Platelet factor 4 (PF4)/heparin antibody, typically associated with heparin therapy, is reported in some heparin-naive people. Seroprevalence in the general population, however, remains unclear. We prospectively evaluated PF4/heparin antibody in approximately 4,000 blood bank donors using a commercial enzyme-linked immunosorbent assay for initial and then repeated (confirmatory) testing. Antibody was detected initially in 249 (6.6%; 95% confidence interval [CI], 5.8%-7.4%) of 3,795 donors and repeatedly in 163 (4.3%; 95% CI, 3.7%-5.0%) of 3,789 evaluable donors. “Unconfirmed” positives were mostly (93%) low positives (optical density [OD] = 0.40-0.59). Of 163 repeatedly positive samples, 116 (71.2%) were low positives, and 124 (76.1%) exhibited heparin-dependent binding. Predominant isotypes of intermediate to high seropositive samples (OD >0.6) were IgG (20/39 [51%]), IgM (9/39 [23%]), and indeterminate (10/39 [26%]). The marked background seroprevalence of PF4/heparin antibody (4.3%-6.6%) with the preponderance of low (and frequently nonreproducible) positives in blood donors suggests the need for further assay calibration, categorization of antibody level, and studies evaluating clinical relevance of “naturally occurring” PF4/heparin antibodies.
Infection by Baylisascaris procyonis is an uncommon but devastating cause of eosinophilic meningitis. We report the fi rst case-patient, to our knowledge, who recovered from B. procyonis eosinophilic meningitis without any recognizable neurologic defi cits. The spectrum of illness for this organism may be wider than previously recognized. E osinophilic meningitis is defi ned by >10 eosinophils/ mm 3 in the cerebrospinal fl uid (CSF) or >10% eosinophils of the total CSF leukocyte count. In the United States, the most common cause of eosinophilic meningitis is the presence of a ventriculoperitoneal shunt, but worldwide it is infection by Angiostrongylus cantonensis (1). Other infectious causes of eosinophilic meningitis include Toxocara spp., Gnathostoma spinigerum, neurocysticercosis, and Baylisascaris procyonis. The latter is an intestinal roundworm endemic to the US raccoon population (2). B. procyonis has not been described in New Orleans but is known to occur in raccoons in northern Louisiana (D. Bowman, pers. comm.) and in the nearby states of Texas, Georgia, Oklahoma (2,3), and Mississippi (C. Panuska, unpub. data).Previously, all reported human cases of B. procyonis eosinophilic meningitis have resulted in death or severe neurologic sequelae. We describe a patient with clinically apparent B. procyonis eosinophilic meningitis, who appears to have completely recovered. This patient's recovery supports the notion that a wide spectrum of clinical disease exists for this parasite and that it may be a more common human infection than previously recognized. The CaseA 4-year-old boy from New Orleans, Louisiana, who had sickle cell disease and a history of a splenectomy, was admitted to our hospital with 1 day of headache, right arm pain, and emesis. He was alert and oriented; his oral temperature was 38°C; and physical examination found only mild upper extremity tremors, dysmetria, and bilateral extensor plantar response. His blood leukocyte count was 16,000/mm 3 , with 12% eosinophils; blood cultures yielded no growth. During the next 3 days, his headache and vomiting worsened and ataxia developed. Magnetic resonance imaging of the brain, performed on day 5 of illness, demonstrated cerebellar edema (Figure). CSF analysis showed the following: 5 erythrocytes, 1,734 leukocytes/mm 3 (55% of which were eosinophils), protein 290 mg/dL, and glucose 53 mg/dL. The boy was given 1 dose of mannitol (0.25 g/kg) and a loading dose of dexamethasone (1 mg/kg), followed by 0.25 mg/kg dexamethasone every 6 hours for 2 weeks. On day 9, a parasitic infection was suspected, and albendazole (10 mg/kg every 12 hours for 5 days) was begun. The boy's history was negative for travel outside the United States, raw food consumption, household pets, developmental disability, or pica. His mother reported household rodent infestation and fecal droppings on the patient's bed; raccoons had been seen in the neighborhood, but the boy had not been directly exposed to them. Three days after corticosteroid therapy began, headache and vomiting sto...
Significant numbers of workers (14%) chronically exposed to volatile organic chemicals commonly found in spray paints had elevated levels of uncharacterized antibodies to collagen IV, a basement membrane protein. No increased frequency of subjects with positive results for anti-glomerular basement membrane antibodies (anti-GBM) was found in this group. These anti-GBM antibodies are directed against a specific epitope on the non-collagenous domain (NC1) of the α3 chain of collagen IV. Anti-GBM antibodies are diagnostic for Goodpasture's syndrome that has been reported to occur following acute inhalation of volatile substances. In another group of workers, exposed both dermally and by inhalation to petroleum-based oil mists, 5% had positive results for antiGBM antibodies. We conclude that the measurement of general, uncharacterized antibodies to collagen IV may be a useful indicator of basement membrane damage in workers occupationally exposed to volatile organic chemicals.
