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Lab Director Information

  • ONLY if IVD manufacturer data is unavailable (see IVD Manufacturer Data), should the Hospital Laboratory Director make the decision to consider using the information from interference studies summarized from previous Hemopure clinical trials as a guideline for determining whether or not to report an assay result from a patient sample containing Hemopure.
  • The Assay Limitation tables that are provided are summary results; individual instrument and site results varied.
    • Data were compiled from 1994 to 2006 using triplicate samples of a known analyte concentration containing from zero to either 5.0 g/dL or 6.5 g/dL Hemopure.
    • A high and low clinically relevant analyte concentration was used in most interference tests conducted.
    • CLIA '88 and CAP criterions for acceptable error are provided in the Table: Acceptability recovery criterions below. However the criteria for acceptable error at individual clinical trial sites was determined by the laboratory directors or principal investigators at each site. Thus, acceptable concentrations of HBOC for reporting a result will vary depending on the criteria for acceptable error at each site - even when the same method is used.
    • No control was exerted to standardize the method used on these instruments: instrument Standard Operating Procedures as well as the type of reagent may have differed between testing sites.
    • For each instrument, the maximum plasma Hemopure concentration that would allow reporting of results for a particular test on a particular instrument is provided as either mean±Std Dev or median with minimum and maximum ranges from the different clinical trial sites.
  • Click on the instrument of interest in the below Table to go to the Assay Limitation Summary for that instrument.

Listing of Assay Limitation Tables Available from Clinical Laboratory Testing

Assay Type

IVD Manufacturer

Instrument

Blood Gas

Radiometer

ABL 505, 700, 725, EML 100

Cardiac Markers

Abbott

AxSYM

Cardiac Markers

Bayer

Centaur

Cardiac Markers

Roche

Elecsys

Cardiac Markers

Various

cTnI

Abbott Architect, Abbott i-STAT, Bayer Centaur, Beckman Access, Dade Behring Dimension, Ortho-Clinical Diagnostics Vitros ECi

cTnT

Roche Elecsys 2010

Chemistry

Beckman

Coulter CX3, CX7, CX9, LX20, LXi

Chemistry

Dade Behring

Dimension AR, XL, RXL

Chemistry

Ortho-Clinical Diagnostics

VITROS 250, 500, 700, 750, 950

Chemistry

Roche

Modular & Hitachi 917, 912, 911, 747

Coagulation

Diagnostica

Stago

Coagulation

Fibrometer

Fibrometer

Coagulation

IL

ACL 100, 200, 3000, 7000, Future +

Coagulation

MDA

180

Coagulation

Sysmex

1000, 1500, 6000, 7000

Therapeutic Drugs

Abbott

AxSYM

Therapeutic Drugs

Abbott

TDX

 

Table: Acceptability recovery criterions.

Since the clinical in-house Hemopure testing began in 1995, the acceptable recovery ranges for a particular analyte varied slightly from site to site as they were at the discretion of the site's Laboratory Director. The values below represent acceptable recovery as stated by CLIA '88 and CAP guidelines.

Analyte

Acceptable Error (±)

ALT

20%

ALBUMIN

10%

ALK PHOS

30%

AMYLASE

30%

AST

20%

BUN (UREA)

2 mg/dL or 9% (whichever is greater)

BILI, TOTAL

0.4 mg/dL or 20% (whichever is greater)

BILI, CONJUGATED (DIRECT)

0.4 mg/dL or 20% (whichever is greater)

CALCIUM

1.0 mg/dL

CHLORIDE

5%

CHOLESTEROL

10%

CK-MB

20%

CK, TOTAL

30%

CREATININE

0.3 mg/dL or 15% (whichever is greater)

GGT

15%

GLUCOSE

6.0 mg/dL or 10% (whichever is greater)

LDH

20%

LACTATE

15%

LIPASE

30%

MAGNESIUM

25%

PHOSPHOROUS

0.75 mg/dL

POTASSIUM

0.5 mmol/L

SODIUM

4.0 mmol/L

TOTAL PROTEIN

10%

TROPONIN I (low target ~0.1 ug/L)

0.05 ng/mL

TROPONIN I (high target ~1.5 g/L)

0.5 ng/mL

URIC ACID

17%

 

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Informational Results from Laboratory Testing for Hemopure Interferences.

