Beyond the broad concept of stress and its relationship to general health issues, there has been little attention to the role of psychiatric diagnosis in the prevention and treatment of the mental health consequences of work-related injuries. Most of the work on job stress has been concerned with the effects of exposure to stressful conditions over time, rather than to problems associated with a specific event such as a traumatic or life-threatening injury or the witnessing of an industrial accident or act of violence. At the same time, Post-traumatic Stress Disorder (PTSD), a condition which has received considerable credibility and interest since the mid-1980s, is being more widely applied in contexts outside of cases involving war trauma and victims of crime. With respect to the workplace, PTSD has begun to appear as the medical diagnosis in cases of occupational injury and as the emotional outcome of exposure to traumatic situations occurring in the workplace. It is often the subject of controversy and some confusion with respect to its relationship to work conditions and the responsibility of the employer when claims of psychological injury are made. The occupational health practitioner is called upon increasingly to advise on company policy in the handling of these exposures and injury claims, and to render medical opinions with respect to the diagnosis, treatment and ultimate job status of these employees. Familiarity with PTSD and its related conditions is therefore increasingly important for the occupational health practitioner.

The following topics will be reviewed in this article:

• differential diagnosis of PTSD with other conditions such as primary depression and anxiety disorders
• relationship of PTSD to stress-related somatic complaints
• prevention of post-traumatic stress reactions in survivors and witnesses of psychologically traumatic events occurring in the workplace
• prevention and treatment of complications of work injury related to post-traumatic stress.

Post-traumatic Stress Disorder affects people who have been exposed to traumatizing events or conditions. It is characterized by symptoms of numbing, psychological and social withdrawal, difficulties controlling emotion, especially anger, and intrusive recollection and reliving of experiences of the traumatic event. By definition, a traumatizing event is one that is outside the normal range of everyday life events and is experienced as overwhelming by the individual. A traumatic event usually involves a threat to one’s own life or to someone close, or the witnessing of an actual death or serious injury, especially when this occurs suddenly or violently.

The psychiatric antecedents of our current concept of PTSD go back to the descriptions of “battle fatigue” and “shell shock” during and after the World Wars. However, the causes, symptoms, course and effective treatment of this often debilitating condition were still poorly understood when tens of thousands of Vietnam-era combat veterans began to appear in the US Veterans Administration Hospitals, offices of family doctors, jails and homeless shelters in the 1970s. Due in large part to the organized effort of veterans’ groups, in collaboration with the American Psychiatric Association, PTSD was first identified and described in 1980 in the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM III) (American Psychiatric Association 1980). The condition is now known to affect a wide range of trauma victims, including survivors of civilian disasters, victims of crime, torture and terrorism, and survivors of childhood and domestic abuse. Although changes in the classification of the disorder are reflected in the current diagnostic manual (DSM IV), the diagnostic criteria and symptoms remain essentially unchanged (American Psychiatric Association 1994).

Diagnostic Criteria for Post-TraumaticStress Disorder

A. The person has been exposed to a traumatic event in which both of the following were present:

1. The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others.
2. The person’s response involved intense fear, helplessness or horror.

B. The traumatic event is persistently re-experienced in one (or more) of the following ways:

1. Recurrent and intrusive distressing recollections of the event, including images, thoughts or perceptions.
2. Recurrent distressing dreams of the event.
3. Acting or feeling as if the traumatic event were recurring.
4. Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.
5. Physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.

C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the following:

1. Efforts to avoid thoughts, feelings or conversations associated with the trauma.
2. Efforts to avoid activities, places or people that arouse recollections of the trauma.
3. Inability to recall an important aspect of the trauma.
4. Markedly diminished interest or participation in significant activities.
5. Feeling of detachment or estrangement from others.
6. Restricted range of affect (e.g., unable to have loving feelings).
7. Sense of a foreshortened future (e.g., does not expect to have a career, marriage, children or a normal life span).

D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two (or more) of the following:

1. Difficulty falling or staying asleep.
2. Irritability or outbursts of anger.
3. Difficulty concentrating.
4. Hypervigilance.
5. Exaggerated startle response.

E. Duration of the disturbance (symptoms in criteria B, C and D) is more than 1 month.

F. The disturbance causes clinically significant distress or impairment in social, occupational or other important areas of functioning.

Specify if:

Acute: if duration of symptoms is less than 3 months

Chronic: if duration of symptoms is 3 months or more.

Specify if:

With Delayed Onset: if onset of symptoms is at least 6 months after the stressor.

Psychological stress has achieved increasing recognition as an outcome of work-related hazards. The link between work hazards and post-traumatic stress was first established in the 1970s with the discovery of high incident rates of PTSD in workers in law enforcement, emergency medical, rescue and firefighting. Specific interventions have been developed to prevent PTSD in workers exposed to job-related traumatic stressors such as mutilating injury, death and use of deadly force. These interventions emphasize providing exposed workers with education about normal traumatic stress reactions, and the opportunity to actively surface their feelings and reactions with their peers. These techniques have become well established in these occupations in the United States, Australia and many European nations. Job-related traumatic stress, however, is not limited to workers in these high-risk industries. Many of the principles of preventive intervention developed for these occupations can be applied to programmes to reduce or prevent traumatic stress reactions in the general workforce.

Issues in Diagnosis and Treatment

Diagnosis

The key to the differential diagnosis of PTSD and traumatic-stress-related conditions is the presence of a traumatic stressor. Although the stressor event must conform to criterion A—that is, be an event or situation that is outside of the normal range of experience—individuals respond in various ways to similar events. An event that precipitates a clinical stress reaction in one person may not affect another significantly. Therefore, the absence of symptoms in other similarly exposed workers should not cause the practitioner to discount the possibility of a true post-trauma reaction in a particular worker. Individual vulnerability to PTSD has as much to do with the emotional and cognitive impact of an experience on the victim as it does to the intensity of the stressor itself. A prime vulnerability factor is a history of psychological trauma due to a previous traumatic exposure or significant personal loss of some kind. When a symptom picture suggestive of PTSD is presented, it is important to establish whether an event that may satisfy the criterion for a trauma has occurred. This is particularly important because the victim himself may not make the connection between his symptoms and the traumatic event. This failure to connect the symptom with the cause follows the common “numbing” reaction, which may cause forgetting or dissociation of the event, and because it is not unusual for symptom appearance to be delayed for weeks or months. Chronic and often severe depression, anxiety and somatic conditions are often the result of a failure to diagnose and treat. Thus, early diagnosis is particularly important because of the often hidden nature of the condition, even to the sufferer him- or herself, and because of the implications for treatment.

