Occupational Occupational H t lH t lHematologyHematology

Presented by: Presented by: Naseri_aNaseri_a; MD; MDOccupational Medicine SpecialistOccupational Medicine Specialistp pp p

Exposure to hematotoxin may causeExposure to hematotoxin may causeExposure to hematotoxin may causeExposure to hematotoxin may cause

Blood cell survivalBlood cell survival(( DenaturationDenaturation HB &HB & Blood cell survivalBlood cell survival( ( DenaturationDenaturation HB & HB & HemolysisHemolysis))MetabolismMetabolism((PorphyriaPorphyria)) MetabolismMetabolism((PorphyriaPorphyria))

FormationFormation((AplasiaAplasia)) Morphology and Function Morphology and Function ((PreleukemiaPreleukemia& &

leukemia)leukemia) CoagulationCoagulation(Thrombocytopenia)(Thrombocytopenia)

Disorders Associated With Disorders Associated With Shortened Red Blood Cell SurvivalShortened Red Blood Cell Survival

MethemoglobinemiaMethemoglobinemia and and HemolysisHemolysis Produced Produced By Oxidant ChemicalBy Oxidant Chemical

HemolysisHemolysis Associated With Exposure To Associated With Exposure To Heavy MetalsHeavy MetalsHeavy MetalsHeavy Metals

ThTh P h iP h i The The PorphyriasPorphyrias

Disorders Associated With Disorders Associated With Decreased Oxygen SaturationDecreased Oxygen Saturation

Carbon monoxide poisoningCarbon monoxide poisoning

Disorders Affecting Blood Cell Disorders Affecting Blood Cell Formation & MorphologyFormation & Morphology

AplasticAplastic anemia : anemia : BenzeneBenzene, , Ionizing RadiationIonizing Radiation

MyelodysplasticMyelodysplastic Syndromes (MDS)Syndromes (MDS)

Multiple Myeloma (MM)Multiple Myeloma (MM)p y ( )p y ( )

Toxic ThrombocytopeniaToxic Thrombocytopenia Toxic ThrombocytopeniaToxic Thrombocytopenia

Methemoglobinemia and Hemolysis Produced Methemoglobinemia and Hemolysis Produced B O id Ch i lB O id Ch i lBy Oxidant ChemicalBy Oxidant Chemical

MethemoglobinMethemoglobin is formed by oxidation of ferrous is formed by oxidation of ferrous HbHb (Fe 2+) to (Fe 2+) to gg yy ( )( )ferric ferric HbHb (Fe 3+) (incapable of delivering oxygen to the tissues)(Fe 3+) (incapable of delivering oxygen to the tissues)

Blue WorkersBlue Workers Blue WorkersBlue Workers

Chemicals associated withChemicals associated withmethemoglobinemia or oxidative hemolysismethemoglobinemia or oxidative hemolysis

ChmicalChmical UseUseAnilineAniline

Rubber,dyestuffs,production ofRubber,dyestuffs,production of MBIMBI

NitroanilineNitroaniline DyesDyes

ToluidineToluidine Dyes,organic chemicalsDyes,organic chemicals

PP--ChloranilineChloraniline Dyes,pharmaceuticals,pesticidesDyes,pharmaceuticals,pesticides

OO ToluidineToluidine Laboratory analytic reagent production of trypan blueLaboratory analytic reagent production of trypan blueOO--ToluidineToluidine Laboratory analytic reagent,production of trypan blue Laboratory analytic reagent,production of trypan blue stain,chlorine test kits,test tapesstain,chlorine test kits,test tapes

NaohthaleneNaohthalene Fumigants used in clothing industryFumigants used in clothing industryParadichlorobenzeneParadichlorobenzene Fumigants used in clothing industryFumigants used in clothing industryParadichlorobenzeneParadichlorobenzene Fumigants used in clothing industryFumigants used in clothing industry