IntroductionEosinophilic meningitis (EM) is a syndrome characterized by the presence of greater than 10 percent eosinophils in the cerebrospinal fluid. It is rare in the U.S. with outbreaks only in travelers returning from endemic areas and therefore remains a less recognized entity. However, this case demonstrates the importance of being aware of potential etiologies of EM.Case ReportThis is a 4 year old black male with a history of sickle cell disease presenting with headaches. This was treated as a pain crisis, but worsened with development of focal neurologic deficits. An evaluation included a MRI/MRA, showing cerebellar edema, and a lumbar puncture revealing 55 percent eosinophils. Serologies for Toxocara canis, Toxoplasma, lymphocytic choriomeningitic virus, and Mycoplasma were negative. There was no history of travel, exposure to undercooked snails/mollusks or neurosurgical procedures. However, there was an exposure to rat and raccoon feces; therefore, serologies for Angiostrongylus cantonensis and Baylisascaris procyonis were sent and positive for the latter. Treatment with steroids and albendazole resulted in improvement of the patient's symptoms and cerebrospinal fluid findings.DiscussionThe most common cause of EM in the pediatric population is ventriculoperitoneal shunts. Furthermore, parasitic etiologies should also be considered. First, Angiostrongylus cantonensis is a rat lung worm endemic to Southeast Asia and the Pacific Basin. Its larvae infect intermediate hosts like snails and mollusks through fecal contamination. Second, Baylisascaris procyonis is an ascarid parasite which is widely prevalent in raccoons and infects humans directly. After feco-oral contamination by humans, the larvae invade the meninges and die, eliciting a eosinophilic response. Furthermore, given the increasing peridomestication of raccoons, Baylisascaris procyonis poses a real threat to humans with potentially devastating sequelae. Clinical features include fever, headaches, visual disturbances, and neurologic deficits.ConclusionEM is a syndrome with multiple etiologies, including parasitic infections. Although rare, the worldwide prevelance of these organisms should have clinicians maintaining a high index of suspicion.
Heparin-Induced Thrombocytopenia (HIT) is classically viewed as a drug-induced immune disorder triggered by exposure to the anticoagulant drug, heparin. However, HIT may also be considered a dysregulated autoimmune response to two naturally occurring substances, Platelet Factor 4 (PF4), a platelet protein, and heparin, a tissuederived glycosaminoglycan. Until recently, studies of HIT and PF4/heparin antibody seroconversion have been exclusively focused on patients exposed to heparin or heparinlike drugs, including low-molecular weight heparin, the heparinoids and the synthetic agent, fondaparinux. Recent reports, however, indicate that PF4/heparin antibodies may arise spontaneously in some individuals in the absence of heparin (Warkentin Am J Med 2008; Hursting J Thromb Thrombolysis, 2008). We undertook this study to document the seroprevalance of “naturally-occurring” PF4/heparin antibodies in healthy subjects without prior heparin exposure. To study “healthy” subjects, we used blood bank donors as a surrogate population. Samples from blood bank units were obtained through Duke Transfusion services/American Red Cross (ARC). Donors met eligibility criteria for blood donation to the ARC and generally, represent a healthy population (http://www.redcross.org/services/biomed/0,1082,0_557_,00.html#hem). A Duke IRB waiver was issued due to use of anonymous samples. Plasma from donor units/segments were assayed in duplicate for the presence of PF4/heparin antibodies using a commercially available PF4/heparin ELISA (PF4 enhanced IgG,A,M kits, Genetics Technology Institute, Waukesha, WY). Positivity was defined by the manufacturer as A405nm ≥0.4. Positive samples were stratified into low, (A405nm=0.4–0.6), intermediate (A405nm=0.61–0.99) or high-positive values (A405nm≥1.0). High and intermediate positive samples were further isotyped using IgG and IgM specific antibodies (Sigma, St. Louis, MO). Of the 970 blood bank donors tested to date, 31 samples (3.2%) were positive using the manufacturer’s cut-off value. Repeat testing confirmed positivity in all 31 samples. Of those testing positive, 26 were low-positive (2.3% of overall cohort; 84% of all positive samples), 1 sample was intermediate positive (0.1% of overall cohort; 3.2% of positive samples) and 5 samples were high-positive (0.5% overall cohort; 16% of positive samples). Isotyping of 6 high/intermediate positive samples revealed IgG in 3 patients, IgM in the remainder. There was no correlation between antibody positivity and ABO blood type. In summary, our data reveals a high prevalence of PF4/heparin antibodies, the majority of which are low-positive values (~84%). Many of these low-positive samples likely reflect background “noise” of the assay and could be eliminated using a higher cut-off for positivity. We also found a seroprevalance of 0.5% of high positive antibodies, of IgG and IgM isotype, supporting the notion that some individuals may have “naturally-occuring”
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