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Hematologic effects of heavy metal poisoning.

Heavy metal poisoning can cause a variety of hematologic disorders. Exposure to heavy metals is ubiquitous in the industrial environment and must be considered in the differential diagnosis of many types of anemia. The heavy metals most commonly associated with hematologic toxicity are arsenic and its derivative arsine, copper, gold, lead, and zinc. A few distinctive clinical features characterize the hematologic manifestations of many occult heavy metal poisonings. These features have a limited differential diagnosis. A knowledge of these clinical features can assist the astute clinician in making the correct diagnosis.

Anemia↗

Factors involved in heavy metal poisoning.

The heavy metals include at least 40 elements but cadmium, lead, and mercury have been most extensively studied. The biological properties of heavy metals are discussed in terms of three important characteristics: the ability to form, irreversibly, complexes and chelates with organic ligands; the properties to form organic-metallic bonds; and the potential to undergo oxidation-reduction reactions. The formation of complexes and chelates within the body is shown to influence greatly the dynamics of transport, distribution, and excretion of several important metal cations. The excretion of uranium is influenced by acid-base balance in the body because uranium forms complexes with bicarbonate anions that are filtered by the kidneys. The biliary excretion of methylmercury depends on the formation of small molecular weight complexes with sulfur-containing amiono acids and the peptides in the liver. The degree of enterohepatic recirculation of a variety of heavy metals appears to depend on the chemical nature of the bilary complexes. The oxidation of elemental to divalent ionic mercury is the crurial step in the retention and tissue deposition of inhaled mercury vapor. That the oxidation process is, at least in part, catalyzed by the enzyme, catalase, explains the effects of ethanol, aminotriazole and the state of acatalasemia on the metabolism of inhaled vapor in man and animals. The formation of covalent bonds between metal cations and the carbon atom usually greatly modifies the biological properties of the metal. Methylarsenic and methylmercury compounds both differ from the inorganic forms in accumulation in animals.

Animals↗

Use of hair analysis in the diagnosis of heavy metal poisoning: report of three cases.

We report three paediatric cases of suspected heavy metal poisoning that presented with non-specific symptoms. Hair samples of the three patients were sent overseas for analysis; results showed abnormal levels of many elements, including some heavy metals. A diagnosis of heavy metal poisoning was made and chelation therapy was offered to each patient. Blood levels for some heavy metals were subsequently checked and all were within the normal range. The original diagnosis of heavy metal poisoning was therefore not substantiated. The patients did not have a history of exposure to heavy metals or specific clinical features of heavy metal poisoning. The non-invasive nature of hair analysis is tempting, but the validity of such testing in diagnosing heavy metal poisoning is questionable.

Chelation Therapy↗

N-Acetylcysteine therapy of acute heavy metal poisoning in mice.

Therapy of acute heavy metal poisoning is currently limited to a group of moderately toxic drugs containing sulfhydryl groups. N-Acetylcysteine (NAC) was used in these studies to determine if this sulfhydryl containing amino acid would reduce the overall mortality of a group of heavy metal compounds. D-Penicillamine and dimercaprol (BAL) were also used for comparison. Groups of at least 100 mice (28 g) were injected subcutaneously with 2-190 mg/kg of copper, arsenic, thallium or cadmium for LD50 determinations. Other groups were injected 30-60 min later with NAC (200 mg/kg), d-penicillamine (50 mg/kg), or BAL (10 mg/kg), and mortality was monitored for 2 weeks. The LD50 for each treatment group was determined by regression analysis of log-probit transformed data. In arsenite treatment group the survival time was lengthened in NAC-treated animals although the LD50 was not significantly changed. BAL was only slightly more effective than NAC. The mortality in animals given copper and treated with NAC was almost eliminated, except at the highest doses. BAL provided the greatest protection, whereas d-penicillamine produced the least. The LD50 of copper was significantly changed from 60.5 mg/kg in control groups to 139 mg/kg in NAC-treated groups, and to 150 mg/kg and 91 mg/kg in BAL and d-penicillamine-treated groups. NAC and BAL were totally ineffective in the treatment of thallium and cadmium poisoning.

Acetylcysteine↗

2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans.

14 patients with heavy metal poisoning received 2,3-dimercaptosuccinic acid (DMSA). 12 subjects were given 30 mg/kg/day for 5 days; 1 subject was started on a lower dose because of a history of atopy; another subject was treated for 15 days because of very high initial blood lead concentrations. In the 9 subjects who had lead poisoning, DMSA decreased blood lead concentrations by 35 to 81%, and induced a 4.5- to 16.9-fold increase in mean daily urinary excretion of the metal. In the acutely arsenic-poisoned case, the plasma arsenic concentration on day 7 was half the pretreatment value, while no clear decrease was observed in a chronically exposed subject. In 3 mercury cases, DMSA increased daily mercury urinary excretion 1.5-, 2.8- and 8.4-fold, respectively, while blood mercury concentrations remained below detection limits. No serious side effects were observed and 3 weeks after administration of the drug the clinical condition of all subjects was either stable or improved. These results indicate the efficacy of DMSA for lead poisoning in humans and provide a rationale for further investigating its usefulness in mercury and arsenic poisoning cases.

Adolescent↗