Exposição humana ao mercúrio e seus efeitos hematológicos: uma revisão sistemática

Vianna, Angélica dos Santos; Matos, Elisabete Pedra de; Jesus, Iracina Maura de; Asmus, Carmen Ildes Rodrigues Fróes; Câmara, Volney de Magalhães

doi:10.1590/0102-311X00091618

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REVIEW • Cad. Saúde Pública 35 (2) • 2019 • https://doi.org/10.1590/0102-311X00091618 linkcopiar

Exposição humana ao mercúrio e seus efeitos hematológicos: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

O mercúrio é um metal que pode ser encontrado naturalmente no meio ambiente e através de fontes antropogênicas. É altamente tóxico para ecossistemas e seres vivos. A maior parte da exposição humana provém da ingestão de pescados contaminados, da liberação de gases da amálgama dentária ou da exposição ocupacional (p.ex.: extração de ouro). Vastas populações são expostas ao mercúrio, tornando-se uma questão de saúde pública muito importante. Efeitos adversos à saúde são comumente observados no sistema nervoso, mas todos os órgãos são alvos em potencial, como a medula óssea. O principal objetivo do estudo foi avaliar as evidências disponíveis sobre a exposição humana ao mercúrio e seus efeitos hematológicos. Uma estratégia de busca foi realizada, incluindo termos chave (palavras-chave, palavras do texto e equivalentes), para pesquisar dois repositórios de dissertações de mestrado e teses de doutorado (Fiocruz/ARCA e Universidade de São Paulo) e quatro bases de dados eletrônicas: BVS/LILACS, MEDLINE/PubMed, Scopus e TOXLINE/NIH (artigos publicados de 1950 até fevereiro de 2018). Não houve restrições de linguagem e uma ferramenta (EPHPP) foi utilizada para avaliar a qualidade dos estudos incluídos. De acordo com os critérios pré-estabelecidos, foram encontrados 80 estudos, todos observacionais (48 relatos de caso, 24 estudos transversais, 6 séries de casos e 2 coortes), que compreendiam 9.284 pessoas. Apesar do fato de que as pessoas mais expostas (6.012) tinham contagens de células sanguíneas normais, e os efeitos hematológicos do mercúrio não pareciam muito comuns (1.914 casos, 14 graves e 29 mortes), três estudos relataram a associação de (β) anemia, linfopenia, neutrofilia e basofilia. Concluímos que as informações coletadas indicam efeitos hematotóxicos do mercúrio, alguns dos quais podem ser muito graves e até fatais.

Palavras-chave:
Intoxicação por Mercúrio; Intoxicação por Metais Pesados; Mercúrio; Contagem de Células Sanguíneas

Hematological effect	Exposure	Cases
Anemia	Non-occupational	547
Anemia	Occupational	328
Polycythemia	Non-occupational	0
Polycythemia	Occupational	48
Leukopenia	Non-occupational	84
Leukopenia	Occupational	22
Leukocytosis	Non-occupational	23
Leukocytosis	Occupational	3
Basopenia	Non-occupational	80
Basopenia	Occupational	0
Basophilia	Non-occupational	191
Basophilia	Occupational	0
Eosinophilia	Non-occupational	30
Eosinophilia	Occupational	7
Neutropenia	Non-occupational	26
Neutropenia	Occupational	0
Neutrophilia	Non-occupational	199
Neutrophilia	Occupational	5
Lymphopenia	Non-occupational	273
Lymphopenia	Occupational	33
Lymphocytosis	Non-occupational	102
Lymphocytosis	Occupational	259
Monocytopenia	Non-occupational	56
Monocytopenia	Occupational	0
Monocytosis	Non-occupational	24
Monocytosis	Occupational	0
Thrombocytopenia	Non-occupational	19
Thrombocytopenia	Occupational	2
Thrombocytosis	Non-occupational	2
Thrombocytosis	Occupational	0
Pancytopenia	Non-occupational	5
Pancytopenia	Occupational	1
Other (alteration of hematocrit and leukocytes)	Non-occupational	0
Other (alteration of hematocrit and leukocytes)	Occupational	7
Total		2,376

