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Hematological changes induced by erythrocytapheresis

How to cite this article: Domínguez-Morales SK, Moreno-López LC, Gallardo JM, Paniagua JR. Hematological changes induced by erythrocytapheresis. Rev Med Inst Mex Seguro Soc. 2015 Jul-Aug;53(4):422-9.



Received: May 14th 2014

Accepted: March 25th 2015

Hematological changes induced by erythrocytapheresis

Sindy Karina Ibeth Domínguez-Morales,a Luis Carlos Moreno-López,a Juan Manuel Gallardo,b José Ramón Paniaguab

aLaboratorio de Patología Clínica, Centro Médico “The American British Cowdray”

bUnidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de Especialidades, Centro Médico Nacional “Siglo XXI”, Instituto Mexicano del Seguro Social

Distrito Federal, México

Communication with: Juan Manuel Gallardo

Telephones: (55) 5627 6900, extension 21371


Background: Although automated cell separators (apheresis) have undergone a lot of technical refinements, the effect of the procedure on hematological indices of donors is rarely taken into account. The purpose of this study is to identify potential hematologic changes in donors undergoing erythrocytapheresis.

Methods: 30 apparently healthy adult donors were evaluated. Erythrocytapheresis procedure was performed using automated equipment. Hematologic measurements (hemoglobin, hematocrit, white blood cells counts and platelets) were analyzed before and after erythrocytapheresis in all donors.

Results: We observed a significant decrease in the donors in hemoglobin (p <0.0001), hematocrit (p <0.0001), leukocytes (p <0.0001), lymphocytes (p = 0.0267), and platelets (p <0.0001). On the other hand, we found no changes in segmented, monocytes, eosinophils and basophils post erythrocytapheresis.

Conclusion: In this study we found a significant drop in complete blood count in blood donation procedure by erythrocytapheresis; there are hematological changes in both red and white cells in all donors; however, none of donors manifested symptoms of thrombocytopenia or anemia. This study demonstrates hematological changes post-donation and therefore requires larger multicenter studies, in order to establish guidelines for donors’ safety in apheresis and also help in assessing donor suitability, especially given the present trend of double product apheresis collections.

Keywords: Blood donors; Erythrocytes; Blood banks; Blood component removal

Apheresis is a procedure increasingly used for general or specific collection of blood components from a donor, such as plasma, erythrocytes, leukocytes, or platelets, which may be removed or retained, and the remnant retransfused back to the donor.1 Several types of apheresis include erythrocytapheresis, leukapheresis, plasmapheresis, and plateletpheresis. All these procedures are relatively safe for the donor.2,3

Erythrocytapheresis, beyond just serving to obtain normal blood derivatives, has also been shown to have fundamental therapeutic utility in treating conditions such as polycythemia,4 hereditary hemochromatosis,5 idiopathic hemochromatosis 6, and many other diseases (Table I).

Table I Examples of clinical utility that has been given to the Apheresis in its different variants
Author Procedure and utility
Pérez E, et al.20 Plasmapheresis in Guillain Barre syndrome.
Gutiérrez J, et al.21 Plasma exchange in acute pancreatitis induced by hypertriglyceridemia.
León A, et al.22 Plasmapheresis in rapidly progressing Glomerulonephritis.
Lora CG, Navarro JR.23 Plasmapheresis in Lambert-Eaton myasthenic syndrome.
Daza J, Roncallo A.24 Plasmapheresis in Neuromyelitis optica.
Conte A, et al.25 Plasmapheresis in APS with development of catastrophic syndrome.
Martínez A, et al.26 Plasmapheresis in persistent HELLP syndrome.
Euler H, et al.27 Plasmapheresis in systemic lupus erythematosus nephritis.
DAU P.28 Therapeutic plasma exchange in polymyositis and Dermatomyositis.
Mellwig K, et al.29 Plasma exchange therapy for LDL-C reduction in patients with severe hypercholesterolemia.
Mariani R, et al.30 Eritrocitaferesis in patients with hemochromatosis and severe organ damage.
Gutiérrez C, et al.31 Eritroferesis in neonatal Polycythemia.
M. Medina32 Therapeutic plasma exchange in different pathologies: syndrome of
Goodpasture, hyperviscosity syndrome, multiple sclerosis etc.
Black V, et al.33 Exanguineo partial transfusion of plasma in neonates with hyperviscosity syndrome.