Assay: Blood Gas

Instruments: Radiometer (ABL 505, 700, 725, EML 100)

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Calcium (Ionized)

4.7

6.5

2.3

1.5

6.6

7

Chloride

3.0

2.5

1.8

1.2

6.6

6

Glucose

2.5

2.5

0.0

2.5

2.5

2

Lactate

0.9

1.0

0.8

0.0

1.5

4

pCO2

4.5

4.5

2.8

2.5

6.6

2

pH

2.0

2.0

0.7

1.5

2.5

2

pO2

1.3

1.3

1.8

0.0

2.5

2

Potassium

3.6

2.5

1.7

2.5

6.6

5

Sodium

3.9

2.5

2.1

2.5

6.6

6

The data was collected from 1996 to 2005.

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Assay: Cardiac Markers

Instrument: Abbott AxSYM

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

CK MB

6.0

6.5

1.5

0.0

6.5

41

Troponin I

5.4

6.5

1.9

1.3

6.5

20

The data was collected from 1996 to 2005.

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Assay: Cardiac Markers

Instrument: Bayer Centaur

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

CK-MB

1.5

0.6

2.4

0.0

5.0

4

Troponin I

2.7

1.2

3.3

0.5

6.5

3

The data was collected from 2000 to 2006.

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Assay: Cardiac Markers

Instrument: Roche Elecsys

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

CK-MB

4.6

4.7

1.8

1.1

6.5

20

Troponin T

4.3

4.7

2.2

0.4

6.5

22

The data was collected from 1998 to 2007.

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Assays: Cardiac Markers
Instruments: Various

Title: Interference and Precision Studies of OPK Biotech's Hemopure (HBOC-201) on Commercial Cardiac Troponin Assays

Investigators: M.M. Murakami, H.E. Quist, F.S. Apple

Laboratory: Hennepin County Medical Center, Minneapolis, MN

Abstract: OPK Biotech Corporation has introduced the drug Hemopure (HBOC-201), an intravenous administered hemoglobin-based oxygen therapeutic to deliver oxygen to the body's tissues. It has been approved in South Africa for treating adult surgical patients who are acutely anemic, eliminating, reducing or delaying the need for allogenic red blood cell transfusions. To assist in the process to address FDA queries regarding safety and efficacy as a potential indications in cardiovascular ischemia and out-of-hospital trauma, the purpose of this study was to evaluate whether HBOC-201 interferes with the measurement of cardiac troponin; the standard biomarker for detection of myocardial injury. An interference study was conducted using NCCLS EP-7A guidelines. Three human plasma (heparin) pools based on cTnT concentrations (negative 0.0 ng/mL; medium 0.03 ng/mL; high 0.10 ng/mL) were spiked with varying concentrations of HBOC, ranging from 0.189 g/dL to 12.6 g/dL. The assays studied were: cTnI - Abbott Architect, Abbott i-STAT, Bayer Centaur, Beckman Access, Dade Behring Dimension, Ortho-Clinical Diagnostics Vitros ECi; cTnT - Roche Elecsys 2010. Each aliquot was measured twice with a negative control between each treated specimen. In phase I analytical interference, percent (%) recovery, and % cross-reactivity were evaluated. We observed acceptable recoveries, minimal interference and minimal cross-reactivity from HBOC, for concentration up to 12.6 g/dL, for the Abbott Architect cTnI, Dade cTnI, Beckman cTnI, and Roche cTnT assays. The Ortho, Bayer and i-STAT cTnI assays demonstrated poor recoveries and analytical interferences at HBOC concentrations as low as 0.63 g/dL.  Percent cross reactivity was calculated for all pools and was negligible for all assays (<0.00001%).

