This document discusses the assessment of blood volume in patients with chronic heart failure (CHF), focusing on the measurement of total blood volume (TBV) to guide treatment and management. It highlights the heterogeneity in TBV among patients with volume overload, noting the presence of different red blood cell profiles such as true anemia and dilution-related pseudo-anemia. The findings suggest that quantifying TBV can significantly improve understanding and management strategies for volume overload in CHF.

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BLOOD VOLUME MEASUREMENT
...WHAT DO WE LEARN
AND CAN IT HELP IN THE ASSESSMENT OF
VOLUME OVERLOAD IN
CHRONIC HEART FAILURE ?
Wayne L. Miller, MD, PhD, FACC/HFSA
Division of Cardiovascular Diseases
Mayo Clinic, Rochester, MN
March 14, 2015
No Disclosures/Conflicts of Interest

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BLOOD VOLUME MEASUREMENT
3 Points:
1) Describe the method of quantitative blood volume
analysis in assessing volume overload in heart
failure patients.
2) Discuss data showing the extent of total blood
volume expansion in terms of plasma volume
and RBC profiles.
3) Highlight that not all volume overload is the same
and, therefore, impacts approach to management
and treatment in the individual patient.

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Volume Overload in
Chronic Heart Failure - Background
• Volume overload and fluid redistribution are front-
line features of the syndrome of decompensated
chronic heart failure (DHF).
• The clinical assessment of volume status,
particularly in identifying euvolemia with diuretic
therapy, remains a significant challenge.
• Standard surrogate markers such as the presence
or absence of elevated JVP, edema, +S3, or
dyspnea lack sensitivity and reliability.

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Volume Overload in Heart Failure
• Clinical question: Would being able to
quantitate total blood volume better define
volume status and help guide volume
assessment (and management), and also
inform HF pathophysiology?

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Measurement of Total Blood Volume
• Total Blood Volume = Red Cell Mass + Plasma
Volume can be quantitated using a standardized
semi-automated computer-based clinically
available laboratory test.
• Mayo Clinical Nuclear Medicine Lab uses BVA-100
Blood Volume Analyzer (Daxor Corp., NY)
[FDA approved 1998].
Technique: Indicator dilution principle
(concept introduced 1915)
Intravenous administration of low dose (5-30 µCi)
iodinated-131 labeled albumin (10mg).
W Miller, 2015

6. ©2013 MFMER | 3257511-6
Blood Sample Collection Time Points,
Minutes
Plasma
Volume,
mL
12 18 24 30 36
Standard deviation
Patient result 1.269% or 62.1 mL
Acceptance range <3.9%
Albumin transudation
analysis/slope (%/min)
Patient result 0.23
Reference range
Normal 0-0.4
High 0.4-0.5
Unusually high >0.5
Final mixed plasma volume=4,888 mL
Slope 0.00229
60

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Measurement of Total Blood Volume
• Red Blood Cell Mass (mL):
Calculated Mean Body Hematocrit (MBHct)
(adjusted from peripheral venous
hematocrit and corrected for trapped
plasma) is used to derive the measure
of RBC Mass.
(PV/1-MBHct) X MBHct = RBC Mass

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Measurement of Total Blood Volume
• Reference normal total blood volumes are
derived from an algorithm based on
deviations from ideal body weight
established from >100,000 measurements in
normal individuals of spectrum of age,
height, and body weight in both genders.
• Normal total blood volume is defined as
measured volumes which are within ±8% of
the expected normal volume.

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Measurement of Total Blood Volume
• Technique has been validated against
double-labelled chromium tagged RBCs
and I-125 albumin (“gold standard”) –
comparisons within ±1%
(Dworkin et al Am J Med Sci 334 (1): 37-40, 2007; Fairbanks et al
Blood Cells Mol Dis 22: 169-186, 1996).
Intra-individual reproducibility of volume
measurements: ±2.5%.

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Blood Volume Measurement
Values are reported as:
1) Absolute measured volumes in mLs,
(TBV, RBC Mass, and PV)
2) Expected normal reference volumes
(TBV, RBC Mass, and PV)
3) Percent deviation from normal expected
volumes [% excess (+) or deficit (-) from
normal]

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Clinical Study Data
• Total Blood Volume (TBV) was
measured at the time of hospital
admission in 50 patients with chronic
heart failure considered clinically to be
volume overloaded and admitted from
ED or by primary cardiologist for
treatment of decompensated HF.

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Clinical Characteristic of Patients Hospitalized for DCHF (N=50)
Variable Variable
Age, years 67±14 Etiology of HF Ischemic: 21
Non-Ischemic: 29
Gender, male 36 NT-proBNP,
pg/mL
4133
(2370, 9342)
BMI, kg/m² 37±10 Albumin, g/dL 3.6±0.4
LVEF, % 39±19 K+, mEq/L 4.4±0.5
Blood Pressure,
systolic, mmHg
121±17 Na+, mEq/L 139±4.0
Afib, no. 24 sCr, mg/dL
eGFR, mL/min
1.7±0.9
49±23
Diabetes, no. 22 BUN, mg/dL 42±22
Hypertension, no. 30 Hemoglobin,
g/dL
12.2±2.2
History of MI, no. 12 Hematocrit, % 38±6
OSA, no. 29 Plasma
Glucose, mg/dL
124±49