Treatment

Although the depression and anxiety symptoms of PTSD may respond to usual therapies such as pharmacology, effective treatment is different from those usually recommended for these conditions. PTSD may be the most preventable of all psychiatric conditions and, in the occupational health sphere, perhaps the most preventable of all work-related injuries. Because its occurrence is linked so directly to a specific stressor event, treatment can focus on prevention. If proper preventive education and counselling are provided soon after the traumatic exposure, subsequent stress reactions can be minimized or prevented altogether. Whether the intervention is preventive or therapeutic depends largely on timing, but the methodology is essentially similar. The first step in successful treatment or preventive intervention is allowing the victim to establish the connection between the stressor and his or her symptoms. This identification and “normalization” of what are typically frightening and confusing reactions is very important for reduction or prevention of symptoms. Once the normalization of the stress response has been accomplished, treatment addresses the controlled processing of the emotional and cognitive impact of the experience.

PTSD or conditions related to traumatic stress result from the sealing off of unacceptable or unacceptably intense emotional and cognitive reactions to traumatic stressors. It is generally considered that the stress syndrome can be prevented by providing the opportunity for controlled processing of the reactions to the trauma before the sealing off of the trauma occurs. Thus, prevention through timely and skilled intervention is the keystone for the treatment of PTSD. These treatment principles may depart from the traditional psychiatric approach to many conditions. Therefore, it is important that employees at risk of post-traumatic stress reactions be treated by mental health professionals with specialized training and experience in treating trauma-related conditions. The length of treatment is variable. It will depend on the timing of the intervention, the severity of the stressor, symptom severity and the possibility that a traumatic exposure may precipitate an emotional crisis linked to earlier or related experiences. A further issue in treatment concerns the importance of group treatment modalities. Victims of trauma can achieve enormous benefit from the support of others who have shared the same or similar traumatic stress experience. This is of particular importance in the workplace context, when groups of co-workers or entire work organizations are affected by a tragic accident, act of violence or traumatic loss.

Prevention of Post-Traumatic Stress Reactionsafter Incidents of Workplace Trauma

A range of events or situations occurring in the workplace may put workers at risk of post-traumatic stress reactions. These include violence or threat of violence, including suicide, inter-employee violence and crime, such as armed robbery; fatal or severe injury; and sudden death or medical crisis, such as heart attack. Unless properly managed, these situations can cause a range of negative outcomes, including post-traumatic stress reactions that may reach clinical levels, and other stress-related effects that will affect health and work performance, including avoidance of the workplace, concentration difficulties, mood disturbances, social withdrawal, substance abuse and family problems. These problems can affect not only line employees but management staff as well. Managers are at particular risk because of conflicts between their operational responsibilities, their feelings of personal responsibility for the employees in their charge and their own sense of shock and grief. In the absence of clear company policies and prompt assistance from health personnel to deal with the aftermath of the trauma, managers at all levels may suffer from feelings of helplessness that compound their own traumatic stress reactions.

Traumatic events in the workplace require a definite response from upper management in close collaboration with health, safety, security, communications and other functions. A crisis response plan fulfils three primary goals:

1. prevention of post-traumatic stress reactions by reaching affected individuals and groups before they have a chance to seal over
2. communication of crisis-related information in order to contain fears and control rumours
3. fostering of confidence that management is in control of the crisis and demonstrating concern for employees’ welfare.

The methodology for the implementation of such a plan has been fully described elsewhere (Braverman 1992a,b; 1993b). It emphasizes adequate communication between management and employees, assembling of groups of affected employees and prompt preventive counselling of those at highest risk for post-traumatic stress because of their levels of exposure or individual vulnerability factors.

Managers and company health personnel must function as a team to be sensitive for signs of continued or delayed trauma-related stress in the weeks and months after the traumatic event. These can be difficult to identify for manager and health professional alike, because post-traumatic stress reactions are often delayed, and they can masquerade as other problems. For a supervisor or for the nurse or counsellor who becomes involved, any signs of emotional stress, such as irritability, withdrawal or a drop in productivity, may signal a reaction to a traumatic stressor. Any change in behaviour, including increased absenteeism, or even a marked increase in work hours (“workaholism”) can be a signal. Indications of drug or alcohol abuse or change in moods should be explored as possibly linked to post-traumatic stress. A crisis response plan should include training for managers and health professionals to be alert for these signs so that intervention can be rendered at the earliest possible point.

Stress-related Complications of Occupational Injury

It has been our experience reviewing workers’ compensation claims up to five years post-injury that post-traumatic stress syndromes are a common outcome of occupational injury involving life-threatening or disfiguring injury, or assault and other exposures to crime. The condition typically remains undiagnosed for years, its origins unsuspected by medical professionals, claims administrators and human resource managers, and even the employee him- or herself. When unrecognized, it can slow or even prevent recovery from physical injury.

Disabilities and injuries linked to psychological stress are among the most costly and difficult to manage of all work-related injuries. In the “stress claim”, an employee maintains he or she has been emotionally damaged by an event or conditions at work. Costly and hard to fight, stress claims usually result in litigation and in the separation of the employee. There exists, however, a vastly more frequent but seldom recognized source of stress-related claims. In these cases, serious injury or exposure to life-threatening situations results in undiagnosed and untreated psychological stress conditions that significantly affect the outcome of work-related injuries.

On the basis of our work with traumatic worksite injuries and violent episodes over a wide range of worksites, we estimate that at least half of disputed workers’ compensation claims involve unrecognized and untreated post-traumatic stress conditions or other psychosocial components. In the push to resolve medical problems and determine the employee’s employment status, and because of many systems’ fear and mistrust of mental health intervention, emotional stress and psychosocial issues take a back seat. When no one deals with it, stress can take the form of a number of medical conditions, unrecognized by the employer, the risk manager, the health care provider and the employee him- or herself. Trauma-related stress also typically leads to avoidance of the workplace, which increases the risk of conflicts and disputes regarding return to work and claims of disability.

Many employers and insurance carriers believe that contact with a mental health professional leads directly to an expensive and unmanageable claim. Unfortunately, this is often the case. Statistics bear out that claims for mental stress are more expensive than claims for other kinds of injuries. Furthermore, they are increasing faster than any other kind of injury claim. In the typical “physical-mental” claim scenario, the psychiatrist or psychologist appears only at the point—typically months or even years after the event—when there is a need for expert assessment in a dispute. By this time, the psychological damage has been done. The trauma-related stress reaction may have prevented the employee from returning to the workplace, even though he or she appeared visibly healed. Over time, the untreated stress reaction to the original injury has resulted in a chronic anxiety or depression, a somatic illness or a substance abuse disorder. Indeed, it is rare that mental health intervention is rendered at the point when it can prevent the trauma-related stress reaction and thus help the employee fully recover from the trauma of a serious injury or assault.

With a small measure of planning and proper timing, the costs and suffering associated with injury-related stress are among the most preventable of all injuries. The following are the components of an effective post-injury plan (Braverman 1993a):

Early intervention

Companies should require a brief mental health intervention whenever a severe accident, assault or other traumatic event impacts on an employee. This evaluation should be seen as preventive, rather than as tied to the standard claims procedure. It should be provided even if there is no lost time, injury or need for medical treatment. The intervention should emphasize education and prevention, rather than a strictly clinical approach that may cause the employee to feel stigmatized. The employer, perhaps in conjunction with the insurance provider, should take responsibility for the relatively small cost of providing this service. Care should be taken that only professionals with specialized expertise or training in post-traumatic stress conditions be involved.