In modern blood banks, the apheresis procedure is becoming more common for the advantages of both the recipient and the donor at once. The effect of apheresis in the donor, has been a subject unexplored as it is healthy subjects with controlled low volume and because the attention in the procedure has been focused more on the receiver or the patient who is subjected plasmapheresis as a therapeutic method.7

When searching Pubmed for the word "erythropheresis" we found 21 items in total, 17 of which relate to humans. On the other hand, it has been reported that iron deficiency could be an important consequence for the donor,8 therefore, other blood components may also be affected.

The purpose of this work was to study hematologic changes occurring in the donor after the erythropheresis.




Cross-sectional study of altruistic blood donors. The protocol was reviewed by the Education and Research Division of the Centro Médico ABC, where both technical and ethical procedures are reviewed and approved.



The donor population consisted of 30 subjects, men, aged between 18 and 65 apparently healthy who gave their informed consent to participate in this study. All donors were captured over a period of 31 calendar days and met the requirements established in the Mexican Official Law (NOM) NOM-253-SSA-002 of the Secretaria de Salud, which regulates the activities relating to the provision of blood and blood components for therapeutic purposes. In summary, donors in Mexico should be: legal adults and no more than 65  years, over 50 kg weight, free of infectious diseases, without consumption of antibiotics, not having undergone any dental procedure in the last week, and not suffering from chronic degenerative diseases, among other regulations.9

Besides what is indicated in NOM for donors in Mexico, all donors received a general medical evaluation consisting of a medical examination to rule out recent (within the month) use of multivitamins, dietary supplements, iron, drugs, tobacco, alcohol, history of gastrointestinal or genitourinary bleeding, personal or family history of anemia, abnormal coagulation or bleeding, hemoglobinopathies, recent infections of any kind, heart failure, hepatic, renal or venous, chronic degenerative diseases such as arthritis, hypertension, diabetes mellitus and cancer. The same rule states that for donating a double package of erythrocytes obtained by apheresis, the donor should have a weight greater than 70 kg and that post donation, the subject should have more than 11 g/dL hemoglobin.9


Erythropheresis procedure

All patients donated a total volume of 400 mL (into two 200 mL globular packets each). The erythropheresis was performed using a commercial device (ALYX Collection System components, Fenwal, Inc. Lake Zurich, IL, USA). Cell separation was established as a standard procedure in the blood bank of the Centro Médico ABC in healthy volunteer subjects. The procedure was carried out under aseptic and antiseptic conditions, and following the manufacturer's instructions. All blood samples were collected just before starting the erythropheresis (from a vein in the forearm) and after the procedure.

All erythropheresis procedures were performed following standard procedures used in the blood bank and the instructions of the equipment manufacturer using a system of closed apheresis, anticoagulation based on the use of citrate dextrose acid (ACD) in ratio of 1: 12.10. The end point of each procedure was established when they had obtained 200 mL of erythrocytes per unit (two units per donor) and a flow of 40 mL/min. Table II shows the length and volume of blood, anticoagulant and saline used during erythropheresis.

Table II Control of the erythropheresis process
Anticoagulant vol.
Saline vol (mL) Vol. blood processed (mL)
Average 24.77 120.1
466.00 953.53
SD 4.56 6.72 41.88 107.21
Max 41 134 522 1069
Min 20 106 377 460
N =

30 30 30 30
min: minutes, vol: volume, mL: millilitres, sd: standard deviation, Max: maximum value, Min: minimum value, N: number

Hematological and biochemical analysis

Both the measurement of hematocrit and hemoglobin determination by the cyanmethemoglobin method, 11 as well as platelets, leukocytes, segmented, lymphocytes, monocytes, eosinophils and basophils are analyzed using an automated device (Cell-Dyn Ruby, Abbott Laboratories, Abbott Park, IL, USA), as instructed by the manufacturers.


Statistical analysis

The values ​​are expressed as mean ± standard deviation. For each of the parameters analyzed pre and post donation, the Student t test was used for paired data with which differences between the beginning and end of the production of erythrocyte package were assessed. 95% was used as a confidence index, considering all probability less than 0.05 significant (p <0.05). The residual white cell count is analyzed after logarithmic transformation.