Study (year)	Country	Study characteristics [design/number/exposure]	Population [age/sex]	Mercury level	Hemtologic effect	Statistical analysis	EPHPP tool
Bender et al. ²⁷ (1950)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Female (61y)	NI	Anemia = 1, leukopenia = 1, neutropenia = 1	NA	3
Butt & Simonsen ⁴¹ (1950)	USA	Cross-sectional; n = 134, no control (occupational = 1, non-occupational = 55, NI = 78); non-occupational (medicine + environment + maternal exposure)	Female = 22, male = 42, NI = 69 (< 1-81y)	High	Thrombocytopenia = 12	ND	3
Doolan et al. ⁷³ (1953)	USA	Case report; n = 1; non-occupational (suicide)/chronic	Female (28y)	NI	Anemia = 1	NA	3
Portwich & Maron ²⁸ (1959)	Germany	Case report; n = 1; non-occupational (medicine)/chronic	Female (64y)	NI	Thrombocytopenia = 1	NA	3
Larsen et al. ⁸² (1963)	USA	Case report; n = 2; non-occupational (medicine)/acute	Female = 1, male = 1 (55y, 69y)	NI	Leukocytosis = 1, normal = 1	NA	3
Ross ⁸³ (1964)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Male (4y)	High	Leukocytosis = 1	NA	3
Wilson ²⁹ (1966)	UK	Case report; n = 1; non-occupational (medicine)/chronic	Male (77y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Johnson et al. ³⁰ (1978)	USA	Case report; n = 1; non-occupational (medicine)/chronic	Female (3y)	High	Anemia = 1, leukopenia = 1, neutropenia = 1	NA	3
Hannigan ⁸⁴ (1978)	UK	Case report; n = 1; non-occupational (suicide)/chronic	Male (34y)	High	Normal = 1	NA	3
Murphy et al. ³¹ (1979)	UK	Case report; n = 1; non-occupational (medicine)/acute	Male (35y)	High	Anemia = 1, leukocytosis = 1, neutrophilia = 1, thrombocytopenia = 1	NA	3
Slee et al. ³² (1979)	Netherlands	Case report; n = 1; non-occupational (medicine)/acute	Female (59y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Wright et al. ⁸⁵ (1980)	UK	Case report; n = 1; non-occupational (suicide)/acute	Male (17y)	NI	Normal = 1	NA	3
Lien et al. ⁸⁶ (1983)	Canada	Case series; n = 7 (occupational = 1, non-occupational = 6); non-occupational (home)/acute	Female = 1, male = 2, NI = 3 (< 2-28y)	High = 6	Leukocytosis = 6	NA	3
McNeil et al. ⁸⁷ (1984)	UK	Case series; n = 4; non-occupational (home)/chronic	Female = 2, male = 2 (10-41y)	High	Normal = 4	NA	3
Foulds et al. ⁸⁸ (1987)	USA	Case report; n = 1; non-occupational (home)/chronic	Female (< 3y)	High	Normal = 1	NA	3
Lauwerys et al. ²⁵ (1987)	Belgium	Case report; n = 1; non-occupational (aesthetic/maternal exposure)/chronic	Male (< 1y)	High	Anemia = 1, leukocytosis = 1, lymphocytosis = 1	NA	3
Oliveira et al. ⁸⁹ (1987)	UK	Case report; n = 1; non-occupational (aesthetic)/chronic	Female (46y)	High	Anemia = 1	NA	3
Tunnessen et al. ⁷⁸ (1987)	USA	Case report; n = 1; non-occupational (school)/chronic	Male (< 2y)	High	Leukocytosis = 1, Eosinophilia = 1, thrombocytosis = 1	NA	3
Murray & Hedgepeth ⁹⁰ (1988)	USA	Case report; n = 1; non-occupational (suicide)/chronic	Male (25y)	High	Anemia = 1, neutrophilia = 1	NA	3
Oluwole et al. ⁴² (1989)	Nigeria	Cross-sectional; n = 21 (no control); non-occupational (environment)/chronic	Male = 21 (3-12y)	High = 1, normal = 20	Anemia = 10, normal = 11	t-test, no mean difference, p < 0.05	3
Siblerud ⁴³ (1990)	USA	Cross-sectional; n = 101 (exposed = 50, not exposed = 51); non-occupational (amalgam)/chronic	Female = 60, male = 41 (exposed x = 22y, not exposed x = 23y)	NI	Anemia = 15, normal = 86	Mean difference, p = 0.016; Pearson r = -0.4208, p = 0.003	3
