Advertisement
Case Report|Articles in Press

Hydroxocobalamin Interference With Chromogenic Anti-Xa Assay in a Patient on Mechanical Circulatory Support

Published:February 28, 2023DOI:https://doi.org/10.1053/j.jvca.2023.02.035
      HYDROXOCOBALAMIN (vitamin B12A), a precursor to cyanocobalamin, is United States Food and Drug Administration-approved for treating cyanide toxicity. In published case series and small retrospective cohort studies, it has been used off-label for refractory shock due to catecholamine-resistant vasoplegia in various populations.
      • Boettcher BT
      • Woehlck HJ
      • Makker H
      • et al.
      Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases.
      • Sacco AJ
      • Cunningham CA
      • Kosiorek HE
      • et al.
      Hydroxocobalamin in refractory septic shock: A retrospective case series.
      • Cios TJ
      • Havens B
      • Soleimani B
      • et al.
      Hydroxocobalamin treatment of refractory vasoplegia in patients with mechanical circulatory support.
      • Shah PR
      • Reynolds PS
      • Pal N
      • et al.
      Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: A case series.
      • Furnish C
      • Mueller SW
      • Kiser TH
      • et al.
      Hydroxocobalamin versus methylene blue for vasoplegic syndrome in cardiothoracic surgery: A retrospective cohort.
      The proposed mechanism behind using hydroxocobalamin for vasoplegia is its ability to scavenge nitric oxide and hydrogen sulfide, thereby attenuating profound vasodilation in inflammation.
      • Gerth K
      • Ehring T
      • Braendle M
      • et al.
      Nitric oxide scavenging by hydroxocobalamin may account for its hemodynamic profile.
      ,
      • Cai Y
      • Mack A
      • Ladlie BL
      • et al.
      The use of intravenous hydroxocobalamin as a rescue in methylene blue-resistant vasoplegic syndrome in cardiac surgery.
      Hydroxocobalamin is deep red in color and is known to cause interference with numerous laboratory parameters, including those using cooximetry, clot-based coagulation methods, and, particularly, colorimetric tests.
      • Pamidi P
      • DeAbreu M
      • Kim D
      • et al.
      Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements.
      Cyanokit US Prescribing Information.
      • Dang S
      • Tsui AK
      • Herndon R
      • et al.
      Hydroxocobalamin interference in routine laboratory tests: Development of a protocol for identifying samples and reporting results from patients treated with Cyanokit.
      In terms of coagulation parameters, there are known effects of hydroxocobalamin on activated partial thromboplastin time (aPTT), prothrombin time (PT) and international normalized ratio (Table 1), but there are scarce reports of its effect on the anti-Xa assay, a chromogenic test frequently used for unfractionated heparin infusion monitoring.
      Cyanokit US Prescribing Information.
      ,
      • Beckerman N
      • Leikin SM
      • Aitchinson R
      • et al.
      Laboratory interferences with the newer cyanide antidote: Hydroxocobalamin.
      Here, the authors report a case of undetectable anti-Xa levels in a heparinized patient who received hydroxocobalamin for refractory shock while on mechanical circulatory support (MCS).
      Table 1Laboratory Interference Observed With In Vitro Samples of Hydroxocobalamin
      Reproduced with permission from BTG International Inc.
      Laboratory Parameter No Interference Observed Artificially Increased
      ≥10% interference observed on at least 1 analyzer.
      Artificially Decreased
      ≥10% interference observed on at least 1 analyzer.
      Unpredictable Duration of Interference
      Clinical chemistry
      • Calcium
      • Sodium
      • Potassium
      • Chloride
      • Urea
      • GGT
      • Creatinine
      • Bilirubin
      • Triglycerides
      • Cholesterol
      • Total protein
      • Glucose
      • Albumin
      • Alkaline phosphatase
      • ALT
      • Amylase
      • Phosphate
      • Uric Acid
      • AST
      • CK
      • CKMB
      • LDH
      24 h with the exception of bilirubin (up to 4 d)
      Hematology
      • Erythrocytes
      • Hematocrit
      • MCV
      • Leukocytes
      • Lymphocytes
      • Monocytes
      • Eosinophils
      • Neutrophils
      • Platelets
      • Hemoglobin
      • MCH
      • MCHC
      • Basophils
      12-16 h
      Coagulation
      • aPTT
      • PT (quick or INR)
      24-48 h
      Urinalysis
      • pH (with all doses)
      • Glucose
      • Protein
      • Erythrocytes
      • Leukocytes
      • Ketones
      • Bilirubin
      • Urobilinogen
      • Nitrite
      pH (with equivalent doses of <5 g) 48 h up to 8 d; color changes may persist up to 28 d
      NOTE. Analyzers used: ACL Futura (Instrumentation Laboratory), AxSYM/Architect (Abbott), BM Coasys110 (Boehringer Mannheim), CellDyn 3700 (Abbott), Clinitek 500 (Bayer), Cobas Integra 700, 400 (Roche), Gen-S Coultronics, Hitachi 917, STA Compact, Vitros 950 (Ortho Diagnostics).