In this study it was found that the hematological changes tend to decrease significantly, and were evident in hemoglobin (p <0.0001), hematocrit (p <0.0001), leukocytes (p <0.0001), platelets (p <0.0001) lymphocytes (p = 0.0267). On the contrary, the segmented increased (p = 0.037). Monocytes, eosinophils and basophils showed no change after completion of the erythropheresis.

Despite these changes, there were no clinical or symptomatic manifestations that suggested discomfort to the patient or important hematological changes such as anemia or thrombocytopenia. During the regular erythropheresis procedure none of the patients required additional procedures. Nor were (mild or severe) adverse effects seen, only variations in the venous access (one case) and one single donor presented a slower flow compared with other donors.

The socio-demographic characteristics of the study subjects are shown in Table III. Hematological parameters of the globular package is shown in Table IV, which generally had an average of 19 g/dL for hemoglobin, hematocrit 60%, an account 9.6 '109 mL of platelets, and with 31% segmented, 41 % lymphocytes, 0.7% monocytes and 24% eosinophils. Basophils and leukocytes were virtually 0%.

Table III Socio-demographic characteristics of donors
Subject no. 30
Age (range), years 35.27 8.91 ± (19-55)
Sex Male
Height (range), cm 175.3 ± 7.39 (164-190)
Weight (range), kg 86.73 ± 9.73 (71-108)
BMI (range) kg/m2

28.28. ± 2.69 (2325-33.03)
Waist diameter (range), cm 100.61 ± 6.83 (90-115)
Hip diameter (range) cm 101.71 ± 8.2 (85-117)
Waist / hip relationship (range) 0.99 ± 0.05 (0.94-1.16)
Body fat (range), % 25.59 ± 3.88 (1755–34.98)
Lean weight % (range) 6,435.16 ± 629.91 (5, 353.31-8, 027.79)
Systolic blood pressure mmHg (range) 121.83 11.33 ± (100-140)
Diastolic blood pressure mmHg (range) 78.83 ± 7.39 (70-90)
Mean arterial pressure mmHg (range) 100.33 ± 8.8 (85-115)
Smokers, N, (%) 9, (30)
Social drinkers, N (%) 17, (56.6).
Values are presented as the average plus or minus standard deviation, and range in parentheses. No.: number, cm: centimeters, kg: kilograms, BMI: body mass index, m2: square meters, %: percentage, mmHg: millimeters of mercury, N: number

Table IV Hematological measurements in erythrocyte unit
(x 103/µL)
(x 103/µL)
Average 1




28.937 30.334 3.651 2
Max 2
63.4 26.
100 100 20 100 0
Min 1
55.7 1.4 0 0 0 0 0 0
N = 30 30 30 30 30 30 30 30 30
Hb: hemoglobin, HCT: haematocrit, Plaq: platelets, Leu: leukocytes, sec: segmented, Lim: lymphocytes, Mon: monocytes, Eos: eosinophils, Bas: basophils, g: g, dL: deciliter, µL: microliter, %: percentage, sd: standard deviation, Max: maximum value, Min: minimum value N: number

The pre- and post-erythropheresis hematological changes are shown in Figure 1, with a statistically significant decrease in hemoglobin (p <0.0001), hematocrit (p <0.0001), leukocyte (p <0.0001), lymphocytes (p appreciated = 0.0267) and platelet (p <0.0001), but an increase in segmented (p <0.037) when the previous value is compared with the value obtained at the end of the erythropheresis.

Figure 1 Changes in the blood count of both red and white formulations post-erythropheresis. In this panel we can see the changes (all statistically significant) between the pre- and post- erythropheresis measurements (top to bottom and left to right: hemoglobin, hematocrit, leukocytes, lymphocytes, platelets and segmented). Vertical bars show the standard error of the mean and on top of each analyte the P value is shown.

Table V shows pre and post values of the elements of the white formula (monocytes, eosinophils and basophils), which showed no changes during the process.

Table V Cells of the white formula that are unchanged after the erythropheresis procedure
Cells Initial Final P-value
Monocytes (%) 7.588 ± 1.616 8,539 ± 2.975 0.1302
Eosinophils (%) 2,485 ± 1,694 2.372 ± 1.654 0.2222
Basophils (%) 1,166 ± 0.3646 1,170 ± 0.0731 0.9411

The variables reported by the apheresis team during the production of double red are shown in Table II; overall the average duration was 25 minutes, 120 mL of anticoagulant was used with citrate dextrose acid, and 466 mL of saline solution infused to the donors. The processed blood volume averaged 954 mL.