Montoya-Cabrera et al. ²⁶ (1991)	Mexico	Case report; n = 1; non-occupational (medicine)/acute	Female = 1 (< 1y)	High	Anemia = 1, lymphocytosis = 1	NA	3
Schwartz et al. ⁸¹ (1992)	USA	Case series; n = 4; non-occupational (home)/acute	Female = 1, male = 3 (< 4y-adults)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1, normal = 3	NA	3
Pavithran ³³ (1994)	India	Case report; n = 1; non-occupational (medicine)/chronic	Female (29y)	ND	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Alvarado et al. ³⁴ (1995)	Costa Rica	Case report; n = 2 (occupational = 1, non-occupational = 1); non-occupational (medicine)/chronic	Male (25y)	NI	Leukocytosis = 1, neutrophilia = 1	NA	3
Fuortes et al. ³⁹ (1995)	USA	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (10y, 12y, 17y)	High	Anemia = 1, leukocytosis = 1, eosinophilia = 2, thrombocytopenia = 2, normal = 1	NA	3
Dell’Omo et al. ⁹¹ (1997)	Italy	Case report; n = 1; non-occupational (suicide)/chronic	Male (34y)	High	Normal = 1	NA	3
Dada et al. ³⁵ (1999)	South Africa	Case report; n = 1; non-occupational (medicine)/acute	Male (21y)	NI	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Chodorowski & Anand ⁹² (2000)	Poland	Case report; n = 2; non-occupational (suicide)/acute	Male = 2 (19-59y)	High	Normal = 2	NA	3
Tschanz & Prins ⁷⁷ (2000)	Switzerland	Case report; n = 1; non-occupational (medicine)/acute	Female (29y)	NI	Leukocytosis = 1, eosinophilia = 1	NA	3
González et al. ⁹³ (2001)	Venezuela	Case report; n = 1; non-occupational (medicine)/acute	Female (3y)	Normal	Anemia = 1, leukocytosis = 1, neutrophilia = 1, thrombocytosis = 1	NA	3
Deschamps et al. ⁹⁴ (2002)	France	Case report; n = 1; non-occupational (suicide)/chronic	Male (41y)	High	Normal = 1	NA	3
Langworth et al. ⁹⁵ (2002)	Sweden	Cross-sectional; n = 379 (no control); non-occupational (amalgam)/chronic	Female = 263, male = 116 (x = 46y)	High	Anemia = 6, normal = 373	ND	3
Winkler et al. ⁹⁶ (2002)	Austria	Case report; n = 1; non-occupational (suicide)/acute	Male (22y)	High	Anemia = 1	NA	3
Kouyn et al. ⁹⁷ (2004)	Turkey	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (11y, 13y, 16y)	Normal = 1, high = 2	Normal = 3	NA	3
Glezos et al. ⁹⁸ (2006)	Canada	Case report; n = 1; non-occupational (home)/acute	Male (43y)	High	Anemia = 1	NA	3
Maramba et al. ⁷⁶ (2006)	Philippines	Cross-sectional; n = 140 (exposed = 100, not exposde = 40); non-occupational (gold minig = food)/chronic	Female = 70, NI = 70 (35 < 1y, 35 < 2y, 70 x = 28y)	Normal, high *	Anemia = 140, eosinophilia = ?	ND	3
Frisk et al. ⁴⁶ (2007)	Sweden	Cross-sectional; n = 46 (exposed = 24, not exposed = 22); non-occupational (amalgam)/acute	Adults = 46	Normal	Leukopenia = 24, neutropenia = 24, basopenia = 24, lymphopenia = 24, eosinophilia = 24, monocytosis = 24, normal = 22	Wilcoxon’s sign rank, mean difference, p < 0.05	3
Matushita et al. ⁹⁹ (2007)	Brazil	Case report; n = 1; non-occupational (suicide)/chronic	Male (29y)	High	Normal = 1	NA	3
Bamonti et al. ¹⁰⁰ (2008)	Italy	Case report; n = 1; non-occupational (amalgam)/acute	Female (63y)	Normal	Anemia = 1, leukocytosis = 1, neutrophilia = 1, lymphopenia = 1	NA	3
Girault et al. ¹⁰¹ (2008)	France	Case report; n = 1; non-occupational (medicine)/acute	Female (66y)	High	Neutrophilia = 1, lymphopenia = 1	NA	3
Berrouet Mejía et al. ¹⁰² (2008)	Colombia	Case report; n = 1; non-occupational (suicide)/chronic	Female (16y)	High	Anemia = 1, leukocytosis = 1, neutrophilia = 1	NA	3
