key: cord-010261-sy7esszi authors: Tenenbein, Milton; Israels, Sara J. title: Early coagulopathy in severe iron poisoning date: 2006-08-17 journal: J Pediatr DOI: 10.1016/s0022-3476(88)80381-0 sha: doc_id: 10261 cord_uid: sy7esszi nan pies, and Chonmaitree et al: found rhinoviruses in the middle ear fluid in three of 84 patients. According to Henderson et al., 2 acute otitis media is more closely associated with infections with RSV, adenovirus, and influenza virus than with infections with rhinovirus. Why the role of rhinoviruses in acute otitis media has not been shown earlier can be explained in several ways. The three studies 2.5,8 that have reported rhinovirus isolations in patients with otitis may have been made during a season when no major rhinovirus outbreaks occurred in the community. Henderson In addition to epidemiologic explanations, technical differences may explain some of the differences between the results of our study and earlier studies. The virus isolation samples were frozen at -70 ~ C within 2 hours after sampling. A blind passage was done of negative HeLa Ohio cell cultures, which increased the sensitivity of virus isolation. Furthermore, secretions were aspirated from the nasopharynx through the nostrils and a large amount of mucus was usually obtained, from which a swab was taken for virus isolation. We suggest that this collection method may have contributed to the relatively high frequency of rhinovirus infections detected. In addition to rhinovirus we found adenovirus and RSV in middle ear fluid, in agreement with our earlier studies 4 and with those of others) ,3,s The low rate of RSV isolation can be explained by the facts that the epidemic was only beginning at the end of the study and the direct detection of RSV antigen was not attempted) ,s-5 Virus as a sole pathogen was found in the middle ear fluid in seven (6%) patients who had received no antibiotic treatment. This observation is in agreement with the studies of Sarkkinen et al. 4 and Klein et al., 3 who found viruses as sole pathogens in 9% and 13%, respectively, of patients with acute otitis. We conclude that rhinovirus infection is associated with acute otitis media. In some patients rhinovirus may be the only pathogen detectable in middle ear fluid. occurs at least 24 hours after ingestion. Early gastrointestinal hemorrhage related to mucosal injury occurs within hours of overdose: Any coincident coagulopathy would aggravate the gastrointestinal hemorrhage. Our observations suppol:t the presence of an early, reversible coagulopathy dependent on the serum iron concentration in poisoned patients. The Journal of Pediatrics October 1988 (Table I) The four patients were allgirls, and only one survived. The overdose was accidental in the two toddlers and intentional in the teenagers. Coagulation factor analyses done at 24 to 90 hours after ingestion demonstrated markedly depressed activities of factors V, VII, IX, and X without associated thrombocytopenia. This pattern is typical of a hepatotoxic coagulopathy. At the same time, serum transaminase activities were grossly elevated (AST >1000 to 11,740 U/L), indicative of severe hepatocellular damage, whereas the serum iron concentrations were only mildly elevated (33 to 303 #g/dl) and less than the total iron binding capacity. Prothrombin time and activated partial thromboplastin time were also done within the first 24 hours in patients 1 and 2 (Table II) . These data demonstrated a significant early coagulopathy with grossly elevated serum iron concentrations and very modest hepatic dysfunction. Patient 1 had a subsequent improvement in hemostasis with a fall in serum iron concentration. Hepatotoxic coagulopathy was then documented at 28 and 24 hours, respectively, after the ingestion. All four patients had a severe hepatotoxic coagulopathy after 24 hours had elapsed. The depression of activities of factors V, VII, IX, and X is typical of this abnormality. The markedly elevated serum transaminase values and absence of thrombocytopenia support hepatic parenchymal damage rather than consumptive coagulopathy as the cause. Coagulopathy resulting from iron-induced hepatic damage is well known. Its onset is usually delayed for at least 24 hours after iron ingestion, making the early coagulation abnormalities in patients 1 and 2 noteworthy. Both PT and activated PTT were grossly prolonged during the time of markedly elevated serum iron concentrations and minimal transaminase elevation. The coagulation measurements in patient 1 also improved coincident with a precipitous fall in serum iron concentration and prior to the onset of the hepatic coagulopathy. These observations are supported by a single case of an iron-poisoned patient in whom abrupt onset of a coagulopathy occurred within hours of iron ingestion. 2 Coagulation studies were comparable to those in patients 1 and 2, and the abnormalities were resolving by the time evidence of hepatic dysfunction appeared. Thus there may be a biphasic coagulopathy in severe iron poisoning. The initial ~hase, occurring within hours of overdose, appears to be a functional, reversible, and serum iron concentration-dependent impairment of coagulation. The second, later phase is the well-known hepatotoxic coagulopathy of iron poisoning. Previous in viva studies in iron-poisoned rabbits 3 and dogs 4 have demonstrated a dose-related reversible dysfunction in coagulation of rapid onset, unrelated to shock or acidosis. Similar abnormalities have been demonstrated in in vitro studies in human plasma, 4a and the activated PTT prolongation was much greater than that of the PT, as in our patients 1 and 2. These effects were reversed after in vitro addition of a chelator to the test plasma. These data suggest a reversible interference with the function of Therapy for hemorrhage related to hepatotoxic coagulopathy involves coagulation factor replacement. If, however, there is functional impairment of coagulation factors because of peripheral inhibition by circulating free iron, it is unlikely the factor replacement or vitamin K would be beneficial. Thus therapy must include prompt removal of excess iron. Chelation therapy with deferoxamine is standard practice in severely iron-poisoned patients; unappreciated benefit may be the moderation of serious gastrointestinal hemorrhage. In many institutions rapid serum iron analysis is not available. This has led to the use of other factors (leukocytosis, hyperglycemia, vomiting, diarrhea, and radiographic demonstration of iron within the gastrointestinal tract) as indicators of theseverity of poisoning and the need for specific treatment. 6 If additional experience confirms the presence of an early coagulopathy in severe iron poisoning, the presence of early coagulation abnormalities could also suggest the need for deferoxamine therapy. The role of respiratory syncytial virus in otitis media in children A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion The role of respiratory syncytial virus and other viral pathogens in acute otitis media Identification of respiratory virus antigens in middle ear fluids of children with acute otitis media Presence of respiratory viruses in middle ear fluids and nasal wash specimens from children with acute otitis media Textbook of pediatric infectious diseases. Philadelphia: WB Saunders Isolation of rhinoviruses and coronaviruses from 38 colds in adults Virology of middle ear Clinical management of poisoning and drug overdose. Philadelphia: WB Saunders Acute iron intoxication with abruptly reduced levels of vitamin Kdependent coagulation factors Blood coagulation in acute iron intoxication The effects of iron on blood coagulation Blood coagulation and acute iron toxicity Acute iron poisoning Emergency assessment of severity in iron overdose by clinical and laboratory methods Marrow transplantation in chronic granulomatous disease: An update, with 6-year follow-up MD From the Division of Allergy/Immunology/Bone Marrow Transplantation, Children's Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia In 1984, we reported on the outcome of allogeneic bone marrow transplantation in an infant with chronic granulomatous disease. ~ This child has had low-level, stable, long-term mixed hematopoietic chimerism, and has been of Research Resources, National Institutes of Health. Submitted for publication March 30 We thank Ms. Merja Kleme, Ms. Maija Rautiainen, and Ms. Paula Vainio for technical assistance. His conditioning regimen before transplantation consisted of 2 mg/kg busulfan administered daily over 4 successive days, followed by cyclophosphamide, 50 mg/kg daily for 4 days. The