Cobalt (Blood)

Diagnostic Use

Blood cobalt testing is the preferred assessment for suspected toxicity in metal-on-metal hip implants. Urine testing is generally preferred for assessment of occupational exposure.

Cobalt-related systemic toxicity is a complex clinical syndrome with variable organ involvement including haematological (e.g. polycythaemia), endocrine (e.g. thyroid), neurological (e.g. hearing, balance and visual disturbances) and cardiovascular (e.g. myocardial) dysfunctions. Dose-response data and biokinetic modelling suggest blood Cobalt < 5100 nmol/L (<300 ug/L) is unlikely to be associated with clinically relevant symptoms for healthy individuals. However, different disease states e.g. renal failure, iron deficiency, sepsis, malnutrition, alcoholism or medication intake can predispose to Cobalt-induced toxicity at much lower levels. At this stage, no consensus can be reached as to a threshold blood level above which toxic systemic effects will predictably arise and therapeutic measures to be undertaken (Ref. 1).

Interpretation

Metal-on-Metal (MoM) hip replacements and blood Cobalt levels:

As there is a transient rise in blood Cobalt and Chromium level after hip replacement surgery, their testing should be offered at least 12 months after the surgery. Blood Cobalt level of <51 nmol/L (<3 ug/L) has been described by the American Academy of Orthopaedic Surgeons as one of the low risk factors; between 51-170 nmol/L (3-10 ug/L) as a moderate risk factor; >170 nmol/L (>10 ug/L) as a high risk factor for failure in total hip arthroplasty (Ref. 2). However, the role of a blood level is limited to being an adjunct to systemic clinical assessment and other investigative tools. Blood Cobalt level is just one factor in the evaluation. It should not be relied upon solely to determine the need for revision surgery (Ref. 2,3).

NZ Medsafe, in conjunction with the NZ Orthopaedic Association, issued a statement in June 2012 (accessed via https://www.medsafe.govt.nz/hot/alerts/mom-hip-implants.asp ), supporting the advice by UK MHRA, 2012 (Medicines and Healthcare Products Regulatory Agency) which described whole blood Cobalt level of >119 nmol/L (>7 ug/L) indicates potential for soft tissue reaction (especially if greater than previously; 2 tests performed 3 months apart).

Subsequent investigations revealed at the level of 119 nmol/L (7 ug/L) there is overall sensitivity of only 52%. Lowering the cut point to 85 nmol/L (5 ug/L) only slightly improves sensitivity but also loses specificity. While there is no revision statement from Medsafe since 2012, UK MHRA revised their alert in June 2017, advising:

“….there is no agreed threshold for whole blood metal levels that either predicts outcome, or mandates revision. Decisions to revise are influenced by patient factors, blood metal levels, imaging findings, and implant type and position. Other patient specific factors may need to be considered when interpreting results for blood metal levels.”

It also describes:

• Whole blood metal levels of Cobalt > 119 nmol/L ( > 7 ug/L) or Chromium > 134.5 nmol/L ( > 7 ug/L) in one or both metals, indicate the need for closer follow up and cross-sectional imaging
• For stemmed total hip replacements, whole blood metal Cobalt level <119 nmol/L (<7 ug/L) or whole blood Chromium level <134.5 nmol/L (<7 ug/L) may be associated with wear or corrosion at non-articulating surfaces
• MARS MRI or US scans should carry more weight in decision making than isolated whole blood metal levels alone
• Rising blood metal levels may indicate potential for soft tissue reaction
• After revision surgery, whole blood metal levels of Cobalt and/or Chromium are expected to fall and symptoms to improve. Persistent symptoms should be investigated for potential causes that include: failure of fixation, component loosening, infection and instability. If no cause is found, further blood metal level measurement and cross-sectional imaging should be considered.

More details can be accessed via: https://www.gov.uk/drug-device-alerts/all-metal-on-metal-mom-hip-replacements-updated-advice-for-follow-up-of-patients .

Serum versus whole blood Cobalt

While serum Cobalt levels were found to be more variable and considerably higher than whole blood in oral supplementation studies (Ref. 1), under the setting of metal-on-metal hip arthroplasty, serum and whole blood Cobalt were well correlated and similar (95% of the difference were within +/- 25 nmol/L, up to 170 nmol/L (Ref. 5), correlation slope at 0.99, up to 2500 nmol/L (Ref. 6)). In contrast, serum Chromium levels were about 1.6 fold higher then whole blood, with wider scatter.

Cautions:

Gadolinium and Iodine are known to interfere with metal tests. If either Gadolinium- or iodine-containing contrast media has been administered, a specimen should not be collected within 96 hours from the procedure.

As the concentration of Cobalt in plasma and urine are extremely low, specimen collection procedures require rigorous attention to clean specimen collection and handling procedures, to prevent contamination.

Reference Intervals

Non-exposed persons: 0 – 15 nmol/L

NZ WorkSafe has not set a specific biological exposure index for plasma cobalt.

Conversion of units

nmol/L = ug/L x 17

nmol/L = ppb x 17