Rev. Bras. Hematol. Hemoter. vol.36 número6

rev bras hematol hemoter. 2014;36(6):445–447

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

w w w . r b h h . o r g

Case

report

Accident

involving

a

2-year-old

child

and

Lonomia

obliqua

venom:

clinical

and

coagulation

abnormalities

Daniela

Nasu

Monteiro

Medeiros

,

Hélida

Conceic¸ão

Cavalcante

Torres

,

Eduarto

Juan

Troster

a_{HospitalIsraelitaAlbertEinstein,SãoPaulo,SP,Brazil}

b_{M ´BoiMirim,HospitalMunicipalDr.MoisésDeutsch,SãoPaulo,SP,Brazil}

c_{InstitutodaCrianc¸a,HospitaldasClínicas,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil}

a

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t

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Articlehistory:

Received25March2014 Accepted16July2014

Availableonline1October2014

Keywords: Child

Disseminatedintravascular coagulation

Accident

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b

s

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c

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Poisonsofcaterpillarshavedifferenteffectsoninflammatoryandcoagulationsystems. Thisisacasereportofa2-year-oldchildthataccidentallycameincontactwithseveral caterpillarsofthespeciesLonomiaobliqua.Atfirst,thepatient’sexamspresentedabnormal coagulationanddecreasedfibrinogen,butthepatientdidnotevolvetoactivebleedingor acuterenalfailure.Thepatientreceivedantilonomicserum15haftertheaccidentandthe treatmentwasrepeatedafteranother12hduetopersistentalterationsshownbythe coag-ulationexams.ThevenomofL.obliquahasseveralsubstancesthatactonthecoagulation andinflammatorysystems.Theeventischaracterizedbyahemorrhagicsyndromewith decreasesinfibrinogen.L.obliquaStuart-factoractivator(Losac)andL.obliquaprothrombin activatorprotease(Lopap)arecomponentsthatactwithprocoagulatoryeffects.The pro-inflammatoryactionoccursduetometalloproteases,hyaluronidasesandothersubstances withinflammatoryactivity.Studiesoncaterpillarvenomcangivenewperspectivesonthe treatmentofcancerandotherdiseasesthatcausedysfunctionoftheextra-cellularmatrix. ©2014Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.Published byElsevierEditoraLtda.Allrightsreserved.

Introduction

Caterpillars are the larval stage of butterflies and moths. Contactwiththebristlesofsomecaterpillarsinducevaried symptomsfrommilddiscomforttosystemicbleeding.1

Theearliest records ofaccidents involving lepidopteran caterpillarsinBrazilweredescribedbyZoroastroAlvarenga

∗ _{Correspondingauthorat:HospitalIsraelitaAlbertEinstein,Av.AlbertEinstein,627,Morumbi,05652-900SãoPaulo,SP,Brazil.} E-mailaddress:daninasu@gmail.com(D.N.M.Medeiros).

in1912,butitwasonlyin1967thatstudiesonthisinsectwere intensified.1 _{Between1989and2001,5673accidentsand 21} deathsoccurredinthesouthofBrazil.2

AccidentswithLonomiaobliqua(Figure1)occurmost fre-quentlyonthe upperlimbsofchildrenandrural workers.1 There isaseasonal distribution ofaccidentsinvolving this caterpillar, withincreased numbers ofcasesin spring and summer,theperiodthatcorrespondstothecaterpillarstage.1

http://dx.doi.org/10.1016/j.bjhh.2014.07.021

446

Figure1–Lonomiaobliqua.

L. obliqua releases toxins with anticoagulant properties throughitsbristles.Thesetoxinsincontactwiththeskincan causepain,redness,swellingandaburningsensationatthe site,andheadache,nausea,vomiting,hematoma,hematuria, bruising,anemiaandleucocitosis.2

The clotting time increases, coagulation factors levels decrease and fibrin degradation products increase after accidents with L. obliqua. The difference between L. obli-qua poisoning and other coagulopathies is the absence of thrombocytopenia.1

Case

report

ThisisthecaseofJNF,aCaucasianinfantboyof2yearsand2 months,bornandlivinginthecityofSãoPaulo,Brazil.

Thepatient was brought to the emergency department withahistoryofanaccidentinvolvingcontactwith caterpil-lars10hpreviously.Thepatienthadbeenonhisfather’slap inthegardenathomewhenhetouchedthetrunkofatree andfeltanintenseburningpaininthepalmofhishand.At thistime,thefathernoticedthatthechildhadtoucheda clus-terofcaterpillars.Thesecaterpillarsweredescribedasbeing moreorless5cminlengthandcoveredwithbristles,witha lightbrown/greencolor.Thepatienthadapastmedicalhistory ofrespiratoryatopyandregularlytookmontelukast,butwith nootherrelevantfamilymedicalhistory.Hewasina regu-larmedicalcondition,eupneic,hydrated,acyanotic,anicteric, afebrileandactive.Hisheartratewas67beatsperminute,the respiratoryratewas20breathsperminute,andbloodpressure 97×47mmHg.Hisweightwas14kg,height86cm,and oxy-gensaturationwas97%innormalatmosphere.Thephysical examinationwasnormal,exceptformicropapulesontheleft hand.Nohematomasorpetechiaewereevidenced.

