Brown Recluse Spider Bite Mediated Hemolysis: Clinical Features, a Possible Role for Complement Inhibitor Therapy, and Reduced RBC Surface Glycophorin A as a Potential Biomarker of Venom Exposure

Abstract

BackgroundThe venom of Loxosceles reclusa (Brown Recluse spider) can cause a severe, life-threatening hemolysis in humans for which no therapy is currently available in the USA beyond supportive measures. Because this hemolysis is uncommon, relatively little is known about its clinical manifestation, diagnosis, or management. Here, we aimed to clarify the clinical details of envenomation, to determine the efficacy of the complement inhibitor eculizumab to prevent the hemolysis in vitro, and to investigate markers of exposure to Brown Recluse venom.Study Design and MethodsWe performed a 10-year chart review of cases of Brown Recluse spider bite-mediated hemolysis at our institution. We also designed an in vitro assay to test the efficacy of eculizumab to inhibit hemolysis of venom exposed red blood cells. Finally, we compared levels of CD55, CD59 and glycophorin A on venom exposed versus venom-naïve cells.ResultsMost victims of severe Brown Recluse spider mediated hemolysis at our institution are children and follow an unpredictable clinical course. Brown Recluse spider bite mediated hemolysis is reduced by 79.2% (SD=18.8%) by eculizumab in vitro. Erythrocyte glycophorin A, but not CD55 or CD59, is reduced after red blood cells are incubated with venom in vitro.ConclusionTaken together, our laboratory data and clinical observations indicate that L . reclusa venom exposure results in non-specific antibody and complement fixation on red blood cells, resulting in complement mediated hemolysis that is curtailed by the complement inhibitor eculizumab in vitro. Glycophorin A measurement by flow cytometry may help to identify victims of L . reclusa envenomation.

Therapeutic Plasma Exchange for Refractory Hemolysis After Brown Recluse Spider (Loxosceles reclusa) Envenomation

“…Hyalurodinase Fig. 1 Skin lesion on her knee with a central bulla and underlying purple discoloration prompts the spread of venom through subcutaneous tissue, and sphingomyelinase D is a cytotoxic enzyme thought to be responsible for complement-dependent hemolysis [6].…”

Bilateral optic neuropathy following bite from brown recluse spider (Loxosceles reclusa)

“…[8,9] Commonly reported manifestations are dermatologic, [10] hematologic, [11,12] nephrologic, [10] musculoskeletal [10] and neurologic [13]. Despite the research performed [14] and the Loxosceles- sensitive ELISA created [15], as of today the diagnosis remains clinical, based on history provided by the patient.…”

Eculizumab inhibits hemolysis in a model of ABO‐incompatible red blood cell transfusion

“…Cynthia R. Fata, MD 1 Eric A. Gehrie, MD 2 * Experimental conditions include six combinations from two RBC donors and three FFP donors. Percent hemolysis is reported as the mean of six experiments and the data are presented as mean (6SD).…”

“…1 RBCs were washed to remove additive solution and 5 mL RBCs were combined with 400 mL of thawed fresh-frozen plasma (FFP). We added 100 mg of eculizumab (Alexion Pharmaceuticals, Cheshire, CT) to the assay at various time points, ranging from the time of mixing incompatible RBCs and plasma to 24 hours after incubation began.…”