A Randomized Clinical Trial on Hemoglobin Dose and Patient Matching
Phase: NA
Conditions: Anemia
Sponsor: Haukeland University Hospital

 
 
1
 
 
 
A RANDOMIZED CLINICAL TRIAL ON HEMOGLOBIN DOSE 
AND PATIENT MATCHING 
 
 
 
NCT01328262 
 
 
 
 
 
 
 
 
 
 
 
November 1st, 2010 

 
 
2
CONTENTS 
 
1. SCIENTIFIC BACKGROUND…………………………………………………..............3 
2. OBJECTIVES AND STUDY DESIGN ..................................................................... 5 
3. PATIENTS ............................................................................................................... 5 
a. 
Inclusion Criteria ..........................................................................................................................5 
b. 
Exclusion Criteria .........................................................................................................................5 
c. 
Patient Enrolment ........................................................................................................................6 
d. 
Patient Consent Procedure .........................................................................................................6 
4. TRANSFUSION PROCEDURE ............................................................................... 6 
5. DATA COLLECTION .............................................................................................. 7 
a. 
Baseline Data Collection .............................................................................................................7 
i. 
Patient Baseline Demographic Data ...........................................................................................7 
b. 
Pre-Transfusion Data Collection .................................................................................................7 
i. 
Patient Data .................................................................................................................................7 
ii. 
Product Data ................................................................................................................................7 
c. 
Transfusion Data Collection ........................................................................................................7 
d. 
Post Transfusion Data Collection ................................................................................................8 
i. 
Patient Data .................................................................................................................................8 
ii. 
Product Data ................................................................................................................................8 
6. 
ADMINISTRATION ........................................................................................... 8 
b. 
Indemnity Arrangements .............................................................................................................8 
c. 
Patient Confidentiality ..................................................................................................................9 
d. 
Patient Withdrawal Policy ............................................................................................................9 
e. 
Ethical Standards ........................................................................................................................9 
f. 
Publication ...................................................................................................................................9 
7. REFERENCES ...................................................................................................... 10 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
3
1. SCIENTIFIC BACKGROUND 
 
Red blood cell concentrates (RBC) is the most frequently transfused blood component. The 
transfusion trigger for the product varies between different countries and different centres [1], 
as does the dosage (number of units) transfused under similar conditions [2]. Many centres 
experience a blood shortage periodically, and this may threaten patient safety and postpone 
planned operations [3].  The usual assumption used in the clinical practice is that a single 
unit of red blood cells transfused to an adult should result in an increment in circulating 
hemoglobin of 1 g/dl [4]. This practice is, however, based on an estimate on the basis of 
units, or at best volume. 
Furthermore, there is an existing difference depending on which type of RBCs is transfused; 
whole blood, filtrated RBCs, buffy coat removed RBCs or filtrated and buffy coat removed 
RBCs. This will decrease the hemoglobin levels in the unit by approximately 10 %, 10 % and 
20 % respectively.    
Many have discussed the advantage of standardizing the units of RBCs [5-7].  
Two different concepts are proposed; one is to standardise the unit, the other is to adjust the 
hemoglobin dose according to the patient’s blood volume, called hemoglobin dosing. 
Unfortunately, the total hemoglobin content of the units does not represent a homogeneity 
[5], and the blood volume of the patients vary as well [8]. Högman & Knutson performed a 
red cell apheresis study, demonstrating it was possible to collect either one or two units of 
RBCs without exceeding 13 percent of any donor's blood volume, provided the collected 
volume of blood in each unit was less than the current standard [5]. Applying a standard at 
45g of RBC Hb per unit was found to permit the collection of maximum RBC Hb and plasma 
in the evaluated population of Scandinavian donors (standardised units).  Hemoglobin dosing 
requires information on the hemoglobin content of each unit to be transfused, as well as the 
patients’ height, weight and actual and desired hemoglobin levels. 
 
