Oxford Handbook of Occupational Health (2 edn)
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Bone marrow aplasia
Causal exposures/industries
Ionizing radiation: acute (usually accidental) exposure to a dose of ionizing radiation above ~0.2Sv produces marrow hypoplasia/aplasia as a deterministic (dose-related) effect.
nuclear industry
medical radiography and nuclear medicine
industrial radiography
Benzene: chronic exposure above approximately 50ppm produces a range of haematotoxic effects including marrow suppression.
rubber and shoe industries
plastics production
explosives production
motor vehicle repair.
Clinical features
Haematopoietic stem cell hypoplasia leads to peripheral blood cytopenias. The clinical features vary according to the severity of stem cell suppression, and the cell lines that are affected (erythrocytes, leucocytes, and platelets), but include combinations of:
Anaemia:
fatigue
dyspnoea
Neutropenia/lymphopenia: ↑ incidence of bacterial infections
Thrombocytopenia:
petechiae and ecchymoses
gingival bleeding
↑ risk of serious bleeds, e.g. renal or GI.
Radiation exposure
Following acute exposures, the peripheral blood lymphocyte count falls within 24–48h (because of rapid cell death). Other cell lines are not destroyed immediately. Although unable to divide, damaged neutrophils and platelets can survive for up to 2–3wks, and red cells for up to 100 days. Therefore, there is a delay of 1–3wks before pancytopenia develops because of failure of replacement from marrow stem cells
Treatment for victims of serious exposures is intensive multi-system support, transfusions of red cells and platelets, and management of acute infection with appropriate antibiotics. In severe cases, erythropoietin and colony-stimulating factors (e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF)) are used to facilitate stem cell function. Bone marrow transplantation is possible, but the success rate is very low
Prognosis depends on the dose:
dose of ≥1Sv has a fatality rate of at least 10%; at <1Sv recovery from a nadir in peripheral blood counts at 4–6wks is usual. Normal blood counts re-established 2–3mths after the exposure incident
dose of 3–4Sv has a 50% fatality rate at 30 days post-exposure.
Prevention
Health surveillance
Ionizing radiation: ‘classified’ workers under the Ionizing Radiation Regulations (personal exposure >6mSv or 3/10ths of any other exposure limit) require baseline medical assessment plus periodic reviews (usually annual) of dosimetry results and sickness absence records (see 
p.
542, Ionizing Radiation Regulations).
Benzene: appropriate health surveillance for benzene would be a health record, as described in the COSHH Regulations. Routine periodic screening of haematological indices is probably inappropriate with adequate risk controls.
Relevant legislation
The following are reportable under RIDDOR:
blood dyscrasias that are attributable to ionizing radiation
benzene poisoning
The approved dosimetry service should be informed in the event of a radiation accident.
Anaemia
Anaemia can be caused by a number of (acute or chronic) occupational exposures, and by a number of different mechanisms including impairment of haem synthesis, marrow suppression, and haemolysis. Marrow suppression and haemolysis are covered separately in p.
324, Bone marrow aplasia and p.
329, Haemolysis.
Impaired haemoglobin synthesis
Exposures/industries
Lead is the classical occupational exposure associated with impaired haemoglobin synthesis
Industries:
lead smelting
battery manufacture
demolition
glass making.
Mechanism
Lead, through its high affinity for binding to sulphydryl groups, inhibits important enzymes in the haem synthesis pathway (see Fig. 15.1).
Haem synthesis.
Clinical features
Mild anaemia, which may play little or no part in the fatigue that is commonly associated with lead poisoning
Associated features include palsies due to peripheral neuropathy, arthralgia, and (rarely) confusion due to encephalopathy
The characteristic finding on investigation is basophilic stippling of erythrocytes on a peripheral blood film
Blood lead levels >80μg/dL.
Prevention
Prevention is by substitution and exposure control (see p.
538, Control of Lead at Work Regulations 2002).
Health surveillance
Statutory surveillance includes baseline and periodic screening (intervals are specified by individual susceptibility (e.g. women and young people) and exposure level). For health surveillance for inorganic lead, see p.
434, Inorganic lead.
