ASTM F1841-97(2005)

NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: F1841 − 97(Reapproved 2005)
Standard Practice for
Assessment of Hemolysis in Continuous Flow Blood
Pumps
This standard is issued under the fixed designation F1841; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
INTRODUCTION
The goal of blood pump development is to replace or supplement the function of the human heart.
As a result, continuous flow blood pumps, including roller pumps and centrifugal pumps, are
commonly used in clinical extracorporeal circulation. They are used not only for cardiopulmonary
bypass in routine cardiac surgery but also for ventricular assist, percutaneous cardiopulmonary
support, and extracorporeal membrane oxygenation.
Many investigators have attempted to develop an atraumatic blood pump. Hemolysis is one of the
most important parameters of blood trauma induced by blood pumps. However, comparative in vitro
evaluation of the reported results of hemolysis are difficult due to the lack of uniformity of the test
methods employed. Thus, it is necessary to standardize the method of performing in vitro hemolysis
tests for the evaluation of continuous flow blood pumps.
1. Scope 3. Terminology
1.1 This practice covers a protocol for the assessment of the 3.1 Definitions:
hemolytic properties of continuous flow blood pumps used in 3.1.1 continuous flow blood pump—a blood pump that
extracorporeal or implantable circulatory assist.An assessment produces continuous blood flow due to its rotary motion.
is made based on the pump’s effects on the erythrocytes over
3.1.2 free plasma hemoglobin—the amount of hemoglobin
acertainperiodoftime.Forthisassessment,arecirculationtest
(iron or heme-containing protein) in plasma.
is performed with a pump for 6 h.
3.1.3 hemolysis—damage to erythrocytes resulting in the
1.2 The values stated in both inch-pound and SI units are to
liberation of hemoglobin into the plasma.
be regarded as the standard. The SI units given in parentheses
3.1.4 Index of Hemolysis
are for information only.
3.1.4.1 normalized index of hemolysis—added grams of
1.3 This standard does not purport to address all of the
plasma free hemoglobin per 100 l of blood pumped, corrected
safety concerns, if any, associated with its use. It is the
for plasma volume using hematocrit and normalized by flow
responsibility of the user of this standard to establish appro-
rate and circulation time.
priate safety and health practices and determine the applica-
3.1.4.2 normalized milligram index of hemolysis— normal-
bility of regulatory limitations prior to use.
ized index of hemolysis expressed by milligram value of free
plasma hemoglobin.
2. Referenced Documents
3.1.4.3 modified index of hemolysis—mass of hemoglobin
2.1 ASTM Standards:
released into plasma normalized by the total amount of
F1830 PracticeforSelectionofBloodfor in vitroEvaluation
hemoglobin pumped through the loop.
of Blood Pumps
4. Formulas
This practice is under the jurisdiction of ASTM CommitteeF04onMedical and
Surgical Materials and Devices and is the direct responsibility of Subcommit-
4.1 Normalized Index of Hemolysis (N.I.H.) (1,2,3,4) :
teeF04.30 onCardiovascular Standards.
100 2 Ht 100
Current edition approved March 1, 2005. Published March 2005. Originally
N.I.H. g/100l 5∆freeHb 3V 3 3 (1)
approved in 1997. Last previous edition approved in 1997 as F1841 – 97. DOI:
100 Q 3T
10.1520/F1841-97R05.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Standards volume information, refer to the standard’s Document Summary page on The boldface numbers given in parentheses refer to a list of references at the
the ASTM website. end of the text.
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F1841 − 97 (2005)
5.2 Test Loop (4) (See Fig. 1)—The test loop consists of a
∆free Hb = increase of plasma free hemoglobin concentra-
total of 6.6 ft (2 m) of 3/8 in. (9.5 mm) ID polyvinylchloride
tion (g/L) over the sampling time interval,
tubing and a reservoir (typically, 13 by 13 cm) with a sampling
where:
port. The primed blood volume is 450 6 45 mL. A screw
V = circuit volume (L),
clamp,thatispositionedattheoutletside,isappliedtoproduce
Q = flow rate (L/min),
the required conditions for the left heart assist application (5
Ht = hematocrit (%), and
L/min against 100 mm Hg pressure head (that is, with the
T = sampling time interval (min).
pressure sampling ports at the same vertical height, the
4.2 Normalized Milligram Index of Hemolysis. (mg.N.I.H.) pressure in the outlet line of the pump is 100 mm Hg greater
(2,3,4): than in the inlet line)) and for the cardiopulmonary bypass
application (5 L/min against 500 mm Hg pressure head).
