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The impact of apheresis on iron stores
Plasma Ther Transfus Technol 19Wj 9:343-346 Printed
in Great
Britain.
All rights
reserved
Copyright
0278-6222188 $3.00+0.00 1988 Pergamon Press plc
0
The Impact of Apheresis on Iron Stores Vanessa J. Martlew, MB, MRCP, MRCPath H. M. Waters, MSc, FIMLS J. E. Howarth BSc, FIMLS, DMLM
n Monthly plasmapheresis of volunteer donors was introduced at the Manchester Apheresis Centre late in 1985. Serum ferritin was measured at the outset and after 12 months regular donation to monitor iron stores. In a cohort of 100 male and 86 female blood donors it was found that both groups had mean serum ferritins lower than non-donor controls. A year after conversion to monthly plasma donation the female donors were found to increase mean serum ferritin almost to that of the control subjects while a much smaller rise was observed in their male counterparts. It was concluded that plasmapheresis is conservative of iron stores, and the benefits are apparent earlier in females. n
Donors within the United Kingdom Transfusion Services. A study of serum ferritin levels from donors after the first 12 months of plasmapheresis has been undertaken to test the validity of this assumption. METHODS Volunteers for plasmapheresis were recruited from the panel of established blood donors; 100 males and 86 females between 18 and 50 years of age were selected who had easy access to the Regional Apheresis Centre which is near the centre of Manchester. Many were employed in the City Centre and all had made at least one previous donation of whole blood. They were chosen medically according to the current Guidelines for Selection of Plasmapheresis Donors within the Transfusion Service of Eng land and Wales. Since their proposed attendance was both regular and frequent, an introductory visit was arranged for each to provide informed written consent for enrolment on the panel. A formal medical examination was carried out during which blood was obtained for certain baseline investigations which included a full blood count performed on a Coulter S Plus II (Coulter Electronics Ltd) and serum ferritin by a two-site solidphase enzyme-linked immunosorbent assay (ELISAJ.3 The serum ferritin was repeated annually as a routine and the full blood
Whereas donors of whole blood should contribute only 2 or 3 times a year a schedule of monthly plasma donation was established in the absence of red cell loss. This recommendation was based on the premise that plasmapheresis would be conservative of iron stores, according to the 1985 Guidelines for the Use of Automated Plasmapheresis of Volunteer
From the Regional Transfusion Centre, Plymouth Grove, Manchester, Ml3 9LL and University De artment of Clinical Haematology, Manchester Royal In E rmary, Oxford Road, Manchester, U.K. Received 6/88; Accepted 9/88. 343
344
Plasma Ther Transfis Technol
Vol. 9, No. 4
closely observed, but donations continued to be collected at the usual time intervals (i.e. every 4 weeks) provided the haemoglobin was maintained. Since the ferritin results were not normally distributed they were submitted to a Wilcoxon signed rank test of paired data.
count checked every 3 months unless indicated clinically. A capillary haemoglobin was estimated before each donation using a Hemacue calorimeter (Clandon Scientific Ltd). A final check on the volunteer’s health was made in consultation with the appropriate general practitioner. Provided 3 months had elapsed since their last donation of whole blood, initial plasmapheresis was undertaken at least 1 month after the first attendance to ensure completion of all investigations. Donations were collected from the 86 females whose haemoglobin was in excess of 12.0 g/dL and from the 100 males with haemoglobin levels exceeding 13.0 g/dL on the Hemacue. Plasmapheresis was carried out by centrifugation using the Haemonetics Plasma Collection System and the volume of plasma varied between 500 and 600 mL according to the weight of the subject. Red cell loss was approximately 50 mL including specimen collection. A group of 158 control subjects were identified as 79 males and 79 females prior to their first blood donation, and serum ferritins were performed on each group to establish the adult reference range. The minimum values established were 5.5 pg/L for females and 10 pgg/L for males. Those donors with subnormal results were Table 2.
RESULTS Serum ferritin values for the control group of non-donors are expressed in Table 1. The results of serum ferritins in established blood donors before plasmapheresis and after 12 months’ plasma donation are represented respectively for males and females in Tables 2 and 3. The non-donor male controls have a mean ferritin of 72.8 &L and their female counterparts 25.2 ug/L. Blood donors exhibit a lower mean ferritin although this value of 29.2 cLg/Lfor males and 14.9 ug/L for females remains within
Table 1.
Non-donor Number
Male Female
79 79
Controls Ferritin (pg/L) Range Mean
l&277 5.5-66.5
72.8 25.2
SD 49.7 15.3
SD = standard deviation.
Male Donors Number
Pre-apheresis
Ferritin (pg/L) Range Mean
SD
100
4-84
29.2
20.57
100
4.9-119
33.9
24.326
t (Wilcoxon text) 1913 (S)
After 12 months
apheresis
SD = standard deviation.
