Age: 19.0
Sex: F
Vaccine: HEPA
Symptoms: Lymphoma, Lymphopenia, Mouth ulceration, Platelet count decreased, Skin ulcer
Clinical narrative: This 19 year old female subject was enrolled in blinded study for the prophylaxis of genital herpes disease. Medical history included oral ulcers with hemorrhage about one month prior to the time of reporting. The subject reportedly had no other significant medical history, reportedly had not taken any new medications (including over-the-counter medications or herbal medications), and denied any toxic exposures. The subject had no history of immunodeficiency virus infection, and was tested for HIV two years ago when she had a baby. The subject had no history of oral or genital sores. Concomitant medications included medroxyprogesterone acetate. On 5/10/04, the subject received the first IM injection of blinded study vaccine in the left deltoid. The subject had been randomized to the hepatitis A vaccine, inactivated arm of the study. On 6/1/04, approximately two weeks after vaccination, the subject reported a few weeks history of sores. She was evaluated by a dermatologist. The subject reported that there was one lesion on her gum which was slightly painful. The lesions were otherwise asymptomatic. The dermatologist found two shallow erosions with hemorrhagic puncta on the bilateral buccal mucosa along the bite line and approximately 3-mm hemorrhagic bulla on the upper gingival/hard palate border. The diagnosis was oral hemorrhagic bulla and shallow erosions; the differential diagnosis included hematoma and shallow erosions due to trauma. Treatment with topical fluocinonide 0.05% gel, twice daily, was prescribed. Herpes Simplex Virus culture was negative. The sores persisted, but the subject was otherwise well. The sores came and went. On 6/23/04, 44 days after the first dose of investigational product, the subject awoke with a nosebleed. The subject was unable to stop the nosebleed and presented to the emergency room where her nose was packed and she was discharged. The subject returned in the afternoon with persistent bleeding. The subject's nose was repacked, and she was sent home. Relevant laboratory results included a hematocrit of 21% and platelet count of 5,000 (units not specified). The police were called to locate the subject. She was hospitalized and transfused with packed red blood cells and platelets, and treated with IVIG and prednisone. The subject had received four to five units of PRBC. The subject was reported to be receiving platelets and blood ongoing. The subject was noted to have other abnormal laboratory results including an increased absolute reticulocyte count, decreased platelets, decreased hematocrit, decreased absolute lymphocyte count, increased segmented neutrophils count, increased megakaryocytes, increased serum lactate dehydrogenase, elevated vitamin B12, decreased transferrin saturation, and decreased iron. Additional abnormal laboratory results included low urate, decreased albumin, decreased calcium, increased reticulocyte percentage, decreased platelets, decreased hematocrit, decreased red blood cells, decreased lymphocyte count, increased red cell distribution width, decreased hemoglobin, increased total protein, increased glucose, decreased serum creatinine, decreased carbon dioxide, increased chloride, and decreased urinary nitrogen. The subject's platelet count remained very low (<3000); however, the nosebleed improved. The subject was reported to be stable (the nosebleed had stopped); however, the subject remained transfusion dependent (red blood cells and platelets) without a significant bump. Also, the subject's platelet count was 3,000 (units not specified) despite IVIG. Workup was ongoing, but based on bone marrow biopsy which showed increased megakaryocytes, the leading diagnosis was idiopathic thrombocytopenia. Possibilities also included lymphoma and human immunodeficiency virus (HIV) infection. The events were unresolved at time of reporting. The investigator considered there was reasonable possibility that the idiopathic thrombocytopenia and anemia may have been caused by investigational product. Follow up on 07/09/04 states: "Upon followup, it was noted that the oral sores were present continuously until she started prednisone, although the sores varied in intensity (came and went). Upon follow up, the peripheral smear read by the hematologist showed urinary nitrogen. The peripheral smear read by the hematologist showed an absence of platelets, but no red cell abnormalities. The hemolysis work up was essentially negative (only a absence of platelets, but no red cell abnormalities. In retrospect, the investigator thought that the oral lesions might have been related to thrombocytopenia. The investigator considered there was reasonable possibility that the idiopathic thrombocytopenia and anemia may have been caused by investigational product."