In this study we found that the hematological changes tend to the decrease significantly, and were evident in hemoglobin (p <0.0001), hematocrit (p <0.0001), leukocytes (p <0.0001), platelets (p <0.0001) and lymphocyte (p = 0.0267). On the contrary, we find that the segmented increased (p = 0.037). Monocytes, eosinophils and basophils showed no change after completion of the erythropheresis. Figure 1 shows these changes, the statistical variations shown are evidently results of the process of the erythropheresis and, because these variables are often physiologically highly conserved, minimal changes are sufficient for significant differences to be found. Importantly, no clinical or symptomatic manifestation was found to suggest any discomfort to patient, nor were there found any important hematological changes such as anemia and thrombocytopenia.

During the last two decades, the procedures for obtaining blood and its fractions have improved dramatically in both productivity and the quality of the products obtained, and although erythropheresis is performed worldwide, there is very little information in the world literature in which care for the donor is emphasized. In this study we focused on evaluating hematological changes found in the subject donors in order to improve safety for them, particularly during the production of double red in erythropheresis.

One of the difficulties encountered in this type of study is that erythropheresis is not a standard procedure in blood banks in Mexico, since there are few donors who undergo this procedure because complete donation is preferred to obtain various products useful in the treatment of various hematological blood condition. On the other hand, considering that entry into this study was limited to participants who had not consumed multivitamins or food supplements in the month prior to blood donation, the number of participants fell further. 

All blood donation procedures in principle are subject to changes in hematology of the different donors, for reasons of losses, both of volume and of blood formed elements12 such that changes of hematologic values ​​are to be expected as a result of such losses. However, with the arrival of the apheresis procedure where part of the blood components are returned to the same donor, these hematological changes should be milder.

Due to changes in hemoglobin after erythropheresis, we suggest that donors should get a follow-up appointment and be re-examined at a later date to ensure their welfare. Significant reductions in donors’ hematologic values ​​after erythropheresis and plateletpheresis have been reported, but none have presented clinical issues post-donation.13,14 In an epidemiological study in which they evaluated 939 normal donors, no cases were  reported with thrombocytopenia, but subclinical anemia was found.15 That same work reported that 8.1% of the donors had a post-donation hemoglobin concentration less than 12 g/dL, 15 which, based on its own parameters, the WHO defines as the presence anemia in any normal adult, regardless of gender, when hemoglobin values drop ​​below 12 g/ dL.16

It is well known that erythropheresis devices are getting better when compared with those of earlier generations, since the old ones produced higher hemoglobin and red blood cells losses during apheresis; however, despite this, these losses continue today, and can be attributed to several factors such as blood loss in the empty volume of apheresis kits, and the technique applied, and mechanical hemolysis from the pressure of the equipment itself team.17

In this work we find that there is a significant reduction in hemoglobin, hematocrit, leukocytes and platelets, which is mainly due to the process itself, in cell separator machines and dilution by the infusion of saline and citrate solutions, as has been shown in equivalent procedures.17 In contrast, there is evidence that changes in hemoglobin are negligible in subsequent donations because the donors recover rapidly.18,19

The weakness of this work is that a small sample of subjects (30 donors) was studied and therefore our results, while interesting, are not conclusive on an epidemiological level, so prospective epidemiological studies should be conducted on this aspect, in order to determine the biochemical changes that occur in our donor population after any apheresis procedure.

Based on the results of this study it is recommended that for blood donors undergoing any apheresis procedure with normal low counts before the donation procedure, blood parameters should be determined before and after donating, and similarly pre and post-donation assessments in those subjects with hemoglobin concentrations between 12.5 and 13 g/dL ought also to be stricter. It is also recommended to medically and biochemically examine subjects that have significant drops in hematological parameters post-donation. Donors with significant decreases in their blood parameters must then be reviewed to exclude them from future donations and /or, if necessary, to treat iatrogenic anemia and thrombocytopenia.


Patients undergoing any process of apheresis should be clinically hematologically evaluated routinely before and after donation. The erythropheresis itself causes a significant drop in hemoglobin, hematocrit, leukocytes, platelets and lymphocytes. On the contrary, it increases the amount of segmented.


We thank the National Council of Science and Technology of Mexico (CONACYT, S0008-2009-1-115403) for the partial financial support granted to JMG to perform this work.

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Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.

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