Return to work

Any counselling or assessment activity should be coordinated with a return-to-work plan. Employees who have undergone a trauma often feel afraid or tentative about returning to the worksite. Combining brief education and counselling with visits to the workplace during the recovery period has been used to great advantage in accomplishing this transition and speeding return to work. Health professionals can work with the supervisor or manager in developing gradual re-entry into job functioning. Even when there is no remaining physical limitation, emotional factors may necessitate accommodations, such as allowing a bank teller who was robbed to work in another area of the bank for part of the day as she gradually becomes comfortable returning to work at the customer window.

Follow-up

Post-traumatic reactions are often delayed. Follow-up at 1- and 6-month intervals with employees who have returned to work is important. Supervisors are also provided with fact sheets on how to spot possible delayed or long-term problems associated with post-traumatic stress.

Summary: The Link between Post-Traumatic Stress Studies and Occupational Health

Perhaps more than any other health science, occupational medicine is concerned with the relationship between human stress and disease. Indeed, much of the research in human stress in this century has taken place within the occupational health field. As the health sciences in general became more involved in prevention, the workplace has become increasingly important as an arena for research into the contribution of the physical and psychosocial environment to disease and other health outcomes, and into methods for the prevention of stress-related conditions. At the same time, since 1980 a revolution in the study of post-traumatic stress has brought important progress to the understanding of the human stress response. The occupational health practitioner is at the intersection of these increasingly important fields of study.

As the landscape of work undergoes revolutionary transformation, and as we learn more about productivity, coping and the stressful impact of continued change, the line between chronic stress and acute or traumatic stress has begun to blur. The clinical theory of traumatic stress has much to tell us about how to prevent and treat work-related psychological stress. As in all health sciences, knowledge of the causes of a syndrome can help in prevention. In the area of traumatic stress, the workplace has shown itself to be an excellent place to promote health and healing. By being well acquainted with the symptoms and causes of post-traumatic stress reactions, occupational health practitioners can increase their effectiveness as agents of prevention.

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Leukaemias

Leukaemias constitute 3% of all cancers worldwide (Linet 1985). They are a group of malignancies of blood precursor cells, classified according to cell type of origin, degree of cellular differentiation, and clinical and epidemiological behaviour. The four common types are acute lymphocytic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), acute myelocytic leukaemia (AML) and chronic myelocytic leukaemia (CML). ALL develops rapidly, is the most common form of leukaemia in childhood and originates in the white blood corpuscles in the lymph nodes. CLL arises in bone marrow lymphocytes, develops very slowly and is more common in aged persons. AML is the common form of acute leukaemia in adults. Rare types of acute leukaemia include monocytic, basophilic, eosinophilic, plasma-, erythro- and hairy-cell leukaemias. These rarer forms of acute leukaemia are sometimes lumped together under the heading acute non-lymphocytic leukaemia (ANLL), due in part to the belief that they arise from a common stem cell. Most cases of CML are characterized by a specific chromosomal abnormality, the Philadelphia chromosome. The eventual outcome of CML often is leukaemic transformation to AML. Transformation to AML also can occur in polycythaemia vera and essential thrombocythaemia, neoplastic disorders with elevated red cell or platelet levels, as well as myelofibrosis and myeloid dysplasia. This has led to characterizing these disorders as related myeloproliferative diseases.

The clinical picture varies according to the type of leukaemia. Most patients suffer from fatigue and malaise. Haematological count anomalies and atypical cells are suggestive of leukaemia and indicate a bone marrow examination. Anaemia, thrombocytopenia, neutropenia, elevated leucocyte count and elevated number of blast cells are typical signs of acute leukaemia.

Incidence: The annual overall age-adjusted incidence of leukaemias varies between 2 and 12 per 100,000 in men and between 1 and 11 per 100,000 in women in different populations. High figures are encountered in North American, western European and Israeli populations, while low ones are reported for Asian and African populations. The incidence varies according to age and to type of leukaemia. There is a marked increase in the incidence of leukaemia with age, and there is also a childhood peak which occurs around two to four years of age. Different leukaemia subgroups display different age patterns. CLL is about twice as frequent in men as in women. Incidence and mortality figures of adult leukaemias have tended to stay relatively stable over the past few decades.

Risk factors: Familial factors in the development of leukaemia have been suggested, but the evidence for this is inconclusive. Certain immunological conditions, some of which are hereditary, appear to predispose to leukaemia. Down’s syndrome is predictive of acute leukaemia. Two oncogenic retroviruses (human T-cell leukaemia virus-I, human T-lymphotropic virus-II) have been identified as being related to the development of leukaemias. These viruses are thought to be early-stage carcinogens and as such are insufficient causes of leukaemia (Keating, Estey and Kantarjian 1993).

Ionizing radiation and benzene exposure are established environmental and occupational causes of leukaemias. The incidence of CLL, however, has not been associated with exposure to radiation. Radiation and benzene-induced leukaemias are recognized as occupational diseases in a number of countries.

Much less consistently, leukaemia excesses have been reported for the following groups of workers: drivers; electricians; telephone linepersons and electronic engineers; farmers; flour millers; gardeners; mechanics, welders and metal workers; textile workers; paper-mill workers; and workers in the petroleum industry and distribution of petroleum products. Some particular agents in the occupational environment have been consistently associated with increased risk of leukaemia. These agents include butadiene, electromagnetic fields, engine exhaust, ethylene oxide, insecticides and herbicides, machining fluids, organic solvents, petroleum products (including gasoline), styrene and unidentified viruses. Paternal and maternal exposures to these agents prior to conception have been suggested to increase the leukaemia risk in the offspring, but the evidence at this time is insufficient to establish such exposure as causative.

Treatment and prevention: Up to 75% of male cases of leukaemia may be preventable (International Agency for Research on Cancer 1990). Avoidance of exposure to radiation and benzene will reduce the risk of leukaemias, but the potential reduction worldwide has not been estimated. Treatments of leukaemias include chemotherapy (single agents or combinations), bone marrow transplant and interferons. Bone marrow transplant in both ALL and AML is associated with a disease-free survival between 25 and 60%. The prognosis is poor for patients who do not achieve remission or who relapse. Of those who relapse, about 30% achieve a second remission. The major cause of failure to achieve remission is death from infection and haemorrhage. The survival of untreated acute leukaemia is 10% within 1 year of diagnosis. The median survival of patients with CLL before the initiation of treatment is 6 years. The length of survival depends on the stage of the disease when the diagnosis is initially made.

