Platelet function and clotting parameters of vibration-exposed foundry workers.

Platelet function and clotting parameters of vibration-exposed foundry workers. Scand j work environ health 9 (1983) 347-352. Platelet aggregation and blood clotting parameters were studied in 22 workers (84 %) using pneumatic riveting and grinding hand tools and in 20 workers (90 %) not exposed to vibration but comparable with respect to age, anthropo- metric data, smoking and drinking habits, and atherogenic risk factors. The weighted acceleration levels of the vibrating tools are reported. According to Taylor's grading system for vibration-induced white fingers, 15 exposed workers (57 %) were in stage C+, 9 (34 %) in stage ON, and 1 (4 %) in stage 1. Between the reference and the vibration- exposed groups no differences in the platelet aggregation indices both "in vitro" (adenosine-diphosphate, epinephrine, threshold adenosine-diphosphate concentration) and "in vivo" (platelet factor four, beta-thromboglobulin) were found. In addition the clotting parameters (prothrombin index, activated partial thromboplastin time, fibrino- gen, antithrombin 111) and the immunoglobulins G, A, and M were normal in the two groups. The measurement of skin temperature of the third right finger before and after the cold provocation test showed that the vibration exposed workers experienced a stronger vasoconstriction of the digital vessels than the referents. It is concluded that, in the early stages of vasospastic disorders, segmental vibration can induce peripheral vascular hyperreactivity without changes in the platelet function and clotting parameters.

The pathogenic mechanism of the peripheral vasospastic syndrome in workers using handheld vibrating tools is still not fully known. Soviet authors (3) have emphasized the role of an increased vasoconstrictor tone due to the functional sympathetic hyperactivity induced by handarm vibration.
Pyykko (14) considers that the repeated spasms of the digital arteries provoked by vibration give rise to hypertrophy of the medial vessel wall with a concurrent reduction of blood flow. An appropriate vasomotor stimulation, for instance, exposure to cold, is thus able to trigger acute local ischemia. Nerem (10) has noted that the enhancement of shear stress on the arterial wall by segmental vibration of a specific amplitude and frequency can result in endothelial damage; it also affects the arterial wall uptake of proteins and lipids. According to the author, there is a relationship between endothelial damage and Raynaud's phenomenon of occupational origin.
Okada et a1 (12) have investigated the role of biochemical factors in the pathogenesis of vasospastic disease in two groups of chain-saw workers, one with Raynaud's phenomenon and one without. Haptoglobulin (a component of alpha, globulin) and immunoglobulin (Ig) M were found to be increased inlthe group with Raynaud's syndrome. The authors believe that an immunologic response might be the cause of the vascular disorders.
It is well known that blood coagulation is altered in patients with secondary Raynaud's phenomenon caused by other clinical conditions, as connective-tissue dis-eases (sclerodema, systemic lupus erythernatosus, etc). Studies on blood coagulation parameters of users of vibrating tools have given contrasting results.
In vibration workers with Raynaud's phenomenon, Sroczynski et a1 (15) found increased fibrinogen and a shortened duration of 'plasma recalcination. On the contrary, hypocoagulability (prolonged Howell time and increased r and k time of the thromboelastograrn) has been reported for Italian miners examined by Zedda et al (18).
Recently Ikehata et a1 (5) found a hyperaggregability of platelets and an increase in factor VIII-RA and the von Willebrand factor in 42 patients exposed to chain-saw and rockdrill vibration. The aim of the present paper was to determine whether early alterations of platelet function and blood coagulation parameters are detectable in workers exposed for a short time to high vibration levels of pneumatic ort table tools.

Subjects and medical procedures
Forty-eight men working in the trimming station of a large cast-iron foundry were examined. Twenty-six workers were exposed to hand-arm vibration produced by a riveting hammer (Consolidated Pneumatic Tool C Ltd, 7.3 kg, 2 000 blmin) and by a horizontal portable grinder (Ingersoll-Rand, 5.5 kg, 9 000 rlmin). The other 22 workers not exposed to vibration formed the reference group.
Personal health historv. work condi- tions, vibration exposure time, and smoking and alcohol habits were investigated with the use 'of a questionnaire. To estimate the severity of the neurovascular complaints of the fingers and hands, we have adopted the classification proposed by Taylor et a1 (16). A cold provocation test was performed on the exposed and reference groups. The skin temperature was measured by a thermistor at the middle phalanx (dorsal surface) of the third finger of the right hand before immersion in cold water (4°C) for 2 min. The curve of skin temperature recovery of the right third finger was monitored every 3 min for 40 min after the provocation test. The experiments were performed between 1000 and 1200 and the mean room temperature was 22.0 (SD 0.5YC.