      Abbreviations: ALT, alanine transaminase; AST, aspartate transaminase; aPTT, activated partial thromboplastin time; CK, creatine kinase; GGT, gamma-glutamyltransferase; INR, international normalized ratio; LDH, lactate dehydrogenase; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin content; MCV, mean corpuscular volume; PT, prothrombin.
      low asterisk Reproduced with permission from BTG International Inc.
      ≥10% interference observed on at least 1 analyzer.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Cardiothoracic and Vascular Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Boettcher BT
        • Woehlck HJ
        • Makker H
        • et al.
        Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases.
        Int J Surg Case Rep. 2022; 98107488
        • Sacco AJ
        • Cunningham CA
        • Kosiorek HE
        • et al.
        Hydroxocobalamin in refractory septic shock: A retrospective case series.
        Crit Care Explor. 2021; 3: e0408
        • Cios TJ
        • Havens B
        • Soleimani B
        • et al.
        Hydroxocobalamin treatment of refractory vasoplegia in patients with mechanical circulatory support.
        J Heart Lung Transplant. 2019; 38: 467-469
        • Shah PR
        • Reynolds PS
        • Pal N
        • et al.
        Hydroxocobalamin for the treatment of cardiac surgery-associated vasoplegia: A case series.
        Can J Anesth. 2018; : 560-568
        • Furnish C
        • Mueller SW
        • Kiser TH
        • et al.
        Hydroxocobalamin versus methylene blue for vasoplegic syndrome in cardiothoracic surgery: A retrospective cohort.
        J Cardiothorac Vasc Anesth. 2020; 34: 1763-1770
        • Gerth K
        • Ehring T
        • Braendle M
        • et al.
        Nitric oxide scavenging by hydroxocobalamin may account for its hemodynamic profile.
        Clin Tox. 2006; 44: 29-36
        • Cai Y
        • Mack A
        • Ladlie BL
        • et al.
        The use of intravenous hydroxocobalamin as a rescue in methylene blue-resistant vasoplegic syndrome in cardiac surgery.
        Ann Card Anaesth. 2017; 20: 462-464
        • Pamidi P
        • DeAbreu M
        • Kim D
        • et al.
        Hydroxocobalamin and cyanocobalamin interference on co-oximetry based hemoglobin measurements.
        Clinica Chimica Acta. 2009; 401: 63-67
      1. Cyanokit US Prescribing Information.
        BTG International Inc, West Conshohocken, PAMay 2021
        • Dang S
        • Tsui AK
        • Herndon R
        • et al.
        Hydroxocobalamin interference in routine laboratory tests: Development of a protocol for identifying samples and reporting results from patients treated with Cyanokit.
        Clin Biochem. 2021; 91: 31-38
        • Beckerman N
        • Leikin SM
        • Aitchinson R
        • et al.
        Laboratory interferences with the newer cyanide antidote: Hydroxocobalamin.
        Semin Diagn Pathol. 2009; 26: 49-52
        • Bates SM
        • Weitz JI.
        Coagulation assays.
        Circulation. 2005; 112: e53-e60
        • Olson JD
        • Arkin CF
        • Brandt JT
        • et al.
        College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: Laboratory monitoring of unfractionated heparin therapy.
        Arch Pathol Lab Med. 1998; 122: 782-798
      2. HemosIL Heparin Package Insert.
        Instrumentation Laboratory Company, Lexington, MAMarch 2005
        • Carlsson CJ
        • Hansen HE
        • Hilsted L
        • et al.
        An evaluation of the interference of hydroxocobalamin with chemistry and co-oximetry tests on nine commonly used instruments.
        Scand J Clin Lab Invest. 2011; 71: 378-386
        • Teien AN
        • Lie M
        • Abildgaard U.
        Assay of heparin in plasma using a chromogenic substrate for activated factor X.
        Thromb Res. 1976; 8: 413-416
        • Vera-Aguilera J
        • Yousef H
        • Beltran-Melgarejo D
        • et al.
        Clinical scenarios for discordant Anti-Xa.
        Adv Hematol. 2016; 4054806
        • McMichael A
        • Ryerson LM
        • Ratano D
        • et al.
        2021 ELSO adult and pediatric anticoagulation guidelines.
        ASAIO J. 2022; 68: 303-310