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Measured Total Blood Volume
(N=50)
Variable
Total Blood
Volume
Red Cell
Mass
Plasma
Volume
Measured Volume,
liters
Admission
7.4±1.9*
(4.6-14.5)
71mL/kg
(CL 61-83)
2.6±0.9*
(1.4-5.1)
4.8±1.3*
(2.7-9.4)
47mL/kg
(CL 38-52)
Expected Normal
Volume, liters
5.6±1.0
(3.8-8.8)
2.2±0.5
(1.4-3.6)
3.4±0.6
(2.4-5.3)
% Deviation from
Normal Volume,
Excess (+)/Deficit (-)
+32±23%
(0 to +107%)
+18±32%
(-39 to +92%)
+42±29%
(0 to +128%)
Data Expressed as Mean ± SD and (minimum-maximum range of values)
*p≤ 0.007W Miller, 2015

14. ©2014 MFMER | 3406030B-14
Patient (no.)
Patient (no.)
Patient (no.)
Total Blood Volume (% Deficit/Excess from Normal Volume)
Red Cell Mass (% Deficit/Excess from Normal Volume)
Plasma Volume (% Deficit/Excess from Normal Volume)
Frequency Distribution of Quantitated Volume
Deficit/Excess at Hospital Admission (N=50)
8
Line of Euvolemia
W Miller, 2015

15. ©2014 MFMER | 3406030B-15
Patient (no.)
Patient (no.)
Patient (no.)
Total Blood Volume (% Excess/Deficit from Normal Volume)
Red Cell Volume (% Excess/Deficit from Normal Volume)
Plasma Volume (% Excess/Deficit from Normal Volume)
Frequency Distribution of Quantitated Volume
Deficit/Excess at Hospital Admission (N=50)
8
Line of Euvolemia
W Miller, 2015
Marked Heterogeneity
in Patient to Patient
Intravascular Volumes

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Multiple RBC Profiles Identified
1) True anemia [low RBC mass and low
peripheral venous hemoglobin (Hb) values]
2) Dilution-related pseudo-anemia
secondary to PV expansion (normal RBC
mass but low Hb)
3) RBC polycythemia (excess RBC mass
with low/normal range Hb – pathologic PV
expansion). W Miller, 2015

17. ©2014 MFMER | 3406030B-17
Red Blood Cell Mass
Male
Female
Venous
Hemoglobin
(g/dL)
Excess (%)Deficit (%)
Shaded area = range of normal RBCM
(±10% of Expected Normal Volume)
♂
♀
W Miller, 2015
Mismatch of Peripheral Venous
Hemoglobin with RBC Mass
(N=50)

18. ©2014 MFMER | 3406030B-18
Red Blood Cell Mass
Male
Female
Venous
Hemoglobin
(g/dL)
Excess (%)Deficit (%)
Shaded area = range of normal RBCM
(±10% of Expected Normal Volume)
♂
♀
W Miller, 2015
By W.H.O. criteria 31/50 (62%) defined as anemic by
peripheral hemoglobin value.
By Quantitative BVA:
11/31 w/ True Anemia (RBCM deficit, low Hb; 22% of cohort)
8/31 w/ PV Dilution-related “Anemia”(Normal RBCM, low Hb)
12/31 w/ RBC Polycythemia+PV Excess (High RBCM, low Hb)

19. ©2014 MFMER | 3406030B-19
Red Blood Cell Mass
Male
Female
N=50
Venous
Hemoglobin
(g/dL)
Excess (%)Deficit (%)
Shaded area = range of normal RBCM
(±10% of Expected Normal Volume)
♂
♀
W Miller, 2015
Quantitated RBC Mass and Plasma Volume
are Needed Identify Relative Contributions of
Each To Overall Volume Overload

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SUMMARY
1) Marked heterogeneity in total blood volume
(range 0% to over 100% TBV expansion) in
patients with DCHF who had similar clinical
presentations with clinically determined volume
overload.
2) Multiple RBC profiles identified:
True anemia, dilution-related pseudo-anemia,
and RBC polycythemia (which is often concealed
by excess PV expansion)
3) This overall heterogeneity has implications for
the approach to volume management.

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SUMMARY
4) The quantitation of Total Blood Volume
(TBV) in the individual HF patient is
a useful tool in the assessment of
volume status (i.e., determining
hypervolemia or euvolemia, and red blood
cell contribution to volume overload).

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CONCLUSION
Chronic Heart Failure
Euvolemia Hypervolemia Hypovolemia
Not all Hypervolemia
Is the Same
↑↑↑ Expanded Total BV
Normal Red Cell Volume
↑↑↑ Plasma/Interstitial
Volume
Pathologic PV
Expansion
(w/ dilutional “anemia”)
↑↑↑↑↑ Expanded TBV
↑↑↑ Expanded RCV
(polycythemia)
↑↑ Expanded PV
Red Cell and
PV Expansion
↑↑↑ Expanded TBV
↓ RCV (true anemia)
↑↑↑↑PV
Homeostatic and
Pathologic PV Expansion
Marked Heterogeneity in Volume Overload
Impacts Treatment Plan: Diuretics, RBC Transfusion,
Phlebotomy
Congestion
Signs &
Symptoms
W Miller, 2015

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JACC-Heart Failure Vol 2, No.3
pp 298-305, 2014

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CP1024805-21
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