Laboratory investigations
Blood samples were obtained from the 48 workers, and the following biochemical parameters were assayed: total and highdensity lipoprotein cholesterol, triglyceride levels, total serum protein, and IgG, IgA and IgM. In 42 subjects (22 exposed and 20 referents) platelet aggregation and coagulation parameters were studied. The blood sarnples were obtained after an overnight fast, 12 h of smoking abstinence, and without venous stasis. Platelet aggregation was performed according to Born's photometric method (1). The blood sample was withdrawn into a plastic syringe containing 2.0 ml of 3.8 % sodium citrate (9 ml of blood to 1 ml of sodium citrate). Plateletrich plasma was prepared by the centrifuging of the citrated blood in plastic tubes at 400 rlmin for 15 min. The supernatant (platelet-rich plasma) was carefully removed and counted in Burker's chamber with a phase-contrast microscope on a 1: 200 dilution of platelet-rich plasma with platelet diluting fluid (Becton, Dickinson & Co, monouse pipette system). Platelet aggregation was determined by a photometric method using an ELVI 840 in conjunction with a Logos Omniscribe TM 176 recorder. The aggregometer was set on the assumption that platelet-poor plasma represents 100 % and platelet-rich plasma represents 0 % aggregation. The tube containing that sample (250 yl) of plateletrich plasma (300-350,000 plateletslmm3) was stirred at a constant speed (1,100 rlmin) and after at least 3 min 10 wl of an adenosinediphosphate (ADP) or epinephrine solution was then added to give a final concentration of 0.8, 1.2, 2.0 x 10-6 M (ADP) and 4.0 x 10-6 M (epinephrine). The results were expressed following Yamazaki's criteria (18).
Beta-thromboglobulin levels were assayed utilizing the Amersham Ria Kit. The blood samples, drawn with the evacuated blood collection tubes (Abbott) (4) containing 2.5 % ethylenediaminetetraacetate, 0.0025 % chloradenosine and 7 % procainehydrochloric acid, were placed in ice water for 30 min before spinning at 2,000 rlmin for 40 min. The top was removed and stored at -70°C until the assay, as described by Ludlam et al (8). Platelet factor four levels were assayed with the use of the Abbott Ria Kit. The collection and the preparation of the samples were the same as previously described for beta-thromboglobulin. Antithrombin III was determined by chromogenic substrate (Abbott Kit) (1 1). Platelet count, activated partial thromboplastin time (131, one-step prothrombin time (expressed as the prothrombin index), and fibrinogen were also determined.
The measurement of all the parameters expressed as clotting time after recalcification were performed by a semi-automatic instrument which measured the coagulation time (s) of the plasma by the modification of its optical density (Fibrintimer Labor).
The statistical evaluation of the results (Student's t-test, chi-square test) was performed with a personal computer (Apple 11).

Vibration measurements
The one-third octave band frequency spectra of the acceleration levels of the tools used by the foundry workers were measured. The characteristics of the recording and analysis equipment (Bruel & Kjaer) and the engineering data have been discussed elsewhere (2). In this paper we report the root-mean-square weighted acceleration levels of the tools (a, in m/s2, 8-1,000 Hz), computed by the procedure recommended by the International Organization for Standardization (6).

