancies, further investigation has been pursued. Viral surveillance, including EBV, CMV, and HIV were negative. QuantiFERON-TB Gold was negative. Abdominal ultrasound and computerized chest and abdominal tomography (CT) scan showed splenomegaly with no significant lymph node enlargement. Since Brucella is endemic in Saudi Arabia and the patient had recently consumed a significant amount of unpasteurized goat milk and cheese, brucella titers were sent, and the result showed Brucella abortus 1:5,120 (normal range: <1:160), and Brucella melitensis 1:20,480 (normal range: <1:160).
A combination of Doxycycline (5 mg/kg/day orally twice a day) and Rifampin (20 mg/kg/day orally twice a day) antimicrobial therapy was commenced for a total of 6 weeks (42 days) to treat brucellosis. Once starting the anti-brucellosis management, the patient did not require further FFP transfusion. The ADAMTS-13 essay result showed: extremely low ADAMTS-13 activity, which was found at 0.02 IU/ml (normal range: 0.40-1.30 IU/ml), with an antigen assay below the detection level of 0.01 IU/ml (normal range: 0.41-1.41 IU/ml); and anti-ADAMTS-13 antibodies were detected at high concentrations of >95 IU/ml (>15 IU/ml is considered positive). All these findings, along with the presentation of thrombocytopenia and hemolysis, are specific to acquired TTP.
Several days following the commencement of antibiotic therapy, the platelets count and hemoglobin levels recovered to the normal range (Figure 1), while the lactate dehydrogenase levels decreased substantially to a normal level.