Leukaemias may occur following medical treatment with radiation and certain chemotherapeutic agents of another malignancy, such as Hodgkin’s disease, lymphomas, myelomas, and ovarian and breast carcinomas. Most of these secondary cases of leukaemia are acute non-lymphocytic leukaemias or myelodysplastic syndrome, which is a preleukaemic condition. Chromosomal abnormalities appear to be more readily observed in both treatment-related leukaemias and in leukaemias associated with radiation and benzene exposure. These acute leukaemias also share a tendency to resist therapy. Activation of the ras oncogene has been reported to occur more frequently in patients with AML who worked in professions deemed to be at high risk of exposure to leukaemogens (Taylor et al. 1992).

Malignant Lymphomas and Multiple Myeloma

Malignant lymphomas constitute a heterogeneous group of neoplasms primarily affecting lymphoid tissues and organs. Malignant lymphomas are divided into two major cellular types: Hodgkin’s disease (HD) (International Classification of Disease, ICD-9 201) and non-Hodgkin lymphomas (NHL) (ICD-9 200, 202). Multiple myeloma (MM) (ICD-9 203) represents a malignancy of plasma cells within the bone marrow and accounts usually for less than 1% of all malignancies (International Agency for Research on Cancer 1993). In 1985, malignant lymphomas and multiple myelomas ranked seventh among all cancers worldwide. They represented 4.2% of all estimated new cancer cases and amounted to 316,000 new cases (Parkin, Pisani and Ferlay 1993).

Mortality and incidence of malignant lymphomas do not reveal a consistent pattern across socio-economic categories worldwide. Children’s HD has a tendency to be more common in less developed nations, while relatively high rates have been observed in young adults in countries in more developed regions. In some countries, NHL seems to be in excess among people in higher socio-economic groups, while in other countries no such clear gradient has been observed.

Occupational exposures may increase the risk of malignant lymphomas, but the epidemiological evidence is still inconclusive. Asbestos, benzene, ionizing radiation, chlorinated hydrocarbon solvents, wood dust and chemicals in leather and rubber-tire manufacturing are examples of agents that have been associated with the risk of unspecified malignant lymphomas. NHL is more common among farmers. Further suspect occupational agents for HD, NHL and MM are mentioned below.

Hodgkin’s disease

Hodgkin’s disease is a malignant lymphoma characterized by the presence of multinucleated giant (Reed-Sternberg) cells. Lymph nodes in the mediastinum and neck are involved in about 90% of the cases, but the disease may occur in other sites as well. Histological subtypes of HD differ in their clinical and epidemiological behaviour. The Rye classification system includes four subtypes of HD: lymphocytic predominance, nodular sclerosis, mixed cellularity and lymphocytic depletion. The diagnosis of HD is made by biopsy and treatment is radiation therapy alone or in combination with chemotherapy.

The prognosis of HD patients depends on the stage of the disease at diagnosis. About 85 to 100% of patients without massive mediastinal involvement survive for about 8 years from the start of the treatment without further relapse. When there is massive mediastinal involvement, about 50% of the cases suffer a relapse. Radiation therapy and chemotherapy may involve various side effects, such as secondary acute myelocytic leukaemia discussed earlier.

The incidence of HD has not undergone major changes over time but for a few exceptions, such as the populations of the Nordic countries, in which the rates have declined (International Agency for Research on Cancer 1993).

Available data show that in the 1980s the populations of Costa Rica, Denmark and Finland had median annual incidence rates of HD of 2.5 per 100,000 in men and 1.5 per 100,000 in women (standardized to world population); these figures yielded a sex ratio of 1.7. The highest rates in males were recorded for populations in Italy, the United States, Switzerland and Ireland, while the highest female rates were in the United States and Cuba. Low incidence rates have been reported for Japan and China (International Agency for Research on Cancer 1992).

Viral infection has been suspected as involved in the aetiology of HD. Infectious mononucleosis, which is induced by the Epstein-Barr virus, a herpes virus, has been shown to be associated with increased risk of HD. Hodgkin’s disease may also cluster in families, and other time-space constellations of cases have been observed, but the evidence that there are common aetiological factors behind such clusters is weak.

The extent to which occupational factors can lead to increased risk for HD has not been established. There are three predominant suspect agents—organic solvents, phenoxy herbicides and wood dust—but the epidemiological evidence is limited and controversial.

Non-Hodgkin lymphoma

About 98% of the NHLs are lymphocytic lymphomas. At least four different classifications of lymphocytic lymphomas have been commonly used (Longo et al. 1993). In addition, an endemic malignancy, Burkitt’s lymphoma, is endemic in certain areas of tropical Africa and New Guinea.

Thirty to fifty per cent of NHLs are curable with chemotherapy and/or radiotherapy. Bone marrow transplants may be necessary.

Incidence: High annual incidences of NHL (over 12 per 100,000, standardized to world standard population) have been reported during the 1980s for the White population in the United States, particularly San Francisco and New York City, as well as in some Swiss cantons, in Canada, in Trieste (Italy) and Porto Alegre (Brazil, in men). The incidence of NHL is usually higher in men than in women, with the typical excess in men being 50 to 100% greater than in women. In Cuba, and in the White population of Bermuda, however, the incidence is slightly higher in women (International Agency for Research on Cancer 1992).

NHL incidence and mortality rates have been rising in a number of countries worldwide (International Agency for Research on Cancer 1993). By 1988, the average annual incidence in US White men increased by 152%. Some of the increase is due to changes in diagnostic practices of physicians and part due to an increase in immunosuppressive conditions which are induced by the human immunodeficiency virus (HIV, associated with AIDS), other viruses and immunosuppressive chemotherapy. These factors do not explain the entire increase, and a considerable proportion of residual increase may be explained by dietary habits, environmental exposures such as hair dyes, and possibly familial tendencies, as well as some rare factors (Hartge and Devesa 1992).

Occupational determinants have been suspected to play a role in the development of NHL. It is currently estimated that 10% of NHLs are thought to be related to occupational exposures in the United States (Hartge and Devesa 1992), but this percentage varies by time period and location. The occupational causes are not well established. Excess risk of NHL has been associated with electric power plant jobs, farming, grain handling, metal working, petroleum refining and woodworking, and has been found among chemists. Occupational exposures that have been associated with an increased NHL risk include ethylene oxide, chlorophenols, fertilizers, herbicides, insecticides, hair dyes, organic solvents and ionizing radiation. A number of positive findings for phenoxyacetic acid herbicide exposure have been reported (Morrison et al. 1992). Some of the herbicides involved were contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD). The epidemiological evidence for occupational aetiologies of NHL is still limited, however.

Multiple myeloma

Multiple myeloma (MM) involves predominantly bone (especially the skull), bone marrow and kidney. It represents malignant proliferation of B-lymphocyte-derived cells that synthesize and secrete immunoglobulins. The diagnosis is made using radiology, a test for the MM-specific Bence-Jones proteinuria, determination of abnormal plasma cells in the bone marrow, and immunoelectrophoresis. MM is treated with bone marrow transplantation, radiation therapy, conventional chemotherapy or polychemotherapy, and immunological therapy. Treated MM patients survive 28 to 43 months on the average (Ludwig and Kuhrer 1994).