Table 3.
S = significant at 5% level.
Female Donors Number
Pre-apheresis
Ferritin (pg/L) Range Mean
SD
86
4- 50.2
14.9
10.7
86
4-119
22.9
20.1
t (Wilcoxon test) 1067.5 (S)
After 12 months
apheresis
SD = standard deviation.
S = significant at 5% level.
0NON-DO 1I-l Apheresis and Iron Stores
COWARlSON BLOOD AH)
MEAN FERRITI /@’
So 70 6
OF FERRITINS IN
PLASMA
DONORS
CONTROL
q PLASMA DONOR $ q BLOOD DONOR +
50 40
$
Means recorded
after 12 months plmmm donation
t Means recorded after al least 2 whole blood donations
Figure 1. Comparison of ferritins in blood and plasma donors.
the reference range. After a year of monthly plasmapheresis, there is a significant rise (P <0.05) in mean ferritin values for both sexes, although the relative increase is greater in the female group. The differences between the spaced mean ferritin values expressed in Tables l-3 are illustrated in Fig. 1. The histogram shows clearly that Manchester blood donors of both sexes have reduced serum ferritins. This is more striking in the male population whose mean nondonor control ferritin level is almost three times that of the female. After a year’s plasmapheresis the value of the mean female donor ferritin approaches that of the non-donor control, while the male mean remains near to the lower end of the reference range. DISCUSSION The population studied made their donations in the centre of Manchester. The majority attended during business hours since their places of work were convenient to collection sessions. There was, therefore, a preponderance of individuals employed in sedentary occupations although many enjoyed sport in their leisure. The non-donor controls group mean ferritin is rather lower than the published data of Walters et al.4 based on subjects in the Cardiff area in the 1970s.
345
However, the method used in the present study3 employed a substrate ferritin of human liver origin supplied by NIBSC (80/602) together with different methodology and calibration procedures from those of the Cardiff group.5 In Manchester regular blood donation was found to decrease the mean serum ferritin for both sexes, and in the case of the females to the lower limit of the reference range. When the donation of whole blood ceases in favour of monthly plasmapheresis the effects on the iron stores may be assessed by measurement of serum ferritin.6 After 12 months’ plasma donation there was a significant increase in mean ferritins in both sexes. The mean value for the serum ferritin level in the female donor group approximated to that of the control group. In contrast, the mean value for the male donor group had risen to only half the value of the control group mean. Both sexes were submitted to identical blood sampling prior to each donation, with no evident source of additional red cell loss in the male. The majority of females were premenopausal with a regular source of blood loss at menstruation and many were multipartus. It is recognized in pregnancy that large amounts of iron may be transferred to the foetus in a short space of time and that the foetus is invariably iron replete at the expense of its mother.7 In the absence of lactation or excessive blood loss at parturition, the iron reserves may be restored 6 weeks after delivery, and regular menstruation demands a higher daily iron requirement. Since no such physiological mechanisms exist in the male there may be a slower response to discontinued intermittent iron loss in the form of whole blood donation. This hypothesis might be confirmed by iron absorption studies, but the use of isotopes in volunteer donors is not considered ethical in this situation. Preliminary studies of serum ferritins in a small group of the same individuals after 2 years’ plasmapheresis suggest that the males exhibit a further increase in serum ferritin, whereas the females remain sta-
346
Plasma Ther Transfus Technol
Vol. 9, No. 4
tic from the point of view of their iron stores. It would appear that plasmapheresis is positively beneficial to the female volunteers. It remains to be seen whether established plasma donors of either sex will reach the mean ferritins of non-donor controls in the absence of red cell loss, and this will form the basis of a further communication. This study confirms the hypothesis that regular plasmapheresis at monthly intervals is conservative of iron stores. These were assessed by serum ferritins measured after the donation of 6L of plasma in a year. The apheresis procedure includes a complete return of red cells to the donor and is not therefore associated with iron loss.
REFERENCES 1. Robinson EAE: Plasma and blood component procurement. Plasma Ther Transfus Technol 1987; 8:193-203.
2. Hansard: Adjournment debate, House of Commons Official Report, 1980, December 15. 3. Waters HM: Serum ferritin and its enzyme-immunoassay. MSc Thesis, University of Manchester, 1985. 4. Walters GO, Miller FM, Worwood M: Serum ferritin concentrations and iron stores in normal subjects. 1 Clin Path01 1973; 26:770-772.
5. Addison GM, Beamish MR, Hales CN et
al.: An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. 1 Clin Path01 1972; 251326-329. 6. Strandberg-Pederson N, Morling N: Iron stores in blood donors evaluated by serum ferritin. ScandJHaemato11978j 20:70-76. 7. Rios E, Lipschitz DA, Cook JD, Smith N: Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin. Pediatrics 1975; 55:694699.
in Great
Britain.
