Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements

Pamidi, Prasad V. A.; DeAbreu, Marlene; Kim, Donghak; Mansouri, Sohrab

doi:10.1016/j.cca.2008.11.007

Cited by 34 publications

(12 citation statements)

References 10 publications

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“…Under cell culture conditions, however, cyanocobalamin is readily converted to hydroxocobalamin due to light exposure, 12 with up to 80% converted after 10 d in culture 13 . While both forms of vitamin B 12 are red-colored, 7 LC/MS results showed that the form remaining in red colored mAb pools is hydroxocobalamin, consistent with a previous report for an IgG2 product 13 . Since the majority of the experimental pools were from glass bioreactors exposed to light for the 14 d culture duration, it can be assumed that the hydroxocobalamin form was present in both C-HCCF and RP-HCCF; therefore, hydroxocobalamin availability alone was not sufficient to cause red color for these mAbs.…”

Section: Discussionmentioning

confidence: 99%

“…Several culture medium components are colored in solution, including vitamins B 2 (riboflavin), 5 , 6 B 6 , and B 12 7 . Other medium components such as iron and copper can vary in color depending on oxidative state and the presence of other ions, and can interact with proteins to form highly stable complexes that remain intact throughout downstream processing 8 .…”

Section: Introductionmentioning

confidence: 99%

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Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest

Derfus

Dizon-Maspat

Broddrick

et al. 2014

mAbs

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While many antibody therapeutics are formulated at low concentration (~10–20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to the higher molecular density across a given path-length. Color is therefore a product quality attribute that must be well-understood and controlled, to demonstrate process consistency and enable clinical trial blinding. Upon concentration of an IgG4 product at the 2000 L manufacturing scale, variability in product color, ranging from yellow to red, was observed. A small-scale experimental model was developed to assess the effect of processing conditions (medium composition and harvest conditions) on final bulk drug substance (BDS) color. The model was used to demonstrate that, for two distinct IgG4 products, red coloration occurred only in the presence of disulfide reduction-mediated antibody dissociation. The red color-causing component was identified as vitamin B12, in the hydroxocobalamin form, and the extent of red color was correlated with the cobalt (vitamin B12) concentration in the final pools. The intensity of redness in the final BDS was modulated by changing the concentration of vitamin B12 in the cell culture media.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest

Derfus

Dizon-Maspat

Broddrick

et al. 2014

mAbs

View full text Add to dashboard Cite

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“…Although our experience suggests that hydroxocobalamin does not cause clinically significant interference with non-invasive pulse oximetry, there is evidence to suggest that co-oximetric blood gas analysis with several unique analyzers may be altered in the presence of hydroxocobalamin, specifically with false elevations of carboxyhemoglobin and methemoglobin concentrations and underestimation of true oxygen saturation values. 5 There is no available evidence regarding the accuracy of other commonly utilized oximetric monitoring modalities (e.g., cerebral oximetry) following hydroxocobalamin administration.…”

mentioning

confidence: 99%

Red urinary discolouration following hydroxocobalamin treatment for vasoplegic syndrome

Warner

Mauermann

Armour

et al. 2017

Can J Anesth/J Can Anesth

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“…More concerning is the increase in carboxyhemoglobin and methemoglobin and decrease in oxyhemoglobin from hydroxocobalamin interference observed with certain co-oximeters. 3 As smoke inhalation victims often demonstrate concomitant carbon monoxide and cyanide toxicities, initial blood gas measurements should be obtained prior to hydroxocobalamin administration. Our patient had a carboxyhemoglobin level of 20.5 % (normal, < 2.5 %) before hydroxocobalamin treatment, thereby confirming concurrent carbon monoxide poisoning.…”

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confidence: 99%

Wine-Colored Plasma and Urine from Hydroxocobalamin Treatment

Wong¹,

Pudek²,

Li³

2016

J GEN INTERN MED

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A 49-year-old male was admitted following a house fire that resulted in burns to 20 % of his total body surface area. Empiric hydroxocobalamin was given for presumed cyanide poisoning secondary to smoke inhalation. Plasma and urine from the patient were noted to have an intense dark red/purple hue (Fig. 1).Approximately 35 % of fire victims experience toxicity from cyanide, generated during pyrolysis of such synthetic materials as plastics, rugs, silks, and furniture. Cyanide inhibits cytochrome oxidase in the electron transport chain and blocks aerobic metabolism, causing a histotoxic hypoxia. Hydroxocobalamin chelates cyanide and forms the nontoxic, renally excreted cyanocobalamin. A common side effect of hydroxocobalamin is a stunning dark red/purple discoloration of the recipient's skin, mucosal membranes, and body fluids, including plasma and urine. Although the pigmentation is harmless and resolves spontaneously within days, it can cause analytical interference with a number of common chemistry, hematology, and coagulation tests.2 The clinical significance of these transient alterations remains to be determined. More concerning is the increase in carboxyhemoglobin and methemoglobin and decrease in oxyhemoglobin from hydroxocobalamin interference observed with certain co-oximeters.3 As smoke inhalation victims often demonstrate concomitant carbon monoxide and cyanide toxicities, initial blood gas measurements should be obtained prior to hydroxocobalamin administration. Our patient had a carboxyhemoglobin level of 20.5 % (normal, < 2.5 %) before hydroxocobalamin treatment, thereby confirming concurrent carbon monoxide poisoning.

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Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements

Cited by 34 publications

References 10 publications

Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest

Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest

Red urinary discolouration following hydroxocobalamin treatment for vasoplegic syndrome

Wine-Colored Plasma and Urine from Hydroxocobalamin Treatment

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