Compensation
Anaemia with haemoglobin ≤9g/dL and a blood film showing punctate basophilia is prescribed (C1(a)) for Industrial Injuries Disablement Benefit in those who are exposed to lead.
Relevant legislation
Lead poisoning is reportable under RIDDOR.
Methaemoglobinaemia
Methaemoglobinaemia arises when the ferrous iron moiety in haem is oxidized into the ferric form. The consequence is a decreased oxygen-carrying capacity of haemoglobin. It can be caused by a number of acute occupational exposures.
Causative agents
Ferricyanide
Bivalent copper
Chromates
Chlorates
Quinones
Dyes with a high oxidation–reduction potential
Nitrite, often used as a preservative, is one of the most common methaemoglobin-forming agents
Aniline dye derivatives.
Clinical features
Cyanosis
Dyspnoea
Headaches and dizziness
Muscle weakness
Peripheral blood film shows mild anaemia and erythrocyte abnormalities (Heinz bodies and punctate polychromasia).
Individual susceptibility
Hereditary methaemoglobin reductase deficiency.
Treatment
Acute treatment is with methylene blue (methylthioninium chloride), administered by slow IV infusion. Management of acute poisoning is covered in detail on p.
808, Methaemoglobinaemia (acute treatment).
Methylthioninium chloride may cause brisk haemolysis in those with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Relevant legislation
Acute poisoning with a nitro-, chloro-, or amino- derivative of benzene is reportable under RIDDOR.
Haemolysis
Haemolysis is the process of premature red blood cell destruction.
Clinical features and treatment
Acute:
haemoglobinuria, jaundice, and abdominal pain
methaemoglobinaemia and methaemoglobinuria
complicated by anuric renal failure
exchange blood transfusion is life-saving in severe cases
Chronic:
anaemia
reticulocytosis due to ↑ red cell production is the hallmark of haemolysis.
Exposures
Arsine gas:
industries—micro-electronics industry (semiconductor manufacture), metal smelting, plating, galvanizing, and soldering
effects occur with acute poisoning at exposures >3ppm for several hours, or >20ppm for <1h
chronic low-level exposure can cause anaemia with mild ↑ bilirubin
diagnosis is based on history of exposure and ↑ urinary arsenic
Naphthalene:
industries—manufacture of plastics and dyestuffs, mothballs, biocides for the wood industry
can precipitate haemolysis in individuals with G6PD deficiency
Rare occupational exposures associated with haemolysis include:
potassium chlorate
pyrogallic acid
stibine gas (rare accidental exposure).
Prevention
Prevention is by substitution and exposure control.
Haematological malignancies
Leukaemias
Exposures
Two exposures have a well-established association with leukaemia.
Ionizing radiation: leukaemogenesis is a late stochastic effect of ionizing radiation (no dose threshold for the effect). The following have been noted in excess among radiation workers:
acute myeloid leukaemia (AML)
acute lymphoblastic leukaemia (ALL)
chronic myeloid leukaemia (CML)
Benzene: AML.
Other exposures (or job/industry used as a marker, but with the exact exposure unclear) have been implicated with small increases in leukaemia risk. Most studies have been small, and in many there is a problem with confounding by benzene exposure.
Possible ↑ leukaemia risk:
1,3-butadiene
ethylene oxide.
Clinical features
Presents with a combination of anaemia, bleeding, and infection.
Compensation
Acute non-lymphatic leukaemia is prescribed (C7) for Industrial Injuries Disablement Benefit in those who are exposed to benzene.
Lymphoproliferative disorders
Exposures
Ionizing radiation: the following have been noted in excess among radiation workers, and are late stochastic effects:
multiple myeloma
non-Hodgkin’s lymphoma.
Clinical features
Presents with anaemia or local mass.
Treatment and prognosis of haematological malignancies
Treatment is complex and beyond the scope of this book. However, the usual approach includes chemotherapy regimes +/– radiotherapy +/– bone marrow transplant. The prognosis for treated acute leukaemias has improved significantly in the past 10yrs.
Prevention
Prevention is through exposure control. See p.
542, Ionizing Radiation Regulations 1999.