NitratesNitrates Soil fertilizersSoil fertilizers

TrinitrotolueneTrinitrotoluene ExplosivesExplosives

Pathophysiology of Oxidant Pathophysiology of Oxidant HemolysisHemolysis

OxidationOxidation HbHb DenaturationDenaturation HbHb Oxidation Oxidation HbHb Denaturation Denaturation HbHbPrecipitated HB within RBC Alter the Precipitated HB within RBC Alter the surface membrane of RBC and increasedsurface membrane of RBC and increasedsurface membrane of RBC and increased surface membrane of RBC and increased rigidity and leakage rigidity and leakage ExtravascularExtravascularcompartment Bite cell or blister cellcompartment Bite cell or blister cellcompartment Bite cell or blister cellcompartment Bite cell or blister cell

AnilineAnilineAnilineAniline AnilineAniline use:use:

DyesDyes Rubber industryRubber industry

Aniline properties:Aniline properties:FF l bl d dil h ki h h hl bl d dil h ki h h h FatFat--soluble and readily penetrate the skin, even the through soluble and readily penetrate the skin, even the through clothing clothing

Vapor form may entry to the body through the lungVapor form may entry to the body through the lungp y y y g gp y y y g g

Clinical presentationClinical presentationClinical presentationClinical presentation

MildMild: asymptomatic blueness of lips & bed nails: asymptomatic blueness of lips & bed nails

ModerateModerate: fatigue, tachycardia, headache, exercise : fatigue, tachycardia, headache, exercise intolerance, intolerance, dyspneadyspnea

SevereSevere: : Altered consciousness, Coma, deathAltered consciousness, Coma, death

Clinical presentationClinical presentationClinical presentationClinical presentation

%Methemoglobinemia SymptomsSymptoms1010--3030 Cyanosis, mild fatigue, Cyanosis, mild fatigue,

tachycardiatachycardia3030--5050 Weakness, breathlessnessWeakness, breathlessness

Headache, exercise Headache, exercise intoleranceintolerance

5050--7070 Altered consciousnessAltered consciousness

>70>70--8080 Coma deathComa death>70>70 8080 Coma, deathComa, death

Para clinic findingPara clinic findingPara clinic findingPara clinic finding

Freshly drawn blood appear dark maroonFreshly drawn blood appear dark maroon--brown and brown and does not become red after exposure to airdoes not become red after exposure to air

Pulse Pulse oximetryoximetry: normal: normal

ABG: Normal oxygen tension ABG: Normal oxygen tension

CoCo--oximetryoximetry

Para clinic findingPara clinic findingPara clinic findingPara clinic finding

CBC: CBC: Anemia, Anemia, reticretic

PBS:PBS: PBS:PBS: Bite or blistered red cell (Bite or blistered red cell (heinzheinz body) body) ReticulocytosisReticulocytosis ((Polychromasia,possiblyPolychromasia,possiblyyy (( y ,p yy ,p y

nucleated red cells)nucleated red cells)

PreventionPreventionPreventionPrevention Minimize atmospheric and Minimize atmospheric and cutaneouscutaneous exposure to oxidizing exposure to oxidizing pp p gp g

chemicals such aschemicals such as coal tarcoal tar

Biologic monitoring in the workplace by measuring Biologic monitoring in the workplace by measuring methemoglobinmethemoglobin levels and levels and reticulocytereticulocyte countscounts

Screening for G6PD deficiency before a hemolytic episode or Screening for G6PD deficiency before a hemolytic episode or 11--2 month after the2 month after the hemolysishemolysis11 2 month after the 2 month after the hemolysishemolysis

TreatmentTreatmentTreatmentTreatment Removal of the offending agents & DecontaminationRemoval of the offending agents & Decontaminationg gg g

Mild intoxication ( <%20) observation Mild intoxication ( <%20) observation

Moderate to severe (>%30) Moderate to severe (>%30) oxygen%100oxygen%100, , methylenemethyleneblueblueblue blue solution %1 at a dose of 1solution %1 at a dose of 1--2 mg/kg over 10 minutes 2 mg/kg over 10 minutes

Exchange transfusion Exchange transfusion

Hemolysis Associated With Exposure To Hemolysis Associated With Exposure To Heavy MetalsHeavy Metals

