Effect of the Hemoglobin-Based Oxygen Carrier HBOC-201 on Laboratory Instrumentation: Cobas Integra, Chiron Blood Gas Analyzer 840, Sysmex™SE-9000 and BCT

Abstract

As part of a clinical trial, we evaluated the effects of the hemoglobin-based oxygen-carrier (HBOC) HBOC-201 (an ultrapurified, stroma-free bovine hemoglobin product, Biopure, Cambridge, MA, USA) on our routine clinical chemistry analyzer (Cobas Integra, F. Hoffmann-La Roche Ltd, Basel, Switzerland ), blood gas analyzer (Chiron 840, Chiron Diagnostics Corporation, East Walpole, MA, USA), routine hemocytometry analyzer (Sysmex SE-9000, TOA Medical Electronics Co Ltd., Kobe, Japan), hemostasis analyzer (BCT, Dade-Behring, Marburg, Germany) and bloodbanking system (Dia-Med-ID Micro Typing System, DiaMed AG, Cressier, Switzerland). The maximum tested concentration of HBOC-201 was 65 g/l. Of the 27 routine clinical chemistry tests challenged with HBOC-201, bilirubin-direct, creatine kinase MB-fraction (CK-MB), creatine kinase (CK), gamma-glutamyltransferase (GGT), magnesium and uric acid were influenced by even low concentrations of HBOC-201. These tests were excluded from use on the plasma of patients treated with HBOC-201. Since the non-availability of the cardiac marker CK-MB may lead to problems in acute situations, we introduced the qualitative Trop T-test (Boehringer Mannheim), which was not influenced. The applicability of another nine tests was limited by the concentration of the HBOC-201 in the patients' plasma. No interference of HBOC-201 in routine hemocytometry, hemostasis-analysis and red-blood cell agglutination detection (blood-bank tests) was observed. Although immediate patient-care was not compromised, routine use of hemoglobin-based oxygen carriers will have a strong impact on logistical management. The development of robust laboratory tests free from the interference of the pigmented oxygen carriers should therefore precede its introduction into routine transfusion medicine.

The Haemolytic, Icteric and Lipemic Sample Recommendations Regarding their Recognition and Prevention of Clinically Relevant Interferences. Recommendations of the Working Group on Preanalytical Variables of the German Society for Clinical Chemistry and the German Society for Laboratory Medicine

“…Recently, a set of therapeutic haemoglobin derivatives (so-called HBOC = haemoglobin-based oxygen carriers) that have been developed as blood substitutes, and appearing in concentrations of up to 50 of the patients are handled as described in specific literature references [14,15,16]. These materials import strong red colour to plasma and serum.…”

“…Therapeutic haemoglobin derivatives yield a visible haemoglobin concentration within the range of 10 -50 g/L, with an absorption spectrum indistinguishable from natural haemoglobin [14,15,16,22,23]. However, since haemoglobin concentrations of this magnitude rarely occur in vivo, the use of therapeutic haemoglobin derivatives is to be assumed at this plasma haemoglobin concentration.…”

“…The effect on several analytes measured in clinical chemistry has J Lab Med 2000; 24 (8) been studied with regard to their interference by haemolysis [11, 17, 26|. Likewise the changes caused by therapeutic haemoglobin derivatives are primarily due to optical interference [14,15,16].…”

Transfusion Alternatives in Trauma

“…However, a recent study found significant, albeit transient, increases in total peripheral resistance, systolic, diastolic, and mean arterial blood pressure, and decreases in heart rate, cardiac index and oxygen delivery in patients receiving the solution 16 . In addition, Wolthius and colleagues 17 reported that HBOC-201 confounds the laboratory detection of a number of serum components, including direct bilirubin, the MB fraction of creatine kinase, and magnesium. Kasper et al…”

When Blood Is Not an Option: Factors Affecting Survival After the Use of a Hemoglobin-Based Oxygen Carrier in 54 Patients with Life-Threatening Anemia

“…The same laboratory interference instructions were conveyed to each institution by electronic documents to the laboratory director and phone briefings or e-mails to the attending clinician in charge of the patient's care, indicating that HBOC-201 in the plasma caused interferences with colorimetric laboratory and clinical measurements. [35][36][37] The FDA gave individual patient approval, not as a CU protocol, so physiologic and laboratory data collection was not consistent across patients or the 49 CU sites, although specific common data items necessary to patient care and use of the product were recorded. Pretreatment data were collected 0.5 to 0.25 hours preceding, and closest to, the initial HBOC-201 infusion.…”