The incidence of MM increases sharply with increasing age. High age-standardized annual incidence rates (5 to 10 per 100,000 in men and 4 to 6 per 100,000 in women) have been encountered in the United States Black populations, in Martinique and among the Maoris in New Zealand. Many Chinese, Indian, Japanese and Filipino populations have low rates (less than 10 per 100,000 person-years in men and less than 0.3 per 100,000 person-years in women) (International Agency for Research on Cancer 1992). The rate of multiple myeloma has been on the increase in Europe, Asia, Oceania and in both the Black and White United States populations since the 1960s, but the increase has tended to level off in a number of European populations (International Agency for Research on Cancer 1993).

Throughout the world there is an almost consistent excess among males in the incidence of MM. This excess is typically of the order of 30 to 80%.

Familial and other case clusterings of MM have been reported, but the evidence is inconclusive as to the causes of such clusterings. The excess incidence among the United States Black population as contrasted with the White population points towards the possibility of differential host susceptibility among population groups, which may be genetic. Chronic immunological disorders have on occasion been associated with the risk of MM. The data on social class distribution of MM are limited and unreliable for conclusions on any gradients.

Occupational factors: Epidemiological evidence of an elevated risk of MM in gasoline-exposed workers and refinery workers suggests a benzene aetiology (Infante 1993). An excess of multiple myeloma has repeatedly been observed in farmers and farm workers. Pesticides represent a suspect group of agents. The evidence for carcinogenicity is, however, insufficient for phenoxyacetic acid herbicides (Morrison et al. 1992). Dioxins are sometimes impurities in some phenoxyacetic acid herbicides. There is a reported significant excess of MM in women residing in a zone contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin after an accident in a plant near Seveso, Italy (Bertazzi et al. 1993). The Seveso results were based on two cases which occurred during ten years of follow-up, and further observation is needed to confirm the association. Another possible explanation for the increased risk in farmers and farm workers is exposure to some viruses (Priester and Mason 1974).

Further suspect occupations and occupational agents that have been associated with increased risk of MM include painters, truck drivers, asbestos, engine exhaust, hair-colouring products, radiation, styrene, vinyl chloride and wood dust. The evidence for these occupations and agents remains inconclusive.

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“An emerging global economy mandates serious scientific attention to discoveries that foster enhanced human productivity in an ever-changing and technologically sophisticated work world” (Human Capital Initiative 1992). Economic, social, psychological, demographic, political and ecological changes around the world are forcing us to reassess the concept of work, stress and burnout on the workforce.

Productive work “calls for a primary focus on reality external to one self. Work therefore emphasizes the rational aspects of people and problem solving” (Lowman 1993). The affective and mood side of work is becoming an ever-increasing concern as the work environment becomes more complex.

A conflict that may arise between the individual and the world of work is that a transition is called for, for the beginning worker, from the self-centredness of adolescence to the disciplined subordination of personal needs to the demands of the workplace. Many workers need to learn and adapt to the reality that personal feelings and values are often of little importance or relevance to the workplace.

In order to continue a discussion of work-related stress, one needs to define the term, which has been used widely and with varying meanings in the behavioural science literature. Stress involves an interaction between a person and the work environment. Something happens in the work arena which presents the individual with a demand, constraint, request or opportunity for behaviour and consequent response. “There is a potential for stress when an environmental situation is perceived as presenting a demand which threatens to exceed the person’s capabilities and resources for meeting it, under conditions where he/she expects a substantial differential in the rewards and costs from meeting the demand versus not meeting it” (McGrath 1976).

It is appropriate to state that the degree to which the demand exceeds the perceived expectation and the degree of differential rewards expected from meeting or not meeting that demand reflect the amount of stress that the person experiences. McGrath further suggests that stress may present itself in the following ways: “Cognitive-appraisal wherein subjectively experienced stress is contingent upon the person’s perception of the situation. In this category the emotional, physiological and behavioural responses are significantly influenced by the person’s interpretation of the ‘objective’ or external stress situation.”

Another component of stress is the individual’s past experience with a similar situation and his or her empirical response. Along with this is the reinforcement factor, whether positive or negative, successes or failures which can operate to reduce or enhance, respectively, levels of subjectively experienced stress.

Burnout is a form of stress. It is a process defined as a feeling of progressive deterioration and exhaustion and an eventual depletion of energy. It is also often accompanied by a loss of motivation, a feeling that suggests “enough, no more”. It is an overload that tends during the course of time to affect attitudes, mood and general behaviour (Freudenberger 1975; Freudenberger and Richelson 1981). The process is subtle; it develops slowly and sometimes occurs in stages. It is often not perceived by the person most affected, since he or she is the last individual to believe that the process is taking place.

The symptoms of burnout manifest themselves on a physical level as ill-defined psychosomatic complaints, sleep disturbances, excessive fatigue, gastrointestinal symptoms, backaches, headaches, various skin conditions or vague cardiac pains of an unexplained origin (Freudenberger and North 1986).

Mental and behavioural changes are more subtle. “Burnout is often manifest by a quickness to be irritated, sexual problems (e.g. impotence or frigidity), fault finding, anger and low frustration threshold” (Freudenberger 1984a).

Further affective and mood signs may be progressive detachment, loss of self-confidence and lowered self-esteem, depression, mood swings, an inability to concentrate or pay attention, an increased cynicism and pessimism, as well as a general sense of futility. Over a period of time the contented person becomes angry, the responsive person becomes silent and withdrawn and the optimist becomes a pessimist.

The affect feelings that appear to be most common are anxiety and depression. The anxiety most typically associated with work is performance anxiety. The forms of work conditions that are relevant in promoting this form of anxiety are role ambiguity and role overload (Srivastava 1989).

Wilke (1977) has indicated that “one area that presents particular opportunity for conflict for the personality-disordered individual concerns the hierarchical nature of work organizations. The source of such difficulties can rest with the individual, the organization, or some interactive combination.”

Depressive features are frequently found as part of the presenting symptoms of work-related difficulties. Estimates from epidemiological data suggest that depression affects 8 to 12% of men and 20 to 25% of women. The life expectancy experience of serious depressive reactions virtually assures that workplace issues for many people will be affected at some time by depression (Charney and Weissman 1988).

The seriousness of these observations was validated by a study conducted by Northwestern National Life Insurance Company—“Employee Burnout: America’s Newest Epidemic” (1991). It was conducted among 600 workers nationwide and identified the extent, causes, costs and solutions related to workplace stress. The most striking research findings were that one in three Americans seriously thought about quitting work in 1990 because of job stress, and a similar portion expected to experience job burnout in the future. Nearly half of the 600 respondents experienced stress levels as “extremely or very high.” Workplace changes such as cutting employee benefits, change of ownership, required frequent overtime or reduced workforce tend to speed up job stress.