ArsineArsine ArsineArsine LeadLead MercuryMercury MercuryMercury CopperCopper

A tiA ti AntimonyAntimony Mechanism of Mechanism of hemolysishemolysis is is unknown,butunknown,but it is thought it is thought

to be related to the affinity of this directlyto be related to the affinity of this directly cytolyticcytolyticto be related to the affinity of this directly to be related to the affinity of this directly cytolyticcytolyticmetals to metals to thiolthiol groups groups such as are found on the such as are found on the surfaces of RBCsurfaces of RBC

ArsineArsineArsineArsine colorless, non irritating gascolorless, non irritating gas, g g, g g

Produced by the action of acid on a metal contaminated with Produced by the action of acid on a metal contaminated with arsenic: arsenic: Smelting & refinery Smelting & refinery

P ti f d ti d i i th i d tP ti f d ti d i i th i d t Preparation of conducting devices in the semiconductor Preparation of conducting devices in the semiconductor industryindustry

Respiratory tract is the most important portal of entryRespiratory tract is the most important portal of entry

Clinical PresentationClinical PresentationClinical PresentationClinical Presentation Acute arsine poisoning :Acute arsine poisoning :

22--24 h after exposure: acute and massive IV 24 h after exposure: acute and massive IV hemolysishemolysis

Nausea, vomiting, abdominal cramping, headache, malaise Nausea, vomiting, abdominal cramping, headache, malaise and and dyspneadyspnea

TeaTea--colored urinecolored urine

Ph/ExamPh/ExamPh/ExamPh/Exam

garlicky odor , fever tachycardia, garlicky odor , fever tachycardia, tachypneatachypneaand hypotensionand hypotensionand hypotensionand hypotension

JaundiceJaundice generalized nonspecific abdominalgeneralized nonspecific abdominal JaundiceJaundice, generalized nonspecific abdominal , generalized nonspecific abdominal tendernesstenderness

Laboratory FindingsLaboratory FindingsLaboratory FindingsLaboratory Findings HemoglobinuriaHemoglobinuriagg

Decreased plasma Decreased plasma haptoglobinhaptoglobin & increased free & increased free HbHbpp p gp glevelslevels

The plasma may be brownishThe plasma may be brownish--red from the presence red from the presence of of methemalbuminemethemalbumine

PBS: PBS: PoikilocytosisPoikilocytosis, basophilic stippling and , basophilic stippling and polychromasiapolychromasiapolychromasiapolychromasia

Laboratory FindingsLaboratory FindingsLaboratory FindingsLaboratory Findings

Increased total & indirectIncreased total & indirect bilirubinbilirubin Increased total & indirect Increased total & indirect bilirubinbilirubin DIC DIC

low fibrinogen levellow fibrinogen level low fibrinogen level low fibrinogen level prolonged PTprolonged PT schistocyteschistocyte thrombocytopeniathrombocytopenia

Altered renal function increased serum CrAltered renal function increased serum Cr Precipitated hemoglobin castsPrecipitated hemoglobin casts Direct toxicity of arsine on renal tubular cellsDirect toxicity of arsine on renal tubular cells

TreatmentTreatmentTreatmentTreatment

Vigorous hydration Vigorous hydration h f i if lh f i if l bb Exchange transfusion if plasma Exchange transfusion if plasma HbHb

levels>400levels>400--500mg/dl500mg/dl HemodialysisHemodialysis if ARF developedif ARF developed All survivors of acute arsine poisoning must be All survivors of acute arsine poisoning must be p gp g

evaluated for evaluated for at least 1 yearsat least 1 years

LeadLeadLeadLead

Suppression Suppression erythropoiesiserythropoiesis and and hemeheme synthesis synthesis

Hemolytic anemiaHemolytic anemia

PorphyriaPorphyria

Toxic substances associated with Toxic substances associated with acquired porphyria in human acquired porphyria in human

ToxinToxin UseUseToxinToxin UseUseHexachlorobenzeneHexachlorobenzene FungicideFungicide2 4Dichlorophenol2 4Dichlorophenol HerbicideHerbicide2,4Dichlorophenol2,4Dichlorophenol HerbicideHerbicide2,4,5Trichlorophenol2,4,5Trichlorophenol HerbicideHerbicide2 3 7 8Tetrachlorodibenzo2 3 7 8Tetrachlorodibenzo--pp--dioxindioxin Herbicide contaminantHerbicide contaminant2,3,7,8Tetrachlorodibenzo2,3,7,8Tetrachlorodibenzo pp dioxindioxin Herbicide contaminantHerbicide contaminantOO--BenzylBenzyl--pp--chlorophenolchlorophenol Cleanser and disinfectantCleanser and disinfectant22--BenzylBenzyl--pp--dichlorophenoldichlorophenol CommercialCommercial disinfectantdisinfectantyy pp pp CommercialCommercial disinfectantdisinfectant