Phase I

Abbott Arch

Abbott i-STAT

Dade

Bayer

Beckman

Ortho

Roche

% Recovery

85-108

89-165

91-125

94-182

98-114

111-327

83-104


In phase II, a 10-day modified NCCLS precision study was carried out on the assays not prone to HBOC interference, as identified in phase I. The Abbott Architect, Beckman Access, Dade Dimension, and Roche Elecsys cTn assays demonstrated excellent within-run and total precision, range 1.2 to 6.2 %CV, at two HBOC concentrations of 6.3g/dL and 0.63g/dL. These observations were based on using a cTnT-positive plasma pool with a cTnT concentration (0.36 ng/mL) that would be indicative of myocardial injury.  In conclusion, 4 cardiac troponin assays were validated to be effective systems to accurately reflect in-vivo myocardial injury, without suspect of interference, cross-reactivity with or variability due to OPK Biotech's Hemopure HBOC-201 product.

(Provided, with consent, from Dr. Fred Apple, personal communication)

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Assay: Chemistry

Instruments: Beckman Coulter (CX3, CX7, CX9, LX20, LXi)

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Albumin

0.3

0.0

0.7

0.0

2.0

9

Alkaline Phosphatase

0.9

1.0

0.6

0.0

2.0

9

ALT

0.7

0.5

0.7

0. 0

2.5

9

Amylase

0.4

0.0

0.6

0.0

1.5

9

AST

0.4

0.5

0.5

0.0

1.6

9

Bilirubin (Direct)

0.0

0.0

0.1

0.0

0.1

7

Bilirubin (Total)

0.1

0.0

0.2

0.0

0.4

8

BUN

5.0

6.5

1.9

0.0

6.5

9

Calcium

4.6

6.5

2.5

0.0

6.5

11

Chloride

4.5

6.5

2.6

0.0

6.5

11

Cholesterol

2.9

2.5

0.7

2.0

4.3

9

Creatine Kinase

0.2

0.0

0.4

0.0

1.2

9

Creatinine (filtered)

5.2

5.8

1.6

2.5

6.5

6

Creatinine (not filtered)

1.7

1.5

0.8

1.0

2.6

3

CRP

1.3

1.3

1.8

0.0

2.6

2

GGT

0.4

0.3

0.5

0.0

1.5

9

Glucose

3.9

4.5

2.2

1.5

6.5

9

Lactate

0.8

0.8

1.1

0.0

1.5

2

LDH

2.1

1.0

2.7

0.0

6.5

8

Lipase

2.6

1.5

2.6

1.0

6.5

4

Magnesium

1.2

0.5

2.0

0.0

6.5

10

Phosphorus

0.8

0.5

1.3

0.0

4.5

10

Potassium

4.4

5.0

2.5

0.0

6.5

11

Sodium

4.4

5.0

2.5

0.1

6.5

11

Total Protein

0.3

0.4

0.2

0.0

0.5

9

Triglycerides

0.1

0.1

0.1

0.0

0.3

3

Uric Acid

0.3

0.4

0.4

0.0

1.0

9

The data was collected from 2005 to 2006.

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Assay: Chemistry

Instrument: Dade Behring Dimension (AR, XL, RXL)

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Albumin

0.8

0.0

1.3

0.0

4.0

10

Alkaline Phosphatase

0.3

0.5

0.4

0.0

1.0

9

ALT

0.7

0.6

0.2

0.5

1.0

10

Amylase

1.5

1.5

0.4

0.5

2.0

9

AST

0.9

1.0

0.2

0.5

1.0

10

Bilirubin (Direct)

0.0

0.0

0.0

0.0

0.0

7

Bilirubin (Indirect)

0.0

0.0

0.0

0.0

0.0

2

Bilirubin (Total)

0.1

0.0

0.2

0.0

0.5

9

BUN

5.4

5.0

0.8

4.5

6.5

9

Calcium

4.2

4.5

1.6

0.0

5.0

9

Chloride

5.9

6.5

0.8

5.0

6.5

8

Cholesterol

2.3

2.0

0. 9

1.2

4.0

8

Creatine Kinase

0.0

0.0

0.1

0.0

0.2

9

Creatinine (filtered)