All rights
reserved
Copyright
0278-6222188 $3.00+0.00 1988 Pergamon Press plc
0
The Impact of Apheresis on Iron Stores Vanessa J. Martlew, MB, MRCP, MRCPath H. M. Waters, MSc, FIMLS J. E. Howarth BSc, FIMLS, DMLM
n Monthly plasmapheresis of volunteer donors was introduced at the Manchester Apheresis Centre late in 1985. Serum ferritin was measured at the outset and after 12 months regular donation to monitor iron stores. In a cohort of 100 male and 86 female blood donors it was found that both groups had mean serum ferritins lower than non-donor controls. A year after conversion to monthly plasma donation the female donors were found to increase mean serum ferritin almost to that of the control subjects while a much smaller rise was observed in their male counterparts. It was concluded that plasmapheresis is conservative of iron stores, and the benefits are apparent earlier in females. n
Donors within the United Kingdom Transfusion Services. A study of serum ferritin levels from donors after the first 12 months of plasmapheresis has been undertaken to test the validity of this assumption. METHODS Volunteers for plasmapheresis were recruited from the panel of established blood donors; 100 males and 86 females between 18 and 50 years of age were selected who had easy access to the Regional Apheresis Centre which is near the centre of Manchester. Many were employed in the City Centre and all had made at least one previous donation of whole blood. They were chosen medically according to the current Guidelines for Selection of Plasmapheresis Donors within the Transfusion Service of Eng land and Wales. Since their proposed attendance was both regular and frequent, an introductory visit was arranged for each to provide informed written consent for enrolment on the panel. A formal medical examination was carried out during which blood was obtained for certain baseline investigations which included a full blood count performed on a Coulter S Plus II (Coulter Electronics Ltd) and serum ferritin by a two-site solidphase enzyme-linked immunosorbent assay (ELISAJ.3 The serum ferritin was repeated annually as a routine and the full blood
Whereas donors of whole blood should contribute only 2 or 3 times a year a schedule of monthly plasma donation was established in the absence of red cell loss. This recommendation was based on the premise that plasmapheresis would be conservative of iron stores, according to the 1985 Guidelines for the Use of Automated Plasmapheresis of Volunteer
From the Regional Transfusion Centre, Plymouth Grove, Manchester, Ml3 9LL and University De artment of Clinical Haematology, Manchester Royal In E rmary, Oxford Road, Manchester, U.K. Received 6/88; Accepted 9/88. 343
344
Plasma Ther Transfis Technol
Vol. 9, No. 4
closely observed, but donations continued to be collected at the usual time intervals (i.e. every 4 weeks) provided the haemoglobin was maintained. Since the ferritin results were not normally distributed they were submitted to a Wilcoxon signed rank test of paired data.
count checked every 3 months unless indicated clinically. A capillary haemoglobin was estimated before each donation using a Hemacue calorimeter (Clandon Scientific Ltd). A final check on the volunteer’s health was made in consultation with the appropriate general practitioner. Provided 3 months had elapsed since their last donation of whole blood, initial plasmapheresis was undertaken at least 1 month after the first attendance to ensure completion of all investigations. Donations were collected from the 86 females whose haemoglobin was in excess of 12.0 g/dL and from the 100 males with haemoglobin levels exceeding 13.0 g/dL on the Hemacue. Plasmapheresis was carried out by centrifugation using the Haemonetics Plasma Collection System and the volume of plasma varied between 500 and 600 mL according to the weight of the subject. Red cell loss was approximately 50 mL including specimen collection. A group of 158 control subjects were identified as 79 males and 79 females prior to their first blood donation, and serum ferritins were performed on each group to establish the adult reference range. The minimum values established were 5.5 pg/L for females and 10 pgg/L for males. Those donors with subnormal results were Table 2.
RESULTS Serum ferritin values for the control group of non-donors are expressed in Table 1. The results of serum ferritins in established blood donors before plasmapheresis and after 12 months’ plasma donation are represented respectively for males and females in Tables 2 and 3. The non-donor male controls have a mean ferritin of 72.8 &L and their female counterparts 25.2 ug/L. Blood donors exhibit a lower mean ferritin although this value of 29.2 cLg/Lfor males and 14.9 ug/L for females remains within
Table 1.
Non-donor Number
Male Female
79 79
Controls Ferritin (pg/L) Range Mean
l&277 5.5-66.5
72.8 25.2
SD 49.7 15.3
SD = standard deviation.
Male Donors Number
Pre-apheresis
Ferritin (pg/L) Range Mean
SD
100
4-84
29.2
20.57
100
4.9-119
33.9
24.326
t (Wilcoxon text) 1913 (S)
After 12 months
apheresis
SD = standard deviation.