Thepatientwasadmittedtotheintensivecareunit.The accidentwasratedasmoderatelyseverebecauseofthe alter-ations in clotting assays despite the lack of hemorrhagic manifestations.Fifteenhoursaftertheaccident,thepatient received three ampules of antilonomic serum. Before the infusions,hereceived10mg/kgofhydrocortisoneand1mg/kg ofdiphenidramin. Twelve hours after the first

administra-tionofantilonomicserum,hereceivedtwomoreampoules, becausethecoagulationtestswerestillabnormal.Thepatient evolvedwell,withoutbleeding,hematomaorhematuria,with goodurinaryexcretionandwithoutrenalalterations.Hewas dischargedwithnormallaboratoryexams(Table1).

Discussion

Thepatientdescribedinthisreportpresentedwithprolonged coagulationtimesincludingprothrombintimeandactivated partialthromboplastintimeaswell ashypofibrinogenemia, whichimprovedaftertheinfusionofantilonomicserum.He didnotpresentthrombocytopeniaduringhospitalization.

InaccidentsinvolvingL.obliquapoisoning,themostsevere manifestations are renal failure and intracerebral hemor-rhage;thispatientevolvedwithneitherofthesesigns.The pathophysiology of these alterations is poorly understood. Intracerebralhemorrhageisthemaincauseofdeath.3_Inthe stateofParanáinthesouthofBrazil,hemorrhagewaspresent in 50%ofthe patientssufferingaccidents involvingL. obli-qua.Hematuriaisfrequentlyobservedandsomehistological reportsshowacutetubularnecrosis.3

Thevenom ofL.obliquahasseveralsubstances thatact onthecoagulationandinflammatorysystems.Theeventis characterizedbyahemorrhagicsyndromewithadecreasein fibrinogen;decreasesinfibrinogenandthrombocytopeniaare severitymarkers.3

Inthecoagulationsystem,LosacandLopaphave procoag-ulatoryeffectswithLosacbeingdescribedfirst.Theenzyme activatesfactorXatlevelsthatdependontheconcentrationof venomandtheFXacomplexformedintegratesthe prothrom-binasecomplex.Bloodandkidneyvenomlevelsarehigh1h aftercontact,butthevenomiscompletelyeliminatedwithin 24h,suggestingthat theendotheliumand coagulation fac-torsarethevenom’smostlikelytargets.4_{Lopapisaprotease} withlinearkineticsthatactivatesprothrombinwithout form-ing theprothrombinasecomplex;its activityisinhibitedby theantilonomicserum.5,6

The pro-inflammatory actionoccurs due to metallopro-teases,hyaluronidasesandothersubstanceswith inflamma-toryactivity.7_{InjectingL.obliquavenominratsincreasedthe} expressionofendothelialE-selectin,andvascularcell adhe-sion protein1and caused theactivation of leukocyte,and the inductionofnecrosisfactorkappa-␤,cyclooxygenase-2, hemeoxygenase-1andinduciblenitricoxidesynthase.8_Lopap andLosacalsoplayaroleintheup-regulationofthe expres-sionofpro-inflammatorymoleculessuchasinterleukin8,and intercellularadhesionmolecule-1.4

Treatmentconsistsintheinjectionofantilonomicserum whichwasdevelopedinBrazilin1996byobtainingantibodies extractedfromhorsesimmunizedwithextractsfromthe bris-tlesofcaterpillars.ThisserumcontainstheF(ab’)fragmentof Gimmunoglobulin.9

revbrashematolhemoter.2014;36(6):445–447

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Table1–Laboratoryexams.

8hafteraccident 27hafteraccident 35hafteraccident Atdischarge

Prothrombintime(s) >120.0 160.0 16.3 12.3

INR 12.8 10.0 1.34 1.0

APTT(s) 123 37.9 27.0 27.0

APTTratio 3.71 1.32 0.9 0.9

Fibrinogen(mg/dL) – 35 87 115

Hemoglobin(g/dL) – 9.1 10.8 11.6

Hematocrit(%) – 28.0 32.4 35.5

Leukocytes(×103/uL) – 7.8 6.3 11.4

Platelets(×103/uL) – 237 264 352

Urea(mg/dL) – 15 17 28

Creatinine(mg/dL) – 0.3 0.3 0.3

Sodium(mEq/L) – 127 139 –

Potassium(mEq/L) 5.9 4.5 –

INR:internationalnormalizedratio;APTT:activatedpartialthromboplastintime.

Experimentalstudiesdidnotdemonstrateanormalizationof fibrinogenandclottingfactors1and6haftertheinfusionof EACA,respectively.3

Theunderstandingofthecomponentsandthe actionof thevenommaybeusefulintreatingdiseasesanddeveloping drugs.Lopapisrichinlipocalin,aproteininvolvedin cellu-larregenerationandremodelingandincontrolofapoptosis. Thestudy of this substance may help inthe treatment of diseasesinwhichthereisdysfunctionofthe extra-cellular matrix,suchasdiabetes,renal failure,and pulmonaryand heartdiseases.1,3 _{Lopapwasalsostudiedinratsinorderto} reversetheanticoagulanteffectoflowmolecularweight hep-arin.The outcome isinterestingas protamin,the antidote currentlyavailable,reversesonly60%oftheeffectcausedby lowmolecularweightheparin.8

Thisreport emphasizesthe importanceof knowingthe hemorrhagicand inflammatoryeffectsofL.obliquavenom, aswell as its treatment. Studying the substances involved enablesthedevelopmentofnewtreatmentsforcurrent dis-eases.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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