De Palma et al. ³⁶ (2008)	Italy	Case report; n = 1; non-occupational (suicide)/acute	Female (30y)	High	Anemia = 1, leukocytosis = 1	NA	3
Erkek et al. ⁴⁰ (2010)	Turkey	Case report; n = 1; non-occupational (environment)/acute	Female (10y)	High	Anemia = 1	NA	3
Sarikaya et al. ¹⁰³ (2010)	Turkey	Case report; n = 1; non-occupational (school)/acute	Female (36y)	NI	Normal = 1	NA	3
Al-Sinani et al. ⁷⁹ (2011)	Oman	Case report; n = 1; non-occupational (medicine)/chronic	Female (12y)	High	Leukocytosis = 1, eosinophilia = 1	NA	3
Plante et al. ⁴⁹ (2011)	Canada	Cross-sectional; n = 466 (no control); non-occupational (food)/chronic	Female = 466 (20-54y)	High	Anemia = 200, normal = 266	Previous data not shown. Pearson r = 0.04, p-value not informed	3
Yildrim et al. ³⁷ (2012)	Turkey	Case series; n = 5; non-occupational (home)/acute	Female = 3, male = 2 (20-54y)	High	Anemia = 2, leukopenia = 2, thrombocytopenia = 2, normal = 2	NA	3
Priya et al. ¹¹ (2012)	India	Case report; n = 1; non-occupational (suicide)/acute	Female (19y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Khoury et al. ¹⁰⁴ (2013)	Brazil	Cross-sectional; n = 157 (exposed = 108, not exposed = 49); non-occupational (gold mining + food)/chronic	NI = 157 (13-53y)	Normal = 49, high = 108	NI	ND	3
Kim et al. ⁵⁰ (2013)	Korea	Cross-sectional; n = 311 (no control); non-occupational (food)/chronic	Female = 141, male = 170 (5-12y)	High = 7	Lymphocytosis = 100, normal = 211	Spearman r = 0.121, p = 0.049	3
Wu et al. ⁷² (2013)	Taiwan	Case report; n = 1; non-occupational (medicine)/acute	Male (51y)	Normal	Anemia = 1	NA	3
Beasley et al. ¹⁰⁵ (2014)	New Zealand	Case report; n = 1; non-occupational (suicide)/acute	Female (19y)	High	Leukocytosis = 1, neutrophilia = 1	NA	3
Brázdová et al. ⁴⁷ (2014)	Kazakhstan, Kyrgyzstan, Uzbeskistan	Cross-sectional; n = 60; non-occupational (environment)/chronic	Female = 27, male = 33 (1-15y)	Normal	Anemia = 60	Bonferroni’s test, mean difference, p < 0.05	3
Dardamanis et al. ¹⁰⁶ (2014)	Greece	Case report; n = 1; non-occupational (thermometer)/acute	Female (48y)	NI	Anemia = 1	NA	3
Cicek-Senturk et al. ¹⁰⁷ (2014)	Turkey	Case report; n = 3; non-occupational (home)/chronic	Female = 1, male = 2 (14y, 52y, NI)	High	Anemia = 1, leukocytosis = 3	NA	3
Mathee et al. ⁴⁸ (2014)	South Africa	Cross-sectional; n = 307 (exposed = 60, not exposed = 247); non-occupational (geophagia)/chronic	Female = 307 (18-46y)	Normal	Anemia = 52, normal = 255	No association (OR not informed), no mean difference, p = 0.183	2
Kim et al. ⁵¹ (2015)	Korea	Cohort; n = 4,350 (no control); non-occupational (food)/chronic	Female = 2,175, male = 2,175 (7y)	High	Basophilia = 191, neutrophilia = 191, lymphopenia = 191, normal = 4,159	Linear mixed model, β = 1.38 (95%CI: 0.11; 2.65)	2
Oulhote et al. ⁵² (2017)	Denmark	Cohort; n = 56 (no control); non-occupational (food)/chronic	Female = 33, male = 22, NI = 1 (7-12y)	Normal, high *	Leukopenia = 56, basopenia = 56, lymphopenia = 56, monocytopenia = 56	Structural equation, β = -0.23 (95%CI: -043; -0.04), p = 0.02	2
Weinhouse et al. ⁵³ (2017)	Peru	Cross-sectional; n = 83 (no control); non-occupational (gold mining + food)/chronic	Female = 44, male = 38, NI = 1 (< 12y)	Normal = 35, high = 48	Anemia = 41, normal = 42	Multivariate linear, regression model, β = -0.14g/dL, p = 0.04	2