Table 3.
S = significant at 5% level.
Female Donors Number
Pre-apheresis
Ferritin (pg/L) Range Mean
SD
86
4- 50.2
14.9
10.7
86
4-119
22.9
20.1
t (Wilcoxon test) 1067.5 (S)
After 12 months
apheresis
SD = standard deviation.
S = significant at 5% level.
0NON-DO 1I-l Apheresis and Iron Stores
COWARlSON BLOOD AH)
MEAN FERRITI /@’
So 70 6
OF FERRITINS IN
PLASMA
DONORS
CONTROL
q PLASMA DONOR $ q BLOOD DONOR +
50 40
$
Means recorded
after 12 months plmmm donation
t Means recorded after al least 2 whole blood donations
Figure 1. Comparison of ferritins in blood and plasma donors.
the reference range. After a year of monthly plasmapheresis, there is a significant rise (P <0.05) in mean ferritin values for both sexes, although the relative increase is greater in the female group. The differences between the spaced mean ferritin values expressed in Tables l-3 are illustrated in Fig. 1. The histogram shows clearly that Manchester blood donors of both sexes have reduced serum ferritins. This is more striking in the male population whose mean nondonor control ferritin level is almost three times that of the female. After a year’s plasmapheresis the value of the mean female donor ferritin approaches that of the non-donor control, while the male mean remains near to the lower end of the reference range. DISCUSSION The population studied made their donations in the centre of Manchester. The majority attended during business hours since their places of work were convenient to collection sessions. There was, therefore, a preponderance of individuals employed in sedentary occupations although many enjoyed sport in their leisure. The non-donor controls group mean ferritin is rather lower than the published data of Walters et al.4 based on subjects in the Cardiff area in the 1970s.
345
However, the method used in the present study3 employed a substrate ferritin of human liver origin supplied by NIBSC (80/602) together with different methodology and calibration procedures from those of the Cardiff group.5 In Manchester regular blood donation was found to decrease the mean serum ferritin for both sexes, and in the case of the females to the lower limit of the reference range. When the donation of whole blood ceases in favour of monthly plasmapheresis the effects on the iron stores may be assessed by measurement of serum ferritin.6 After 12 months’ plasma donation there was a significant increase in mean ferritins in both sexes. The mean value for the serum ferritin level in the female donor group approximated to that of the control group. In contrast, the mean value for the male donor group had risen to only half the value of the control group mean. Both sexes were submitted to identical blood sampling prior to each donation, with no evident source of additional red cell loss in the male. The majority of females were premenopausal with a regular source of blood loss at menstruation and many were multipartus. It is recognized in pregnancy that large amounts of iron may be transferred to the foetus in a short space of time and that the foetus is invariably iron replete at the expense of its mother.7 In the absence of lactation or excessive blood loss at parturition, the iron reserves may be restored 6 weeks after delivery, and regular menstruation demands a higher daily iron requirement. Since no such physiological mechanisms exist in the male there may be a slower response to discontinued intermittent iron loss in the form of whole blood donation. This hypothesis might be confirmed by iron absorption studies, but the use of isotopes in volunteer donors is not considered ethical in this situation. Preliminary studies of serum ferritins in a small group of the same individuals after 2 years’ plasmapheresis suggest that the males exhibit a further increase in serum ferritin, whereas the females remain sta-
346
Plasma Ther Transfus Technol
Vol. 9, No. 4
tic from the point of view of their iron stores. It would appear that plasmapheresis is positively beneficial to the female volunteers. It remains to be seen whether established plasma donors of either sex will reach the mean ferritins of non-donor controls in the absence of red cell loss, and this will form the basis of a further communication. This study confirms the hypothesis that regular plasmapheresis at monthly intervals is conservative of iron stores. These were assessed by serum ferritins measured after the donation of 6L of plasma in a year. The apheresis procedure includes a complete return of red cells to the donor and is not therefore associated with iron loss.
REFERENCES 1. Robinson EAE: Plasma and blood component procurement. Plasma Ther Transfus Technol 1987; 8:193-203.
2. Hansard: Adjournment debate, House of Commons Official Report, 1980, December 15. 3. Waters HM: Serum ferritin and its enzyme-immunoassay. MSc Thesis, University of Manchester, 1985. 4. Walters GO, Miller FM, Worwood M: Serum ferritin concentrations and iron stores in normal subjects. 1 Clin Path01 1973; 26:770-772.
5. Addison GM, Beamish MR, Hales CN et
al.: An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. 1 Clin Path01 1972; 251326-329. 6. Strandberg-Pederson N, Morling N: Iron stores in blood donors evaluated by serum ferritin. ScandJHaemato11978j 20:70-76. 7. Rios E, Lipschitz DA, Cook JD, Smith N: Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin. Pediatrics 1975; 55:694699.