Occupational Hematology

1

Human red blood cells ,erythrocytes, and activated platelets ,thrombocytes, trapped in a fibrin blood clot.

2

Exposure to hematotoxins may affect :

►RBC survival (denaturation & hemolysis)

► Metabolism ( porphyria )

►Formation ( aplasia )

► Morphology & function ( preleukemia & leukemia )

► Coagulation ( thrombocytopenia )

3

DISORDERS

ASSOSIATED WITH

SHORTENED RBC

SURVIVAL4

Methemoglobinemia :

First recognized in 1800 , when coal tars converted to many products, such as anilines , nitrobenzens and quinones.

Workers work in this plants known as blue workers .

5

Aniline

◘ Aromatic nitro & amino compounds are used as intermediates in the synthesis of :

¤ aniline dyes , ¤ rubber industry ,¤ production of pesticides , ¤ plastics ,¤ paints & varnishes.

◘ readily penetrate intact skin (through intact skin ever through clothing ). Other routs : lung , ingestion .

◘ converted in liver to phenylhydroxylamine ( a catalyst in mediating hemoglobine oxidation ). 6

Clinical presentation

◘ Symptoms vary depending on the concentration of met.Hb.

◘ Most case are mild & transient (asymptomatic blueness of lips and nails bed).

◘ Pulse oximetry may indicate normoxia or mild hypoxia not reflective of severity of met.Hb.

◘ ABG may show a normal o2 tension ( Po2 ) ; co-oxmetery will reveal met .Hb reliably.

7

Prevention

◘ The most important is preventing atomospheric & cutanous exposure to oxidizing chemicals such as coal tar products.

◘ Identification of susceptible individuals ; ( G6PD.D )

◘ Biologic monitoring : measurment of meth.Hb & retic count.

8

% Methemoglobinemi

a

symptoms

10-30 Cyanosis, mild fatigue , tachycardia

30-50Weakness , breathlessness , headache , exercise intolerance

50-70 altered consciousness

> 70-80 Coma , death9

Treatment

◘ Removal of affending agent.

◘ Removal of clothing & decontamination.

◘ Mild intoxcation ( < 20% meth.Hb) : observation.

◘ Mod to sever intoxication ( > 30% blood meth.Hb ) :100% o2 by mask and antidote ( methylen blue ).

10

Chlorate salts

◘ Used primarily in pesticides and herbicides.

◘ unresponsive to methylene blue.

◘ in hemodialysis when the water supply contain chloramines ( disinfectant)

◘ Treatment : is supportive ( no antidote ) , exchange for sever cases.

11

HEMOLYSIS DUE TO HEAVY METALS

◘Included arsenic , lead, marcury , copper , autimony & others.

◘The mechanism is unknown ( affinity to thiol groups found on surface of RBCs and in Hb).

12

Arsine

◘Arsine is 2.5 time denser than air .

◘Most occ . Exposure : smelting, refining & chemical industries .

◘Respiratory tract is the most imprtant portal of entry.

HEAVY METALS

13

14

Clinical presentation◘ Acute & massive hemolysis

◘ Symptoms maybe delayed 2-24 hours after exposure .

◘ Nausea , vomiting , abd.cramping , headache , malaise , dyspnea

◘ Tea color urine ( painless )

◘ Garlicky odor of arsine , fever , tachycardia . Tachypnea , hypotension

◘ Late : jaundice & generalized nonspecific abdominal tenderness.

Arsine

15

Arsine

◘ Hemoglobinuria the earliest lab finding.

◘ Haptoglobin , free hemoglobin level (> 2000mg /dl / NL < 1 mg /dl)

◘ Brownish red plasma (due to methalbumin)

◘ Reticulocytosis , total bili , DIC , PT , cr

16

Treatment ( arsine )

◘Vigorous hydration , exchange transfusion ( for sever hemolysis)

17

lead

◘ Sever hemolysis is rare ( high atmospheric exposure; power sanding & use of blowtorch)

18

copper

◘ Copper sulfat is used ( in india ) as white washing & leather industry.

◘ Toxicity : ( ingestion or suicidal ) hemolysis , meth.Hb ,RF & death.

◘ Th.X : nonspecific , supportive; transfusion & hemodialysis.

19

THE PORPHYRIAS

20

THE PORPHYRIAS

◘ Characterized by abnormalities result in ab.NL accumulation of heme precursors.

◘ Clinical syndroms include : neurotoxicity or cutanous photosensitivity.

21

THE PORPHYRIAS cont

◘ Cutaneous photosensitivity◘ This is the result of the relatively urine – insoluble heme

precursors uroporphyrin III , coproporphyrin III & protoporphyrin VI , fluorescing in the skin following absorbtion of 400 nm electromagnetic radiation.

◘ Discoloration of teeth and occasionally hemolysis of erythrocytes.

22

THE PORPHYRIAS cont

Hexachlorobenzene

◘ Out break of aquired P( cutanous ) in turkey between 1955-58

◘ kara yara or black sore.

◘ Mortality rate was 95% among breast feed infants.

◘ pembe yara ( pink sore)

23

Herbicides: A number of report from Dicholorophenol &

Tricholorophenol

Aluminum:

A porphyria cutana tarda like syndrome is described in patients with chronic renal failure on regular hemolysis.