In a study from Turkey, Arslan et al showed that matching the hemoglobin dose to the 
individual needs of the patient may reduce the total usage of red cell concentrates by 
approximately 30 % [9]. Calculating the patients’ total need of hemoglobin to achieve the 
targeted hemoglobin level made this possible. The hemoglobin dose was defined as 
hemoglobin concentration in the donor multiplied with donation volume. However the 
success rate was closely linked to patients’ weight; increased weight correlated with 
unwanted outcome.  In this study the total amount of transfused RBCs was reduced to 72 
from the original 104 units required. 

 
 
4
Holme et al have recently published data indicating that currently used formulas for 
estimation of a person's red cell volume (RCV) by weight and height are decades old and 
were based on the use of (51)Cr isotopes and on a sample population, which may not be 
reflective of today's population [10]. Their study demonstrated that (99m) Tc is a reproducible 
and precise method for determination of a person's RCV and that current formulas may 
significantly overestimate the RCV of today's population. This is likely the result of a shift in 
population characteristics over the past four decades as reflected by an increased mean 
body mass index (from 25 to 28 kg/m2), which has not resulted in a proportionally increased 
RCV. 
Although measuring of hemoglobin in the unit would represent the gold standard for the 
actually hemoglobin content in the unit, other methods can also be used. Preliminary data 
from Canada, Scotland and Norway have detected a close correlation between the 
hemoglobin content in the unit and the weight of the unit (Reikvam, Heddle, Prowse, Devine, 
Hervig, unpublished). This will allow us to simplify the methods used in the departments of 
immunology and transfusion medicine. By just measuring the weight of each unit, we can 
easily correlate and calculate the actually hemoglobin content in each unit.  
Studies have also indicated that the quality of the blood probably will be reduced with the 
storage time in the blood bank [11, 12]. In future studies we will also be able to correlate the 
hemoglobin increment to the age (days from donations) of the unit. This will bring information 
to the postulated theory of reduced function and survival of older RBCs versus newer RBCs 
[11, 12]. The blood volume have traditionally been calculated after standard formulas (e.g. 
Dubois and Dubois), but recent studies have suggested use of other formulas, which are 
probably more relevant for the population today [10].  
On the basis of this existing data, we have performed a pilot study to assess the feasibility of 
a multicentre study on hemoglobin dose and patient matching (Reikvam, Heddle, Roodie, 
Prowse, and Hervig, submitted). Patients administered for day-treatment with transfusion 
with RBCs at different centers in Norway, Scotland and Canada, were included in the study. 
Their hemoglobin concentration was measured before and after transfusion. 
We found that the hemoglobin content in RBC units showed considerable heterogeneousity. 
By correlating the hemoglobin increment with the patients’ weight or blood volume we found 
no significant correlation. However, when correlating the total hemoglobin dose given with 
the hemoglobin increment, we found a significant correlation. Furthermore, an even stronger 
correlation was found when the hemoglobin increment was correlated to hemoglobin dose 
divided with the patients’ estimated blood volume (Reikvam, Heddle, Roodie, Prowse, and 
Hervig, submitted).  Our study has made a contribution to the question about feasibility of 
hemoglobin dosage.  
 

 
 
5
As a result of variation in transfused blood volume and the blood donors’ hemoglobin 
concentration, besides the differences in the RBC preparation, the hemoglobin content in the 
final unit is far from standardized.  
New and better technologies in combination with new findings and experience have made it 
possible to achieve a higher degree of standardization. However, we still need further and 
larger studies on this area to make a conclusion about the feasibility and the clinical impact 
of the method. Therefore we want to go on with a randomized clinical trial on hemoglobin 
dose and patient matching to bring further information about the question about feasibility 
and possibility of hemoglobin dosage and standardization of the RBCs. 
 
 
2. OBJECTIVES AND STUDY DESIGN 
 
 
This is a randomized clinical study on hemoglobin dose and patient matching. The aim of the 
study is to evaluate whether the targeted hemoglobin increment (2 grams per decilitre) in the 
patient can be predicted from the hemoglobin dose/weight of the blood bag transfused. In the 
test group, the hemoglobin dose needed will be calculated, whereas in the control group, the 
prescribed number of red cell units will be transfused. 
 
