title: Phospholipase A2-induced coagulation abnormalities after bee sting.
abstract: We will examine the correlation between various bee venom phospholipase A2 (PLA2) concentrations and several parameters of coagulation in human plasma in order to offer a rationale for requesting a particular laboratory coagulation test after bee sting(s). We will also evaluate in vitro the influence of clinically available drugs with a noncompetitive inhibitory effect on PLA2 on the anticoagulant effect of bee venom PLA2. Prothrombin index (PTi), partial thromboplastin time (PTT), antithrombin III (AT III), soluble fibrin monomers (SFM), the activity of coagulation factors I, II, V, and VIII, and thrombelastography (TEG) parameters (split point [Sp], reaction time [R], kinetic time [K], coagulation time [R + K], maximal amplitude [MA], and the growth angle [alpha]) were determined before and after addition of 1.4, 2.7, and 4.1 units (1, 2, and 3 microg protein respectively) of bee venom PLA2. Linear regression was used to determine the significance of the relationship between these coagulation parameters and bee venom PLA2 concentrations used. To study the influence of ketamine, lidocaine, magnesium, furosemide, and cromolyn on the anticoagulant effect of bee venom PLA2, PTi and factor II- and V-activities were measured before and after addition of 2.7 units of PLA2 and PLA2 plus one of the tested substances. Determinations of F II, PTi, F V, and F VIII showed a negative correlation to bee venom PLA2 concentration (r = -0.88, -0.86, -0.81, and -0.79 respectively). A positive correlation was found for PTT (r = 0.69). FII- activity and PTi correlated better with bee venom PLA2 concentration than other parameters. F I, AT III, and SFM showed no changes. Whereas Sp, R, and K were prolonged by bee venom PLA2 and a was reduced, there was no correlation to the PLA2 concentration. Addition of none of the 5 substances could correct the effects of bee venom PLA2 on the coagulation. In a patient with toxic reaction or a severe anaphylactic reaction after bee sting(s) we suggest determinations of FII and/or PTi. This will allow a quick and economical assessment of coagulation abnormalities after bee sting(s). Noncompetitive PLA2-inhibitors (ketamine, lidocaine, magnesium, furosemide, and cromolyn) are unable to correct in vitro the anticoagulant effect of bee venom PLA2. They cannot be recommended at this stage for this purpose. Further investigations with competitive PLA2-inhibitors are warranted.
authors.affiliation: University of Heidelberg at Mannheim, Department of Pharmacology and Toxicology, Germany. petroia@rumms.uni-mannheim.de
authors.forename: G
authors.initials: G
authors.lastname: Petroianu
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: U
authors.initials: U
authors.lastname: Helfrich
authors.forename: W
authors.initials: W
authors.lastname: Maleck
authors.forename: R
authors.initials: R
authors.lastname: Rüfer
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001514:Bee Venoms / Q000737:chemistry / Q000201:enzymology*; D001516:Bees; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology*; D001780:Blood Coagulation Tests / Q000379:methods*; D004205:Cromolyn Sodium / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D007299:Insect Bites and Stings / Q000150:complications*; D007649:Ketamine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D016014:Linear Models; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010741:Phospholipases A / Q000009:adverse effects* / Q000032:analysis / Q000037:antagonists & inhibitors / Q000187:drug effects; D054467:Phospholipases A2; D011516:Prothrombin / Q000378:metabolism
chemical_list: D001514:Bee Venoms; D007649:Ketamine; D005665:Furosemide; D000990:Antithrombin III; D005165:Factor V; D011516:Prothrombin; D005169:Factor VIII; D005340:Fibrinogen; D008012:Lidocaine; D010741:Phospholipases A; D054467:Phospholipases A2; D008274:Magnesium; D004205:Cromolyn Sodium