MacLean (1986) further elaborates on job stressors as uncomfortable or unsafe working conditions, quantitative and qualitative overload, lack of control over the work process and work rate, as well as monotony and boredom.

Additionally, employers are reporting an ever-increasing number of employees with alcohol and drug abuse problems (Freudenberger 1984b). Divorce or other marital problems are frequently reported as employee stressors, as are long-term or acute stressors such as caring for an elderly or disabled relative.

Assessment and classification to diminish the possibility of burnout may be approached from the points of view related to vocational interests, vocational choices or preferences and characteristics of people with different preferences (Holland 1973). One might utilize computer-based vocational guidance systems, or occupational simulation kits (Krumboltz 1971).

Biochemical factors influence personality, and the effects of their balance or imbalance on mood and behaviour are found in the personality changes attendant on menstruation. In the last 25 years a great deal of work has been done on the adrenal catecholamines, epinephrine and norepinephrine and other biogenic amines. These compounds have been related to the experiencing of fear, anger and depression (Barchas et al. 1971).

The most commonly used psychological assessment devices are:

• Eysenck Personality Inventory and Mardsley Personality Inventory
• Gordon Personal Profile
• IPAT Anxiety Scale Questionnaire
• Study of Values
• Holland Vocational Preference Inventory
• Minnesota Vocational Interest Test
• Rorschach Inkblot Test
• Thematic Apperception Test

A discussion of burnout would not be complete without a brief overview of the changing family-work system. Shellenberger, Hoffman and Gerson (1994) indicated that “Families are struggling to survive in an increasingly complex and bewildering world. With more choices than they can consider, people are struggling to find the right balance between work, play, love and family responsibility.”

Concomitantly, women’s work roles are expanding, and over 90% of women in the US cite work as a source of identity and self-worth. In addition to the shifting roles of men and women, the preservation of two incomes sometimes requires changes in living arrangements, including moving for a job, long-distance commuting or establishing separate residences. All of these factors can put a great strain on a relationship and on work.

Solutions to offer to diminish burnout and stress on an individual level are:

• Learn to balance your life.
• Share your thoughts and communicate your concerns.
• Limit alcohol intake.
• Re-evaluate personal attitudes.
• Learn to set priorities.
• Develop interests outside of work.
• Do volunteer work.
• Re-evaluate your need for perfectionism.
• Learn to delegate and ask for assistance.
• Take time off.
• Exercise, and eat nutritional meals.
• Learn to take yourself less seriously.

On a larger scale, it is imperative that government and corporations accommodate to family needs. To reduce or diminish stress in the family-work system will require a significant reconfiguration of the entire structure of work and family life. “A more equitable arrangement in gender relationships and the possible sequencing of work and non-work over the life span with parental leaves of absence and sabbaticals from work becoming common occurrences” (Shellenberger, Hoffman and Gerson 1994).

As indicated by Entin (1994), increased differentiation of self, whether in a family or corporation, has important ramifications in reducing stress, anxiety and burnout.

Individuals need to be more in control of their own lives and take responsibility for their actions; and both individuals and corporations need to re-examine their value systems. Dramatic shifts need to take place. If we do not heed the statistics, then most assuredly burnout and stress will continue to remain the significant problem it has become for all society.

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Circulating Red Blood Cells

Interference in haemoglobin oxygen deliverythrough alteration of haeme

The major function of the red cell is to deliver oxygen to the tissue and to remove carbon dioxide. The binding of oxygen in the lung and its release as needed at the tissue level depends upon a carefully balanced series of physicochemical reactions. The result is a complex dissociation curve which serves in a healthy individual to maximally saturate the red cell with oxygen under standard atmospheric conditions, and to release this oxygen to the tissues based upon oxygen level, pH and other indicators of metabolic activity. Delivery of oxygen also depends upon the flow rate of oxygenated red cells, a function of viscosity and of vascular integrity. Within the range of the normal haematocrit (the volume of packed red cells), the balance is such that any decrease in blood count is offset by the decrease in viscosity, allowing improved flow. A decrease in oxygen delivery to the extent that someone is symptomatic is usually not observed until the haematocrit is down to 30% or less; conversely, an increase in haematocrit above the normal range, as seen in polycythaemia, may decrease oxygen delivery due to the effects of increased viscosity on blood flow. An exception is iron deficiency, in which symptoms of weakness and lassitude appear, primarily due to the lack of iron rather than to any associated anaemia (Beutler, Larsh and Gurney 1960).

Carbon monoxide is a ubiquitous gas which can have severe, possibly fatal, effects on the ability of haemoglobin to transport oxygen. Carbon monoxide is discussed in detail in the chemicals section of this Encyclopaedia.

Methaemoglobin-producing compounds. Methaemoglobin is another form of haemoglobin that is incapable of delivering oxygen to the tissues. In haemoglobin, the iron atom at the centre of the haeme portion of the molecule must be in its chemically reduced ferrous state in order to participate in the transport of oxygen. A certain amount of the iron in haemoglobin is continuously oxidized to its ferric state. Thus, approximately 0.5% of total haemoglobin in the blood is methaemoglobin, which is the chemically oxidized form of haemoglobin that cannot transport oxygen. An NADH-dependent enzyme, methaemoglobin reductase, reduces ferric iron back to ferrous haemoglobin.

A number of chemicals in the workplace can induce levels of methaemoglobin that are clinically significant, as for example in industries using aniline dyes. Other chemicals that have been found frequently to cause methaemoglobinaemia in the workplace are nitrobenzenes, other organic and inorganic nitrates and nitrites, hydrazines and a variety of quinones (Kiese 1974). Some of these chemicals are listed in Table 1 and are discussed in more detail in the chemicals section of this Encyclopaedia. Cyanosis, confusion and other signs of hypoxia are the usual symptoms of methaemoglobinaemia. Individuals who are chronically exposed to such chemicals may have blueness of the lips when methaemoglobin levels are approximately 10% or greater. They may have no other overt effects. The blood has a characteristic chocolate brown colour with methaemoglobinaemia. Treatment consists of avoiding further exposure. Significant symptoms may be present, usually at methaemoglobin levels greater than 40%. Therapy with methylene blue or ascorbic acid can accelerate reduction of the methaemoglobin level. Individuals with glucose-6-phosphate dehydrogenase deficiency may have accelerated haemolysis when treated with methylene blue (see below for discussion of glucose-6-phosphate dehydrogenase deficiency).

There are inherited disorders leading to persistent methaemoglobinaemia, either due to heterozygosity for an abnormal haemoglobin, or to homozygosity for deficiency of red cell NADH-dependent methaemoglobin reductase. Individuals who are heterozygous for this enzyme deficiency will not be able to decrease elevated methaemoglobin levels caused by chemical exposures as rapidly as will individuals with normal enzyme levels.