Vinyl chlorideVinyl chloride PlasticsPlasticsLeadLead Paint compoundsPaint compoundsLeadLead Paint compoundsPaint compoundsAluminumAluminum Phosphorus binderPhosphorus binder

AplasticAplastic AnemiaAnemiaAplasticAplastic AnemiaAnemia

Idiopathic & secondaryIdiopathic & secondary DrugsDrugs Idiopathic & secondary Idiopathic & secondary DrugsDrugsChemicalsChemicalsRadiationRadiationInfectionInfectionImmunologicImmunologic

Drugs(Drugs(chloramphenicol,acetazolamide,phenylbutazonechloramphenicol,acetazolamide,phenylbutazone, , phenytoin,sulfonamidephenytoin,sulfonamide,….,….

Benzene, Ionizing Radiation & Benzene, Ionizing Radiation & cytotoxiccytotoxic drugs such drugs such as anti metabolites and as anti metabolites and alkylatingalkylating agents agents y gy g gg

BenzeneBenzeneBenzeneBenzene

Workers at greatest risk of exposure:Workers at greatest risk of exposure: RubberRubber Workers at greatest risk of exposure: Workers at greatest risk of exposure: RubberRubbermanufacturingmanufacturing, , shoemakingshoemaking, , petroleumpetroleum

BM BM HypocellularityHypocellularity with fattywith fatty replacementreplacementyp yyp y yy pp Prognosis:Prognosis:

Up to 40% patient may recover completely after removal of Up to 40% patient may recover completely after removal of exposureexposure

Treatment :Treatment :supportive (transfusion, EGF,GCSF,GMCSF),supportive (transfusion, EGF,GCSF,GMCSF),AndrogensAndrogens AllogenicAllogenic BMBM trasplantationtrasplantation))Androgens, Androgens, AllogenicAllogenic BM BM trasplantationtrasplantation))

Other causes of aplastic anaemiaOther causes of aplastic anaemiaOther causes of aplastic anaemia Other causes of aplastic anaemia

Trinitrotoluene which is absorbed readilyTrinitrotoluene which is absorbed readily Trinitrotoluene, which is absorbed readily Trinitrotoluene, which is absorbed readily through the skin, has been associated with through the skin, has been associated with aplastic anaemia in munition plantsaplastic anaemia in munition plantsaplastic anaemia in munition plants aplastic anaemia in munition plants

Pesticide lindane (gammaPesticide lindane (gamma--benzene benzene hexachloride )hexachloride )hexachloride )hexachloride )

Ethylene glycol ethersEthylene glycol ethers Arsenic Arsenic

Hematologic cancer:Hematologic cancer:Hematologic cancer:Hematologic cancer:

di idi i RadiationRadiation BenzeneBenzene TYPESTYPES: : AMLAML, CML, CML

Cli i l fi diCli i l fi di Clinical findings:Clinical findings: Weakness, malaise, anorexia, fever, easy Weakness, malaise, anorexia, fever, easy bruisabilirtybruisabilirty, ,

PallorPallor hepatosplenomegalyhepatosplenomegaly lymphadenopathylymphadenopathy anemiaanemiaPallor, Pallor, hepatosplenomegalyhepatosplenomegaly, , lymphadenopathylymphadenopathy, anemia, , anemia, thrombocytopenia, thrombocytopenia, leukocytosisleukocytosis or or leukopenialeukopenia

Acceptable exposure:Acceptable exposure:Acceptable exposure:Acceptable exposure:Max.permissibleMax.permissible dose =5 dose =5 remsrems

Benzene Benzene 1ppm =controversy1ppm =controversyHematologic Hematologic Periodic Periodic

screening test isscreening test is necessarynecessaryscreening test is screening test is necessarynecessary..