Serious Thrombocytopenia Due to Dengue Hemorrhagic Fever Treated with High Dosages of Immunoglobulin

Correspondence Figure 1. Recovery of platelet counts for 5 patients with dengue hemorrhagic fever treated with high doses of intravenously administered immunoglobulin (IVIG). Day 0, day IVIG therapy initiated. Sir—During the 2002 dengue hemor-rhagic fever (DHF) outbreak in Brazil, we treated 5 patients in Recife with DHF. The patients were white women aged 32, 37, 40, 41, and 67 years in whom DHF had been diagnosed on the basis of clinical and serological (ELISA with a positive IgM result) findings. All of them had positive tourniquet test results. Presence of extensive petechiae, epistaxis, and/or hematem-esis was evident. Findings of coagulation tests were normal except for accentuated thrombocytopenia (median platelet count, 20,000 platelets/mm 3 ; range, 18–36,000 platelets/mm 3), with no signs of disseminated intravascular coagulation. Bone marrow aspiration revealed normal or hyper-plastic megakaryocytes for all patients. Findings of thoracic and abdominal CT scans of all patients were normal. Other viral serological tests (for HIV, cyto-megalovirus, rubella virus, hepatitis B virus, and herpes C virus) and collagenosis tests (for antineutrophil cytoplasmatic anti-bodies, antinuclear antibodies, and anti– native DNA) had negative results. Two of our 5 patients underwent hemoconcen-tration. It should be noted that all patients had received volume replacement therapy before admission to our medical service, which may have affected their he-matocrit levels. All patients were admitted to our he-matology unit within 24–48 h after the first bleeding episode, where they received clinical care that included receipt of par-enteral hydration, acetaminophen, and third-generation g-globulin from Euro-pean donors, which had tested negative for any dengue antibody. The patients received 500 mg/kg per day of intravenously administered immunoglobulin (IVIG) in infusions of 3 h for 5 days. The evaluation of efficacy suggested immediate clinical response and recovery of the platelet level (figure 1 and table 1). Today there is good evidence that het-erologous secondary infection is the main risk factor for DHF, as explained by the immunologic enhancement hypothesis. According to this hypothesis, heterophilic antibodies complex with dengue viruses without neutralizing them, enhancing the efficiency of monuclear phagoctytes and exaggerating the immune reaction. Massive T-cell activation, with release of cy-tokines and induction of plasma leakage, is a major pathophysiological change that induces more-severe clinical symptoms and, in some cases, shock (dengue shock syndrome). Although the cause of throm-bocytopenia is not completely understood, recent studies suggest a role for the immune mediated destruction of platelets and vasculitis caused by immune complexes [1]. The mechanism …