5.5

6.5

1.5

2.6

6.5

8

Creatinine (not filtered)

1.9

1.5

2.1

0.0

6.5

7

GGT

0.4

0.5

0.2

0.0

0.6

9

Glucose

1.0

0.5

1.3

0.0

3.9

8

LDH

4.4

4.5

0.5

4.0

5.0

9

Lipase

3.5

2.5

2.7

1.5

6.5

3

Magnesium

0.5

0.5

0.5

0.0

1.6

9

Phosphorus

0.0

0.0

0.0

0.0

0.0

9

Potassium

6.0

6.5

0.8

5.0

6.5

9

Sodium

6.0

6.5

0.8

5.0

6.5

9

Total Protein

1.6

1.5

0.5

1.00

2.50

8

Uric Acid

1.0

0.6

1.2

0.00

3.00

10

The data was collected from 1994 to 2000.

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Assay: Chemistry

Instrument: Ortho-Clinical Diagnostics VITROS (250, 500, 700, 750, 950)

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Albumin

0.0

0.0

0.2

0.0

1.0

37

Alkaline Phosphatase

0.0

0.0

0.0

0.0

0.2

36

ALT

0.4

0.5

0.3

0.0

1.0

42

Amylase

0.5

0.5

0.5

0.0

2.0

45

AST

3.5

4.0

1.7

0.0

6.5

43

Bilirubin (Direct)

0.1

0.0

0.4

0.0

1.5

21

Bilirubin (Indirect)

0.6

0.0

1.9

0.0

6.5

20

Bilirubin (Total)

0.1

0.0

0.2

0.0

1.0

39

BUN

4.4

5.0

2.2

0.0

6.5

45

Calcium

4.0

5.0

1.9

0.0

6.5

40

Chloride

5.6

5.8

1.0

2.5

6.6

41

Cholesterol

3.2

3.0

1.5

1.0

6.5

22

Creatine Kinase

3.2

5.0

2.5

0.0

6.5

39

Creatinine (filtered)

6.2

6.5

0.7

4.3

6.5

22

Creatinine (not filtered)

1.5

1.8

0.6

0.0

4.0

33

GGT

0.7

0.6

1.1

0.0

6.5

37

Glucose

4.7

5.0

1.8

0.5

6.5

43

LDH

0.2

0.0

0.4

0.0

1.6

39

Lipase

4.9

5.0

1.3

1.5

6.5

45

Magnesium

2.5

2.3

2.2

0.0

6.5

42

Phosphorus

1.9

2.0

1.0

0.0

4.0

41

Potassium

5.7

6.5

1.0

2.5

6.5

39

Sodium

5.5

5.0

1.0

2.5

6.6

40

Total Protein

0.1

0.0

0.2

0.0

0.5

41

Uric Acid

3.9

5.0

1.7

0.0

6.5

39

The data was collected from 1996 to 2005.

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Assay: Chemistry

Instrument: Roche Modular & Hitachi (917, 912, 911, 747)

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Albumin

0.2

0.3

0.2

0.0

0.5

17

Alkaline Phosphatase

1.1

1.0

1.0

0.0

2.5

17

ALT

3.6

3.9

1.5

1.2

6.5

18

Amylase

1.8

1.2

1.4

0.5

5.0

17

AST

3.3

2.5

2.1

0.4

6.5

18

Bilirubin (Direct)

0.0

0.0

0.0

0.0

0.0

14

Bilirubin (Total)

0.5

0.0

1.0

0.0

2.5

18

BUN

4.3

4.3

1.6

2.5

6.5

17

Calcium

3.2

2.5

2.1

1.0

6.5

16

Chloride

4.4

4.30

2.0

1.0

6.5

15

Cholesterol

1.2

1.5

0.5

0.0

2.0

13

CO2

0.6

0.0

0.8

0.0

1.5

5

Creatine Kinase

3.4

2.5

2.2

0.0

6.5

18

Creatinine (filtered)

4.7

4.3

1.8

2.5

6.5

15

Creatinine (not filtered)