Vinyl chloride:

Is a known hepatotoxin Studies & report of elevation of urinary coproporphyrin &

manifestation of dx.24

lead

◘ Lead intoxication ( > 60 mg/dl in adults & > 25 mgr/dl in children ) cause sings & symptoms similar to acut intermmitent porphyria. (classic : abd.pain , constipation , vomiting )

◘ Other charactricties : neuromuscular pain , paresis, paralysis , paresthesia , diarrhea , seizures.

25

Differences between classic acute I. porphyria & lead toxicity :

1. Increase in neuropsychiatric singns in acute intermittent pophyria

2. Anemia in lead intoxication ( microcytic anemia with basophilic stippling of erythrocytes & sideroblasts in BM).

26

Treatment ( porphyrias )

Avoiding exposure

?? Phlebotomy ( in case of iron overload ).

High dose carbohydrate or hematin.

For lead : prevention is best Rx; chelators .

27

ACQUIRED PORPHYRIAToxin Use

Hexachlorobenzene Fungicide

2,4 –Dichlorophenol Herbicide

2,4,5 – trichlorophenol Herbicide

2,3,7,8 – tetrachlorodibenzo-p-dioxin Herbicide contaminant

0-benzyl-p-chlorophenol Cleanser and disinfectant

2-benzyl-p-dichlorophenol Commerical disinfectant

Vinyl chloride Plastics

Lead Paint compounds

aluminum Phosphorus binder28

29

DISORDERS ASSOCIATED

WITH DECREASED

OXYGEN SATURATION

DISORDERS ASSOCIATED WITH DECREASED OXYGEN SATURATION

1- carbon monoxide poisoning :

◘ Odorless – colorless , nonirritating gas produced by the incomplete combustion of organic materials.( hydrocarbons).

◘ Workers at risk : automobile mechanics , fire fighters , chemical workers exposed to methylene chloride. (converted to co in vivo).

30

Clinical findings ( co )

◘ General malaise , headache , nausea , dyspnea , vomiting , alteration in mental

◘ Symptom of anoxia without cyanosis (cherry – red - color)

Lab findings

◘ Chronic low level : polycythemia - higher level : hypoxia

◘ Level less than 6% : impairment in vision and time discrimination

◘ 40-60 % : altretion in mental status & death

◘ Blood carboxyhemoglobin level can be elevated after intense exposure of short duration and after chronic low level

31

Treatment ( co )

◘ Low level without symptoms : removal form source of exposure

◘ Higher level or symptomatic : hyperbaric o2

◘ Prevention : adequate ventilation

32

33

WORK – RELATED APLASTIC ANEMIA & HEMATOLOGIC

CA

WORK – RELATED APLASTIC ANEMIA & HEMATOLOGIC CA

aplastic anemia

◘ 50 % idiopatic & 50% secondary ( drugs , chemicals , radiation infection & immonologic mechanism ).

◘ Of secondary largely is caused by theraputic drugs .

34

Benzene◘ Exposure : rubber manufacturing , shoe making ,

petroleum & chemical production , printing , steel working.

◘ Great variation in susceptibility seen & evidence of poisoning sometimes appearing after weeks or years.

◘ Direct relation of amount & duration of exposure .

◘ Prognosis is better than idiopathic ( up to 40% recovery).

◘ Association with acute no lymphocytic leukemia & CML .

◘ Treatment : supportive ( transfusion & G.M.C.S.F),BM transplantation.

35

Ionizing radiation

◘ Dose – dependent manner.

◘ Internal exposure & external exposure ( more common).

◘ The most common late disturbance is leukemia .

36

CHEMICAL USE

Benzene

Intermediate in the synthesis of fabrics , pesticides , rubber ; solvent for glues, varnishes , inks , paints , octane booster for gasoline

Trinitrotoluene (TNT) Production of explosives

Hexachlorocyclohexan (lindane) pentachlorophenol Chlorophenothane (DDT)

Pesticides

ArsenicManufacture of glass , paint , enamels ,weed killers , tanning agent , pesticides

Ethylene glycol monomethyl or monobutyl ether

Production of paints ,lacquers , dyes, inks , cleaning agents

37

Mylodysplastic syndroms

◘ Benzene & ionizing radiation implicated.

◘ Several case reposts : exposure to pesticides ,solvents , farming , textile work , health professions.

◘ Lab data : cytopnea and MCV.

◘ Thx : bone marrow transplantation.

38

Multiple myeloma

◘ There is no definitive link between occupational exposure & risk of M.M

◘ Exposure : petroleum products , organic solvents , heavy metals , pesticides & asbestosis . ( all are hypothetical)

◘ Worker at risk : agricultural workers , chemical workers , miners , smelters , stokers , furniture workers

◘ High dose radiation has confirmed relation 39

Toxic thrombocytopeniaToxic agent Use mechanism

Toluene diisocyanate Polymerizing agent immune

2,2-dichlorovinyl -dimethylphosphateDieldrinPyrethrinHexachlorocyclohexa-ne (lindane)Chlorophenothane (DDT)

insecticide Megakaryocyte hypoplasia

Turpentine Organic solvent immune

Vinyl chloride plasticsLiver insufficiency with hypersplenism

40

41

Thanks for your kind attention