Study (year)	Country	Study characteristics [design/number/exposure]	Population [age/sex]	Mercury level	Hemtologic effect	Statistical analysis	EPHHP tool
Butt & Simonsen ⁴¹ (1950)	USA	Cross-sectional; n = 134, no control (occupational = 1, non-occupational = 55, NI = 78); occupational (fur cleaning plant)/chronic	Female (49y)	High	Thrombocytopenia = 1	ND	3
Devlin & Sudlow ¹⁰⁸ (1967)	UK	Case report; n = 1; occupational (laboratory)/chronic	Male (32y)	High	Leukopenia = 1, thrombocytopenia = 1	NA	3
Takamatsu et al. ¹⁰⁹ (1969)	Japan	Case series; n = 5; occupational (agriculture)/chronic	Male = 5 (adults = 5)	High = 5	Leukopenia = 5	NA	3
Ryrie et al. ³⁸ (1970)	UK	Case report; n = 1; occupational (thermometer fabric)/acute	Male (59y)	High	Anemia = 1, leukopenia = 1, thrombocytopenia = 1	NA	3
Gys & Fadeev ⁸⁰ (1971)	USSR	Cross-sectional; n = 103 (no control); occupational (agriculture)/chronic	NI (adults = 103)	ND	Leukopenia = ?	ND	3
Nizov & Shestakov ¹¹⁰ (1971)	USSR	Case series; n = 10; occupational (agriculture)/acute	NI (adults = 10)	ND	Anemia = 10, leukopenia = 10	NA	3
Jung & Aaronson ¹¹¹ (1980)	USA	Case report; n = 1; occupational (gold mining)/acute	Male (53y)	High	Polycythemia = 1; leukocytosis = 1; neutrophilia = 1	NA	3
Lien et al. ⁸⁶ (1983)	Canada	Case series; n = 7 (occupational = 1, non-occupational = 6); occupational (gold mining)/acute	Male = 1 (28y)	High = 1	Leukocytosis = 1	NA	3
Kanamaru et al. ⁷⁵ (1984)	Japan	Cross-sectional; n = 1,164 (no control); occupational (agriculture)/chronic	Female = 397, male = 767 (adults = 1,164)	Female x = 2.97, male x = 5.35	Anemia = 197, normal = 967	ND	3
Langworth et al. ⁴⁴ (1993)	Sweden	Cross-sectional; n = 110 (exposed = 71, not exposed = 39); occupational (chlor-alkali fabric/lamp facgtory/dentist office)/chronic	Female 75, male = 35 (exposed x = 49y, not exposed x = 40y)	Exposed x = 4.3, not exposed x = 3.9	Normal = 110	t-test, no mean difference, Pearson r not informed, no correlation	3
Torresani et al. ¹¹² (1993)	Italy	Case report; n = 1; occupational (agriculture)/chronic	Female (54y)	ND	Eosinophilia = 1	NA	3
Zavariz & Glina ¹³ (1993)	Brazil	Cross-sectional; n = 91 (no control); occupational (lamp fabric)/chronic	Female = 8, male = 83 (20-65y)	High = 54, normal = 32, NI = 42	Anemia = 1, leukopenia = 6, lymphocytosis = 6, eosinophilia = 5, neutrophilia = 4, normal = 69	ND	3