3. PATIENTS 
Patients will be hospital in or out-patients, recruited by the investigator, who require 
transfusions of red cell concentrates and who fulfill the inclusion criteria. 
a. 
Inclusion Criteria 
• 
Patients receiving red cell transfusions or expected to receive one or 
more red cell transfusions 
• 
Patients over 16 years of age  
• 
Patients for whom height and weight information is available 
• 
Patients who have consented to participate 
 
b. 
Exclusion Criteria 
• 
Patients who are hemodynamically unstable (ongoing bleeding or 
hemolysis) 
• 
Patients with a known hemolytic anemia (congenital or acquired) 

 
 
6
• 
Patients with a positive Direct Antiglobulin Test (DAT) 
• 
Patients for whom informed consent has not been obtained 
• 
Patients where the hemoglobin concentration increment target is 
above 2g/dl. 
• 
Patients with auto- or alloantibodies against RBCs. 
 
c. 
Patient Enrolment 
Patients who meet the inclusion criteria will be invited to participate, and those 
who provide informed consent will be enrolled in the study. Patients will be 
randomized to standard transfusion or patient matched hemoglobin dosing 
transfusion based on the weight of the blood bag.  
 
d. 
Patient Consent Procedure 
The purpose and procedures of the study will be explained to prospective 
participants and their written consent obtained prior to their taking part in the 
study.  The patients will also be informed that they have the right to withdraw 
from the study at any time, without giving a reason, and this will not affect their 
future treatment in any way. 
 
4. TRANSFUSION PROCEDURE 
Patients will be transfused according to local practice for their clinical condition and 
may receive more than one red cell unit, up to a maximum of three units per 
transfusion.  Multiple units must be transfused consecutively with no disruption in the 
procedure. 
 
Data may be collected on more than one transfusion procedure for each patient, to 
allow assessment of factors affecting hemoglobin increment between and within 
patients. 
 

 
 
7
5. DATA COLLECTION 
a. Baseline Data Collection 
i. 
Patient Baseline Demographic Data 
The following information will be collected for all participating patients: 
• 
Age 
• 
Gender 
• 
Weight 
• 
Height 
• 
Primary diagnosis 
• 
ABO and Rh (D) blood type 
 
b. Pre-Transfusion Data Collection 
i. 
Patient Data 
Prior to transfusion the following data will be collected for the patient:- 
• 
Indication for transfusion 
• 
Hemoglobin level (within 24 hours prior to transfusion) 
 
ii. 
Product Data 
Prior to transfusion the following data will be collected for the red cell 
unit(s) to be transfused: 
• 
ABO and Rh type 
• 
Weight of the red cell unit(s) 
• 
Age of the red cell unit(s) 
 
c. Transfusion Data Collection 
The following data will be recorded for each transfusion: 
• 
Time transfusion started 
• 
Time transfusion completed. 
• 
Number of red cell units transfused (maximum 3 units) 
 

 
 
8
d. Post Transfusion Data Collection 
i. 
Patient Data 
Patients will have a blood sample taken (preferably from the arm 
contralateral to the transfusion site) between 15 minutes and 8 hours 
post completion of transfusion.  In the case of transfusion of multiple 
units, this sample will be taken after the final unit has been transfused.  
The following data will be recorded: 
• 
Hemoglobin level 
 
ii. 
Product Data 
• 
Weight of each red cell unit transfused (if not performed prior to 
transfusion) 
 
 
6. ADMINISTRATION 
a.      Sample size and Randomisation procedure 
 
The patients will be randomized to two groups, the test group receiving a 
calculated hemoglobin dose and a control group receiving the prescribed number of 
red cell units. Based on experience, the average hemoglobin increment in the control 
group will be 1.62 g/dl with a standard deviation of 0.7. To be sure to detect a 
difference between 1.62 g/dl and 2.0 g/dl hemoglobin increment, 55 transfusion 
episodes must be included in each group. To allow for 10% missing data, we will 
include 61 episodes in each group. 
The randomization itself is performed by a computer programme. 
 
b.       Indemnity Arrangements 
This is a study using data collected during routine treatment of the patient, 
with the possible exception of one additional blood sample to be taken for 
hemoglobin determination between 15 minutes and 8 hours post-transfusion.  
Therefore, no indemnity/insurance arrangements in addition to those already 
in place at the participating centres are required. 
 