In addition to oxidizing the iron component of haemoglobin, many of the chemicals causing methaemoglobinaemia, or their metabolites, are also relatively non-specific oxidizing agents, which at high levels can cause a Heinz-body haemolytic anaemia. This process is characterized by oxidative denaturation of haemoglobin, leading to the formation of punctate membrane-bound red cell inclusions known as Heinz bodies, which can be identified with special stains. Oxidative damage to the red cell membrane also occurs. While this may lead to significant haemolysis, the compounds listed in Table 1 primarily produce their adverse effects through the formation of methaemoglobin, which may be life threatening, rather than through haemolysis, which is usually a limited process.

In essence, two different red cell defence pathways are involved: (1)  the  NADH-dependent  methaemoglobin  reductase  required to reduce methaemoglobin to normal haemoglobin; and (2) the NADPH-dependent process through the hexose monophosphate (HMP) shunt, leading to the maintenance of reduced glutathione as  a  means  to  defend  against  oxidizing  species  capable  of producing Heinz-body haemolytic anaemia (figure 1). Heinz-body haemolysis can be exacerbated by the treatment of methaemoglobinaemic patients with methylene blue because it requires NADPH for its methaemoglobin-reducing effects. Haemolysis will also be a more prominent part of the clinical picture in individuals with (1)deficiencies in one of the enzymes of the NADPH oxidant defence pathway, or (2) an inherited unstable haemoglobin. Except for the glucose-6-phosphate dehydrogenase (G6PD) deficiency, described later in this chapter, these are relatively rare disorders.

Figure 1. Red blood cell enzymes of oxidant defence and related reactions

GSH + GSH + (O) ←-Glutathione peroxidase-→ GSSG + H₂O

GSSG + 2NADPH ←-Glutathione peroxidase-→ 2GSH + 2NADP

Glucose-6-Phosphate + NADP ←-G6PD-→ 6-Phosphogluconate + NADPH

Fe+++·Haemoglobin (Methaemoglobin) + NADH ←-Methaemoglobin reductase-→ Fe++·Haemoglobin

Another form of haemoglobin alteration produced by oxidizing agents is a denatured species known as sulphaemoglobin. This irreversible product can be detected in the blood of individuals with significant methaemoglobinaemia produced by oxidant chemicals. Sulphaemoglobin is the name also given, and more appropriately, to a specific product formed during hydrogen sulphide poisoning.

Haemolytic agents: There are a variety of haemolytic agents in the workplace. For many the toxicity of concern is methaemoglobinaemia. Other haemolytic agents include naphthalene and its derivatives. In addition, certain metals, such as copper, and organometals, such as tributyl tin, will shorten red cell survival, at least in animal models. Mild haemolysis can also occur during traumatic physical exertion (march haemoglobinuria); a more modern observation is elevated white blood counts with prolonged exertion (jogger’s leucocytosis). The most important of the metals that affects red cell formation and survival in workers is lead, described in detail in the chemicals section of this Encyclopaedia.

Arsine: The normal red blood cell survives in the circulation for 120 days. Shortening of this survival can lead to anaemia if not compensated by an increase in red cell production by the bone marrow. There are essentially two types of haemolysis: (1) intravascular haemolysis, in which there is an immediate release of haemoglobin within the circulation; and (2) extravascular haemolysis, in which red cells are destroyed within the spleen or the liver.

One of the most potent intravascular haemolysins is arsine gas (AsH₃). Inhalation of a relatively small amount of this agent leads to swelling and eventual bursting of red blood cells within the circulation. It may be difficult to detect the causal relation of workplace arsine exposure to an acute haemolytic episode (Fowler and Wiessberg 1974). This is partly because there is frequently a delay between exposure and onset of symptoms, but primarily because the source of exposure is often not evident. Arsine gas is made and used commercially, often now in the electronics industry. However, most of the published reports of acute haemolytic episodes have been through the unexpected liberation of arsine gas as an unwanted by-product of an industrial process—for example, if acid is added to a container made of arsenic-contaminated metal. Any process that chemically reduces arsenic, such as acidification, can lead to the liberation of arsine gas. As arsenic can be a contaminant of many metals and organic materials, such as coal, arsine exposure can often be unexpected. Stibine, the hydride of antimony, appears to produce a haemolytic effect similar to arsine.

Death can occur directly due to complete loss of red blood cells. (A haematocrit of zero has been reported.) However, a major concern at arsine levels less than those producing complete haemolysis is acute renal failure due to the massive release of haemoglobin within the circulation. At much higher levels, arsine may produce acute pulmonary oedema and possibly direct renal effects. Hypotension may accompany the acute episode. There is usually a delay of at least a few hours between inhalation of arsine and the onset of symptoms. In addition to red urine due to haemoglobinuria, the patient will frequently complain of abdominal pain and nausea, symptoms that occur concomitantly with acute intravascular haemolysis from a number of causes (Neilsen 1969).

Treatment is aimed at maintenance of renal perfusion and transfusion of normal blood. As the circulating red cells affected by arsine appear to some extent to be doomed to intravascular haemolysis, an exchange transfusion in which arsine-exposed red cells are replaced by unexposed cells would appear to be optimal therapy. As in severe life-threatening haemorrhage, it is important that replacement red cells have adequate 2,3-diphosphoglyceric acid (DPG) levels so as to be able to deliver oxygen to the tissue.

Other Haematological Disorders

White blood cells

There are a variety of drugs, such as propylthiourea (PTU), which are known to affect the production or survival of circulating polymorphonuclear leucocytes relatively selectively. In contrast, non-specific bone marrow toxins affect the precursors of red cells and platelets as well. Workers engaged in the preparation or administration of such drugs should be considered at risk. There is one report of complete granulocytopenia in a worker poisoned with dinitrophenol. Alteration in lymphocyte number and function, and particularly of subtype distribution, is receiving more attention as a possible subtle mechanism of effects due to a variety of chemicals in the workplace or general environment, particularly chlorinated hydrocarbons, dioxins and related compounds. Validation of the health implications of such changes is required.

Coagulation

Similar to leucopenia, there are many drugs that selectively decrease the production or survival of circulating platelets, which could be a problem in workers involved in the preparation or administration of such agents. Otherwise, there are only scattered reports of thrombocytopenia in workers. One study implicates toluene diisocyanate (TDI) as a cause of thrombocytopenic purpura. Abnormalities in the various blood factors involved in coagulation are not generally noted as a consequence of work. Individuals with pre-existing coagulation abnormalities, such as haemophilia, often have difficulty entering the workforce. However, although a carefully considered exclusion from a few selected jobs is reasonable, such individuals are usually capable of normal functioning at work.

Haematological Screening and Surveillance in the Workplace

Markers of susceptibility

Due in part to the ease in obtaining samples, more is known about inherited variations in human blood components than for those in any other organ. Extensive studies sparked by recognition of familial anaemias have led to fundamental knowledge concerning the structural and functional implications of genetic alterations. Of pertinence to occupational health are those inherited variations that might lead to an increased susceptibility to workplace hazards. There are a number of such testable variations that have been considered or actually used for the screening of workers. The rapid increase in knowledge concerning human genetics makes it a certainty that we will have a better understanding of the inherited basis of variation in human response, and we will be more capable of predicting the extent of individual susceptibility through laboratory tests.