Moszczyński & Slowiński ²² (1994)	Poland	Cross-sectional; n = 91 (exposed = 55, not exposed = 36); occupational (chlor-alkali fabric)/chronic	Male = 91 (28-55y)	High = 55, normal = 36	Lymphocytosis = 55, normal = 36	t-test, no mean difference, Pearson r = 0.3405, p < 0.05	3
Alvarado et al. ³⁴ (1995)	Costa Rica	Case report; n = 2 (occupational = 1, non-occupational = 1); occupational (compressor)/chronic	Male (30y)	High	Normal = 1	NA	3
Moszczyński et al. ²³ (1995)	Poland	Cross-sectional; n = 117 (exposed = 81, not exposed = 36); occupational (chlor-alkali fabric)/chronic	Male = 117 (21-60y)	Exposed x = 54	Lymphocytosis = 81, normal = 36	t-test, no mean difference, Pearson r = -0.11, 0.10, no correlation	3
Queiroz & Dantas ¹² (1997)	Brazil	Cross-sectional; n = 41 (exposed = 33, not exposed = 8); occupational (chlor-alkali fabric)/chronic	NI (19-46y)	Normal = 41	Lymphopenia = 33, normal = 8	Mann-Whitney’s U, mean difference, p < 0.05, Pearson r = -0.077, no correlation	3
Melo et al. ¹¹³ (2000)	Venezuela	Cross-sectional; n = 47 (no control); occupational (dentist office)/chronic	NI	NI	Hemoglobin alteration = 4, leukocyte alteration = 3, normal = 40	ND	3
Zabiński et al. ⁴⁵ (2000)	Poland	Cross-sectional; n = 81 (exposed = 46, not exposed = 35); occupational (chlor-alkali fabric)/chronic	NI (20-56y)	x = 77.44 ± 48.15 (exposed/not exposed)	Polycythemia = 46, normal = 35	t-test, mean difference, 47.89% vs. 46.1%, p < 0.05	3
Soleo et al. ²⁴ (2002)	Italy	Cross-sectional; n = 289 (exposed = 117, not exposed = 172); occupational (lamp fabric)/chronic	NI (adults = 289)	Normal = 289	Lymphocytosis = 117, normal = 172	t-test, no mean difference, Pearson r = 0.184, positive correlation	3
Campbell et al. ⁷⁴ (2009)	UK	Case report; n = 1; occupational (lamp fabric)/acute	Male (25y)	High	Polycythemia = 1	NA	3
Rodríguez et al. ¹¹⁴ (2002)	Spain	Cross-sectional; n = 26 (no control); occupational (gold mining)/chronic	NI	ND	Anemia = 26	NA	3
Alhamad et al. ¹¹⁵ (2011)	USA	Case report; n = 1; occupational (thermometer fabric)/acute	Male = (36y)	High	Leukocytosis = 1, eosinophilia = 1	NA	3
Douine et al. ⁵⁴ (2018)	Guyana/Suriname	Cross-sectional; n = 421 (exposed = 202, not exposed = 219); occupational (gold mining)/chronic	Female = 124, male = 297 (x = 37y)	ND	Anemia = 93, normal = 328	Prevalence 22% (95%CI: 18.0; 25.9)	2

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[TFN1] 95%CI: 95% confidence interval; EPHPP: Effective Public Health Practice Project; NA: not applicable; ND: not done; NI: not informed.

[TFN2] * From normal to high levels of mercury (range).