Platinum toxicity

Background

• Most often due to platinum-based anti-neoplastic drugs (e.g. cisplatin, carboplatin)
• Can also occur with occupational exposure (skin or dust inhalation) to platinum-soluble salts, used as industrial catalysts and in some specialized photographic processes
• Cytotoxicity results when platinum-containing complexes form inter or intra-strand platinum-DNA cross-linkages

Clinical Features

• Platinum based chemotherapy toxicity,
  • Peripheral and cranial neuropathy (ototoxicity, optic neuropathy): common, often permanent
  • Nephrotoxicity: dose-limiting toxicity
    • Multifactorial, typically prevented with forced diuresis
    • Electrolyte abnormalities due to tubular damage; in particular renal salt wasting syndrome
  • Mucositis,nausea/vomiting
  • Hepatic steatosis
  • Mild=moderate myelosuppression
• Occupational exposure,
  • History of exposure to platinum=soluble salts, such as sodium chloroplatinate, ammonium chloroplatinate, platinum tetrachloride
  • Dust can sensitize airways, trigger Asthma/reactive airway symptoms
  • Dermatitis
  • Irritating to eyes, mucous membranes
  • Metallic platinum usually does not typically cause similar effects

Background

Heavy metal toxicity results from exposure to metals like lead, mercury, arsenic, or cadmium, which interfere with cellular function. Exposure may occur occupationally, environmentally, through ingestion, or from alternative medicines. Chronic toxicity can present insidiously, while acute toxicity may mimic sepsis or encephalopathy. Diagnosis is often delayed due to nonspecific symptoms.

Clinical Features

Symptoms depend on the metal and exposure duration but may include:

Neurologic: Peripheral neuropathy, confusion, tremor, encephalopathy

GI: Abdominal pain, nausea, vomiting, diarrhea, anorexia

Heme: Anemia (especially microcytic or hemolytic), basophilic stippling (lead)

Renal: Tubular dysfunction, proteinuria, Fanconi syndrome

Dermatologic: Mees’ lines (arsenic), hyperpigmentation, hair loss

Others: Fatigue, weight loss, hypertension (cadmium), immunosuppression

Differential Diagnosis

Sepsis or systemic inflammatory response

Drug toxicity or overdose

Metabolic disorders (e.g., porphyria, uremia)

Psychiatric illness (if symptoms are vague or bizarre)

Neurologic diseases (e.g., Guillain-Barré, MS, Parkinson’s)

Vitamin deficiencies (e.g., B12, thiamine)

Evaluation

Workup

History: Occupational exposures, home remedies, hobbies (e.g., jewelry making, battery recycling), diet, water source, imported goods

Labs:

• CBC, CMP, urinalysis
• Blood lead level, serum/urine arsenic, mercury, or cadmium (based on suspicion)
• Urine heavy metal screen (note: spot testing may require creatinine correction)

Imaging: Abdominal X-ray (radiopaque material in GI tract, especially with lead)

EKG: Evaluate for QT prolongation or arrhythmias in severe cases

Diagnosis

Confirmed by elevated blood or urine levels of the specific metal in the context of clinical findings. Hair and nail testing are unreliable for acute toxicity. Interpret results with toxicologist input if possible.

Management

Remove the source of exposure (e.g., occupational control, GI decontamination if recent ingestion)

Supportive care: IV fluids, seizure control, electrolyte repletion

Chelation therapy (in consultation with toxicology or Poison Control):

Lead: EDTA, dimercaprol (BAL), succimer

Mercury/arsenic: Dimercaprol or DMSA

Cadmium: No effective chelation—focus on supportive care

Notify local public health authorities if exposure source is environmental or occupational

Disposition

Admit if symptomatic, unstable, or requiring chelation

Discharge may be appropriate for asymptomatic patients with low-level exposure and outpatient follow-up

Arrange toxicology or environmental medicine follow-up for source control and serial testing

See Also

• Aluminum toxicity
• Antimony toxicity
• Arsenic toxicity
• Barium toxicity
• Bismuth toxicity
• Cadmium toxicity
• Chromium toxicity
• Cobalt toxicity
• Copper toxicity
• Gold toxicity
• Iron toxicity
• Lead toxicity
• Lithium toxicity
• Manganese toxicity
• Mercury toxicity
• Nickel toxicity
• Phosphorus toxicity
• Platinum toxicity
• Selenium toxicity
• Silver toxicity
• Thallium toxicity
• Tin toxicity
• Zinc toxicity

Evaluation

• CBC, BMP, Mg/Phos, LFTs, UA
• Serum platinum levels
  • Unexposed: <0.04mcg/ml
  • Peak levels during platinum-based chemotherapy: 0.6-1.8mcg/mL
  • Increased risk of toxicity if >1.8mcg/ml

Management

• Decontaminate if occupational exposure
• Predominantly supportive/symptomatic treatment
• Volume resuscitate if AKI, correct electrolyte abnormalities
• Respiratory support, bronchodilators if needed for inhalational exposure
• Sodium thiosulfate: for cisplatin overdose
  • Binds free platinum to form nontoxic thiosulfate-cisplatin complex, prevents renal tubule damage
  • Binds to free platinum to form a nontoxic thiosulfate-cisplatin complex, limits renal tubular damage
  • 4g/m2 IV bolus over 15m within 1-2h of overose, then 12g/m2 infusion over 6h
  • Continue maintenance dosing until urinary platinum levels < 1mcg/mL