Before discussing the potential value of currently available susceptibility markers, the major ethical considerations in the use of such tests in workers should be emphasized. It has been questioned whether such tests favour exclusion of workers from a site rather than a focus on improving the worksite for the benefit of the workers. At the very least, before embarking on the use of a susceptibility marker at a workplace, the goals of the testing and consequences of the findings must be clear to all parties.

The two markers of haematological susceptibility for which screening has taken place most frequently are sickle cell trait and G6PD deficiency. The former is at most of marginal value in rare situations, and the latter is of no value whatsoever in most of the situations for which it has been advocated (Goldstein, Amoruso and Witz 1985).

Sickle cell disease, in which there is homozygosity for haemoglobin S (HbS), is a fairly common disorder among individuals of African descent. It is a relatively severe disease that often, but not always, precludes entering the workforce. The HbS gene may be inherited with other genes, such as HbC, which may reduce the severity of its effects. The basic defect in individuals with sickle cell disease is the polymerization of HbS, leading to microinfarction. Microinfarction can occur in episodes, known as sickle cell crises, and can be precipitated by external factors, particularly those leading to hypoxia and, to a lesser extent, dehydration. With a reasonably wide variation in the clinical course and well-being of those with sickle cell disease, employment evaluation should focus on the individual case history. Jobs that have the possibility of hypoxic exposures, such as those requiring frequent air travel, or those with a likelihood of significant dehydration, are not appropriate.

Much more common than sickle cell disease is sickle cell trait, the heterozygous condition in which there is inheritance of one gene for HbS and one for HbA. Individuals with this genetic pattern have been reported to undergo sickle cell crisis under extreme conditions of hypoxia. Some consideration has been given to excluding individuals with sickle cell trait from workplaces where hypoxia is a common risk, probably limited to the jobs on military aircraft or submarines, and perhaps on commercial aircraft. However, it must be emphasized that individuals with sickle cell trait do very well in almost every other situation. For example, athletes with sickle cell trait had no adverse effects from competing at the altitude of Mexico City (2,200m, or 7,200ft) during the 1968 Summer Olympics. Accordingly, with the few exceptions described above, there is no reason to consider exclusion or modification of work schedules for those with sickle cell trait.

Another common genetic variant of a red blood cell component is the A^– form of G6PD deficiency. It is inherited on the X chromosome as a sex-linked recessive gene and is present in approximately one in seven Black males and one in 50 Black females in the United States. In Africa, the gene is particularly prevalent in areas of high malaria risk. As with sickle cell trait, G6PD deficiency provides a protective advantage against malaria. Under usual circumstances, individuals with this form of G6PD deficiency have red blood counts and indices within the normal range. However, due to the inability to regenerate reduced glutathione, their red blood cells are susceptible to haemolysis following ingestion of oxidant drugs and in certain disease states. This susceptibility to oxidizing agents has led to workplace screening on the erroneous assumption that individuals with the common A^– variant of G6PD deficiency will be at risk from the inhalation of oxidant gases. In fact, it would require exposure to levels many times higher than the levels at which such gases would cause fatal pulmonary oedema before the red cells of G6PD-deficient individuals would receive oxidant stress sufficient to be of concern (Goldstein, Amoruso and Witz 1985). G6PD deficiency will increase the likelihood of overt Heinz-body haemolysis in individuals exposed to aniline dyes and other methaemoglobin-provoking agents (Table 1), but in these cases the primary clinical problem remains the life-threatening methaemoglobinaemia. While knowledge of G6PD status might be useful in such cases, primarily to guide therapy, this knowledge should not be used to exclude workers from the workplace.

There are many other forms of familial G6PD deficiency, all far less common then the A^– variant (Beutler 1990). Certain of these variants, particularly in individuals from the Mediterranean basin and Central Asia, have much lower levels of G6PD activity in their red blood cells. Consequently the affected individual can be severely compromised by ongoing haemolytic anaemia. Deficiencies in other enzymes active in defence against oxidants have also been reported as have unstable haemoglobins that render the red cell more susceptible to oxidant stress in the same manner as in G6PD deficiency.

Surveillance

Surveillance differs substantially from clinical testing in both the evaluation of ill patients and the regular screening of presumably healthy individuals. In an appropriately designed surveillance programme, the aim is to prevent overt disease by picking up subtle early changes through the use of laboratory testing. Therefore, a slightly abnormal finding should automatically trigger a response—or at least a thorough review—by physicians.

In the initial review of haematological surveillance data in a workforce potentially exposed to a haematotoxin such as benzene, there are two major approaches that are particularly helpful in distinguishing false positives. The first is the degree of the difference from normal. As the count gets further removed from the normal range, there is a rapid drop-off in the likelihood that it represents just a statistical anomaly. Second, one should take advantage of the totality of data for that individual, including normal values, keeping in mind the wide range of effects produced by benzene. For example, there is a much greater probability of a benzene effect if a slightly low platelet count is accompanied by a low-normal white blood cell count, a low-normal red cell count, and a high-normal red cell mean corpuscular volume (MCV). Conversely, the relevance of this same platelet count to benzene haematotoxicity can be discounted if the other blood counts are at the opposite end of the normal spectrum. These same two considerations can be used in judging whether the individual should be removed from the workforce while awaiting further testing and whether the additional testing should consist only of a repeat complete blood count (CBC).

If there is any doubt as to the cause of the low count, the entire CBC should be repeated. If the low count is due to laboratory variability or some short-term biological variability within the individual, it is less likely that the blood count will again be low. Comparison with preplacement or other available blood counts should help distinguish those individuals who have an inherent tendency to be on the lower end of the distribution. Detection of an individual worker with an effect due to a haematological toxin should be considered a sentinel health event, prompting careful investigation of working conditions and of co-workers (Goldstein 1988).

The wide range in normal laboratory values for blood counts can present an even greater challenge since there can be a substantial effect while counts are still within the normal range. For example, it is possible that a worker exposed to benzene or ionizing radiation may have a fall in haematocrit from 50 to 40%, a fall in the white blood cell count from 10,000 to 5,000 per cubic millimetre and a fall in the platelet count from 350,000 to 150,000 per cubic millimetre—that is, more than a 50% decrease in platelets; yet all these values are within the “normal” range of blood counts. Accordingly, a surveillance programme that looks solely at “abnormal” blood counts may miss significant effects. Therefore, blood counts that decrease over time while staying in the normal range need particular attention.

Another challenging problem in workplace surveillance is the detection of a slight decrease in the mean blood count of an entire exposed population—for example, a decrease in mean white blood cell count from 7,500 to 7,000 per cubic millimetre because of a widespread exposure to benzene or ionizing radiation. Detection and appropriate evaluation of any such observation requires meticulous attention to standardization of laboratory test procedures, the availability of an appropriate control group and careful statistical analysis.

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