 
 
9
c. 
Patient Confidentiality  
Participating site will be allocated a unique site identifying code and all 
patients will be given an associated trial number on entry to the study.  
Thereafter they will be referred to by that number and by their initials on all 
documentation to preserve their confidentiality. 
 
d. 
Patient Withdrawal Policy 
Patients may withdraw from the study at any time without giving a reason. 
 
e. 
Ethical Standards 
The protocol will be approved by the appropriate Research Ethics 
Committee/Institutional Review Board for each of the centres that enrol 
patients in the trial, and, where appropriate, by local Research and 
Development Management. This trial will be performed in accordance with the 
requirements of the ICH Tripartite Guideline for Good Clinical Practice, which 
is consistent with the principles laid down in the Declaration of Helsinki as 
adopted by the 18th WMA General Assembly Helsinki, Finland, June 1964 
and amended by the 29th WMA General Assembly, Tokyo, Japan, October 
1975, the 35th WMA General Assembly, Venice, Italy, October 1983, the 41st 
WMA General Assembly, Hong Kong, September 1989, the 48th WMA 
General Assembly, Somerset West, Republic of South Africa, October 1996 
and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. 
Note of Clarification on Paragraph 29 added by the WMA General Assembly, 
Washington 2002 
Note of Clarification on Paragraph 30 added by the WMA General Assembly, 
Tokyo 2004 
 
f. Publication  
The results will be published in an international peer-reviewed journal and will 
be presented at national and international scientific meetings. 
 

 
 
10
7. REFERENCES 
 
 
1. 
Use of blood products for elective surgery in 43 European hospitals. The 
Sanguis Study Group. Transfus Med 1994, 4(4):251-268. 
2. 
Hebert PC, Wells G, Martin C, Tweeddale M, Marshall J, Blajchman M, Pagliarello G, 
Sandham D, Schweitzer II, Boisvert D et al: Variation in red cell transfusion 
practice in the intensive care unit: a multicentre cohort study. Crit Care 1999, 
3(2):57-63. 
3. 
Sandborg E: Getting people to give blood. Vox Sang 2000, 78 Suppl 2:297-301. 
4. 
Wiesen AR, Hospenthal DR, Byrd JC, Glass KL, Howard RS, Diehl LF: Equilibration 
of hemoglobin concentration after transfusion in medical inpatients not actively 
bleeding. Ann Intern Med 1994, 121(4):278-230. 
5. 
Hogman CF, Knutson F: Standardized units of RBCs: is it time for 
implementation? Transfusion 2000, 40(3):330-334. 
6. 
Sweeney JD: Standardization of the red cell product. Transfus Apher Sci 2006, 
34(2):213-218. 
7. 
Hogman CF, Meryman HT: Red blood cells intended for transfusion: quality 
criteria revisited. Transfusion 2006, 46(1):137-142. 
8. 
Valeri CR, Dennis RC, Ragno G, Macgregor H, Menzoian JO, Khuri SF: Limitations 
of the hematocrit level to assess the need for red blood cell transfusion in 
hypovolemic anemic patients. Transfusion 2006, 46(3):365-371. 
9. 
Arslan O, Toprak S, Arat M, Kayalak Y: Hb content-based transfusion policy 
successfully reduces the number of RBC units transfused. Transfusion 2004, 
44(4):485-488. 
10. 
Holme S, Elfath MD, Heaton A, Whitley P, McNeil D: Prediction of red cell and 
blood volumes distribution by various nomograms: do current nomograms 
overestimate? Transfusion 2008, 48(5):910-916. 
11. 
Hamasaki N, Yamamoto M: Red blood cell function and blood storage. Vox Sang 
2000, 79(4):191-197. 
12. 
Koch CG, Li L, Sessler DI, Figueroa P, Hoeltge GA, Mihaljevic T, Blackstone EH: 
Duration of red-cell storage and complications after cardiac surgery. N Engl J 
Med 2008, 358(12):1229-1239.