100 2 Ht 100
2mg.N.I.H.mg/100l 5∆freeHb 3V 3 3 (2)
(Optional testing at 350 or 700 mm Hg is also advisable.) To
100 Q 3T
monitor such pressure heads, the pressure monitoring lines are
4.3 Modified Index of Hemolysis (M.I.H.):
incorporated into the test loop both at the inlet and outlet tubes.
4.3.1 Modifiedindexofhemolysis(M.I.H.) (5,6)thatcanbe
An ultrasonic or electromagnetic flow probe is placed at the
written with no units or as (milligram of hemoglobin released
outlet side of the pump between the clamp and the reservoir to
into plasma/mg of total hemoglobin pumped through the loop):
monitor the flow rate. A thermistor is connected to the loop,
100 2 Ht 10
and the blood temperature is measured using a corresponding
M.I.H. 5∆freeHb 3V 3 3 (3)
100 Q 3T 3Hb
thermometer.
5.3 Pump Conditions—Pump flow rate is set at 5 6 0.25
where:
L/min at the circulating blood temperature of 37 6 1°C. The
Hb = total blood hemoglobin concentration at time
total pressure head is set at 100 6 3 mm Hg for the left heart
zero (mg/L), and
assist application and 500 6 15 mm Hg for cardiopulmonary
∆free Hb = increase of plasma free hemoglobin concentra-
bypass application. However, additional testing temperatures
tion (mg/L) over the sampling time interval.
canbechosenfrom0to42°Caccordingtotheintendedclinical
4.3.2 Among these indices, M.I.H. is recommended as an
use of the pump (for example, cardiopulmonary bypass may
index to express the degree of hemolysis caused by a blood
include cooling and warming during surgery.)
pumpinarecirculatingsystem.N.I.H.wasproposedtoaccount
5.4 Evaluation—The free plasma hemoglobin is determined
for the plasma volume based on the hemotocrit. Recent
by a clinically approved assay method (see 9.3). The free
development of less hemolytic blood pumps has since made it
plasma hemoglobin is standardized by calculating the M.I.H.
convenient to use mg. N.I.H. rather than N.I.H. However, both
the N.I.H. and the mg N.I.H. vary with hematocrit of the blood
6. Significance and Use
(6). M.I.H. is the recommended index to express the degree of
6.1 The objective of this practice is to standardize the
hemolysis caused by a blood pump in a recirculating system.
The M.I.H. equation corrects for differences in blood hemo- evaluation method for detecting the hemolytic effect of a
continuous flow blood pump used in extracorporeal circulation
globin concentration and hematocrit directly (5).
and circulatory assistance.
4.4 Testing Blood—Because the level of trauma-induced
hemolysis is different based on the source of blood, it is
7. Preparation of Hemolysis Test
necessary to identify the source of blood and its respective
7.1 Blood—The blood is obtained from human volunteers
index of hemolysis. Human, bovine, or porcine blood are
having normal body temperature, exhibiting no physical signs
recommended as the primary sources of testing blood (see
of disease and having hematological profiles in the normal
Practice F1830). It is preferable that the blood collected at a
acceptable range. (Donors are subjected to standard blood
standard slaughter house not be used due to the risk of being
donor screening procedures.) The donor should be fasted for 8
contaminated with fluids other than blood, unless the blood is
h or more to avoid additional hemolysis due to a high
obtained by controlled venipuncture.Although animal blood is
concentration of lipids in the blood. The delay in the collection
used in the development stage of a pump, it is suggested that
of the blood and the hemolysis test should not exceed 48 h of
pre-clinical evaluation tests be repeated with human blood.
refrigerated storage with the blood temperature kept between 2
5. Summary of Practice
and 8° C or more than2hat ambient condition. As an
5.1 Blood—The blood is obtained from human volunteers, alternative source of blood, animal blood can be used, but it is
cattle or pigs having normal body temperatures, no physical necessary that the source of blood is identified. The preferred
signs of disease, including diarrhea or rhinorrhea, and an animalbloodisbovineandporcine(SeePracticeF1830).Since
acceptable range of hemotological profiles. The blood should the use of completely fasted animals is impractical, it is
be collected by vascular puncture using a needle (14G or recommended that the animals be subjected to a 12-h fasting.
larger) and collected into the standard 500–2000 mL bags As a quality control measure, any blood having free plasma
containing citrate phospate dextrose adenine (CPDA-1) anti- hemoglobin of more than 20 mg/dLshould not be used for this
coagulant solution (See Appendix X2) or heparin sulfate (See test. In order to standardize the blood trauma testing, the blood
Appendix X3). The blood from a slaughterhouse can typically subjected to the test should have the hematocrit value
...