0.1

0.0

0.1

0.0

0.3

10

CRP

1.8

2.0

0.9

0.0

2.5

7

GGT

0.7

0.1

0.8

0.0

2.0

14

Glucose

4.5

4.3

2.0

0.5

6.5

17

HDL Cholesterol

1.9

2.0

0.9

0.5

2.6

5

Lactate

0.6

0.4

0.6

0.0

0.4

5

LDH

2.6

2.5

1.8

0.5

6.5

17

LDL Cholesterol

1.8

2.1

1.1

0.4

2.6

4

Magnesium

1.7

1.8

1.4

0.0

5.0

14

Phosphorus

2.2

1.0

2.5

0.0

6.5

17

Potassium

4.4

4.3

1.9

1.5

6.5

15

Sodium

4.6

4.3

1.8

2.5

6.5

15

Total Protein

1.3

1.2

0.8

0.3

3.0

17

Triglycerides

0.2

0.3

0.2

0.0

0.5

5

Uric Acid

0.31

0.3

0.3

0.0

1.0

14

The data was collected from 1999 to 2005.

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Assay: Coagulation

Instruments: Diagnostica Stago

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

aPTT

4.7

5.0

2.1

0.0

6.5

18

D-Dimer

0.9

0.9

1.3

0.0

1.8

2

Fibrinogen

4.4

5.1

2.3

0.0

6.5

21

PT(INR)

4.6

5.0

1.8

1.3

6.5

24

The data was collected from 1996 to 2005.

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Assay: Coagulation

Instruments: Fibrometer

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

aPTT

4.5

5.0

2.0

0.7

6.5

29

Fibrinogen

5.0

6.5

2.0

0.0

6.5

26

PT(INR)

5.6

6.5

1.6

0.0

6.5

29

The data was collected from 1994 to 2005.

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Assay: Coagulation

Instrument: IL ACL (100, 200, 3000, 7000, Future +)

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

aPTT

4.2

3.9

2.0

0.7

6.5

27

Fibrinogen

1.5

0.7

1.9

0.0

3.9

27

PT(INR)

4.3

4.5

2.2

0.0

6.5

26

The data was collected from 1997 to 2005.

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Assay: Coagulation

Instruments: Sysmex (1000, 1500, 6000, 7000)

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

aPTT

4.3

4.7

2.0

1.2

6.5

14

Fibrinogen

4.0

4.7

2.4

0.0

6.5

14

PT(INR)

4.7

4.7

1.4

2.5

6.5

14

The data was collected from 1996 to 2006

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Assay: Coagulation

Instrument: MDA 180

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number

aPTT

3.6

3.3

1.9

1.3

6.5

10

Fibrinogen

0.1

0.0

0.4

0.0

1.3

9

PT(INR)

3.6

3.9

0.8

2.6

5.0

9

The data was collected from 1995 to 2000.

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Assay: Therapeutic Drugs

Instrument: Abbott AxSYM

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Digoxin

5.2

5.0

1.8

0.0

6.5

13

Gentamicin

1.7

1.0

2.2

0.0

6.5

14

NAPA

3.6

5.0

2.4

0.0

6.5

7

Phenytoin

5.8

5.8

0.8

5.0

6.5

6

Procainamide

4.3

5. 0

1.8

1.0

6.5

8

Quinidine

2.9

2.8

2.1

0.0

5.0

8

Theophylline

5.2

5.0

1.2

3.0

6.5

9

Vancomycin

3.9

5.0

2.7

0.0

6.5

15

The data was collected from 1996 to 2005.

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Assay: Therapeutic Drugs

Instrument: Abbott TDX

 

Maximum allowable Hemopure concentration (g/dL) for acceptable results. Concentrations of Hemopure greater than these amounts will affect the assay such that result will be outside of acceptable recovery limits.

Analyte

Mean

Median

Std Dev

Min

Max

Number Instruments Tested

Amikacin

2.5

2.5

0.0

2.5

2.5

2

Digoxin

2.8

3.0

2.2