Results
The exposure time of workers using vibrating tools ranged from 1 to 12 years (mean 5.5 years, SD 3.4 years). The mean estimated work time was 2.4 h of riveting and 1.1 h of grinding.
The weighted acceleration sum (X, Y, Z axes) was 42.1 mls2 at the handle and 168.1 mls2 at the barrel of the riveting hammer, and the weighted acceleration level of the grinder was 8.9 mls2.
According to the stage assessment of vibration-induced white fingers developed by Taylor et a1 (16), the following prevalence of neurovascular complaints of the fingers of the exposed group was found: 1 subject (4 %) had no symptoms (stage 0); tingling (stage 4 . 3 and numbness (stage ON) were experienced by 15 (57 %) and 9 (34 %) workers, respectively; 1 man (4 5%) suffered from Raynaud's phenomenon (stage 1). In the reference group only two workers (9 7%) were affected with paresthesia in the upper extremities.
In table 1 the characteristics of vibrationexposed workers and the referents are reported. The two groups were comparable with respect to age and anthropometric parameters. The exposed workers smoked more cigarettes and drank more alcohol than the referents, but the differences were not significant. In addition risk factors for atherosclerosis (systolic and diastolic arterial pressure, total and high density lipoprotein cholesterol, triglycerides) were similar in the two groups.
The basal skin temperature values of the third right finger were 32.2 (SD 2.3YC in the exposed workers and 33.5 (SD 1.4)"C in the referents (p = 0.03). Fig 1 shows that Table 1. Characteristics of the vibration-exposed workers and the referents.  Platelet aggregation indices and clotting parameters of the vibration-exposed workers and the referents. there was a marked difference in the cumulative percentage rates of the vibration exposed and reference workers' recovery of the basal skin temperature after the cold provocation test. In table 2 the mean values and standard deviations of the parameters which explore the platelet and coagulation functions are reported. Platelet count and the indices of platelet aggregation "in vitro" (ADP, epinephrine, threshold ADP concentration) were not significantly different Table 3. Total serum protein and immunoglobulins (lg) in the vibration-exposed workers and the referents. in comparison with those of the referents. Between the two groups no abnormalities were found in the blood levels of platelet factor four and beta-thromboglobulin, which are proteins contained in the platelet alpha granules and secreted during the release reaction. The values of clotting parameters such as the prothrombin index, activated partial thromboplastin time, fibrinogen, and antithrombin I11 were similar for the vibration and reference workers.

Exposed workers Referents
Total serum protein and the immunoglobulins IgG, IgA, IgM were normal in both groups (table 3).

Discussion
The results of this study suggest that workers exposed to vibration from handheld tools show an intense and longlasting peripheral vasoconstriction after a cold provocation test, even if they are not affected with Raynaud's phenomenon. In the vibration group, 20 men (76 %) did not recover their basal skin temperature during the first 40 min which followed the local cooling, while rewarming of the finger of 20 referents (91 %) occurred within 21 min. This result means that in the vibrationexposed workers the cold stimulation gave rise to a stronger luminal reduction of the digital vessels than in subjects who were not exposed to vibration but were comparable with respect to age, anthropometric data, smoking and drinking habits, and atherogenic factors.
Our laboratory data reveal that the platelet and coagulation functions were not altered in the exposed wqrkers. Between the vibration and reference groups there was no difference in the platelet aggregation indices both "in vitro" (ADP, epinephrine, threshold ADP concentration) and "in vivo" (platelet factor four, betathromboglobulin). The clotting parameters were also normal. The norrnocoagulability of both groups is well denoted by the antithrombin I11 level, which is a good index of coagulation "in vivo." It is difficult to compare these results with those reported by other authors (5,15,19) because they refer to different stages of Raynaud7s syndrome. However our findings suggest that, at least in the early stages of vasospastic disease, segmental vibration does not induce endothelial damage, which is one of the most potent activators of platelet aggregation.
According to Knutsson (7) the serum levels of IgG, IgA, and IgM in exposed workers were not significantly raised as compared with referents. This finding contrasts with Okada's immunologic hypothesis for the vasospastic reaction (12). In conclusion hand-arm vibration, alone or in combination with other stimuli such as cold, noise, and ergonomic conditions, can elicit an abnormal vasoconstrictor response of the digital vessels (14,17). In workers exposed for a short time to high vibration levels, we have found peripheral vascular hyperreactivity that occurs without abnormalities in platelet aggregation and clotting parameters. Other pathogenic factors for the digital ischemia have to be taken into account however, factors such as excessive sympathetic activity (3) or hernodynamic local changes (9).
Nevertheless the results of our study do not exclude the possibility that, in subjects with more severe vibration-induced white fingers (stage 2 or 3), hemostatic disorders could play a role in the pathogenesis of Raynaud's phenomenon of occupational origin (5,15).