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ANAHEIM, CA—Interim results of a large study suggest a blood donor’s genetic background and frequency of donation influence
red blood cell (RBC) storage and stress hemolysis.
Investigators found that donor ethnicity and gender both affected hemolysis, but the effects sometimes differed between storage and stress hemolysis.
Similarly, RBCs from frequent donors were more susceptible to storage and osmotic hemolysis but less susceptible to oxidative hemolysis.
Tamir Kanias, PhD, of the University of Pittsburgh in Pennsylvania, presented these findings at the 2015 AABB Annual Meeting (abstract S73-040A).
“We now know that some donor red cells store very well, and, even after 42 days of storage, there is hardly any hemolysis,” Dr Kanias noted. “[But for] some donors, their red cells are starting to degrade maybe 5 or 6 days after collection.”
With that in mind, Dr Kanias and his colleagues set out to define the genetic and metabolic basis for donor-specific differences in hemolysis in stored RBCs.
They analyzed RBCs collected at 4 centers as part of the REDS-III study. The team took 15 mL of RBCs from fresh units donated for transfusion and stored the cells in transfer bags to measure hemolysis. The transfer bags are miniature versions of the bags used to store RBCs for transfusion.
Dr Kanias presented interim findings in samples from more than 8000 donors. He and his colleagues looked at donor ethnicity, gender, and age. The team also assessed whether subjects were “high-intensity” donors, which was defined as donating RBCs 10 or more times in the previous 24 months without a low-hemoglobin deferral.
The donors’ samples were stored for 39 to 42 days before the investigators assessed hemolysis. They measured end-of-storage hemolysis in unwashed red cells, then washed the RBCs and assessed osmotic hemolysis (Pink test) and oxidative hemolysis (AAPH).
Ethnicity and intensity
Tests showed that RBCs from African American and high-intensity donors (more than 90% of whom were Caucasian) were more susceptible to storage hemolysis than RBCs from the other donor groups analyzed.
RBCs from Caucasian donors and high-intensity donors were susceptible to osmotic hemolysis, while RBCs from African American and Asian donors were more resistant.
“We hypothesize that this [resistance] may be related to some of these donors carrying traits for sickle cell disease or thalassemia,” Dr Kanias said. “Both diseases are known to render red cells more resistant to osmotic hemolysis, but of course, it could be [explained by] new mutations that we don’t know of.”
RBCs from Hispanic donors and African American donors were more susceptible to oxidative hemolysis, but the opposite was true of RBCs from high-intensity donors.
“What was really interesting is that the high-intensity donors that had higher end-of-storage hemolysis and higher susceptibility to osmotic hemolysis actually became more resistant to oxidative hemolysis,” Dr Kanias said.
“It is possible that the lower levels of iron in the red cells of these donors actually protects from oxidative hemolysis. Iron is redox-active, and a lot of the AAPH-induced hemolysis is mediated by iron interactions.”
Group comparisons
Looking at the data another way, the investigators compared samples from Caucasians to samples from the other ethnic groups and the high-intensity donors.
RBCs from African American donors had significantly higher storage hemolysis (P=0.0078), lower osmotic hemolysis (P<0.0001), and higher oxidative hemolysis (P=0.0008) than RBCs from Caucasians.
RBCs from Asians had significantly lower osmotic hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference in storage hemolysis (P=0.69) or oxidative hemolysis (P=0.41) between the 2 groups.
RBCs from Hispanic donors were significantly more susceptible to oxidative hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference between the groups with regard to storage hemolysis (P=0.89) or osmotic hemolysis (P=0.10).
RBCs from high-intensity donors had significantly higher storage hemolysis (P<0.0001) and lower oxidative hemolysis (P<0.0001) than Caucasian RBCs. There was no significant difference in osmotic hemolysis (P=0.84)
Gender and age
As in other studies, Dr Kanias and his colleagues found that RBCs from females hemolyzed significantly less than RBCs from males. This was true for storage hemolysis, osmotic hemolysis, and oxidative hemolysis (P<0.0001 for all).
“Just to note, the gender effect was more dramatic in storage and osmotic rather than oxidative, which suggests that the gender effect is more on the membrane or membrane integrity rather than antioxidant capacity,” Dr Kanias said.
He and his colleagues then looked at donor age and observed the gender effect at every age analyzed (18 to 65+). He noted that hemolysis fluctuated throughout the age groups, so the investigators couldn’t draw any concrete conclusions about hemolysis and donor age.
“One interesting thing to note is that, in all the assays, in young males—like around 20—there’s an increase in hemolysis where there’s a decrease in females,” Dr Kanias said. “This may be related to the effect of sex hormones.”
Genetic modifiers
The investigators also assessed how the 3 hemolytic assays relate to each other and found very weak correlations between them. Pearson correlations were 0.12 between storage and osmotic hemolysis, 0.0041 between storage and oxidative hemolysis, and 0.058 between osmotic and oxidative hemolysis.
“This is kind of cool because it may mean that there is a different genetic modifier affecting each of these phenomena,” Dr Kanias said.
He and his colleagues are now working to identify genetic and metabolic modifiers of hemolysis. 
ANAHEIM, CA—Interim results of a large study suggest a blood donor’s genetic background and frequency of donation influence
red blood cell (RBC) storage and stress hemolysis.
Investigators found that donor ethnicity and gender both affected hemolysis, but the effects sometimes differed between storage and stress hemolysis.
Similarly, RBCs from frequent donors were more susceptible to storage and osmotic hemolysis but less susceptible to oxidative hemolysis.
Tamir Kanias, PhD, of the University of Pittsburgh in Pennsylvania, presented these findings at the 2015 AABB Annual Meeting (abstract S73-040A).
“We now know that some donor red cells store very well, and, even after 42 days of storage, there is hardly any hemolysis,” Dr Kanias noted. “[But for] some donors, their red cells are starting to degrade maybe 5 or 6 days after collection.”
With that in mind, Dr Kanias and his colleagues set out to define the genetic and metabolic basis for donor-specific differences in hemolysis in stored RBCs.
They analyzed RBCs collected at 4 centers as part of the REDS-III study. The team took 15 mL of RBCs from fresh units donated for transfusion and stored the cells in transfer bags to measure hemolysis. The transfer bags are miniature versions of the bags used to store RBCs for transfusion.
Dr Kanias presented interim findings in samples from more than 8000 donors. He and his colleagues looked at donor ethnicity, gender, and age. The team also assessed whether subjects were “high-intensity” donors, which was defined as donating RBCs 10 or more times in the previous 24 months without a low-hemoglobin deferral.
The donors’ samples were stored for 39 to 42 days before the investigators assessed hemolysis. They measured end-of-storage hemolysis in unwashed red cells, then washed the RBCs and assessed osmotic hemolysis (Pink test) and oxidative hemolysis (AAPH).
Ethnicity and intensity
Tests showed that RBCs from African American and high-intensity donors (more than 90% of whom were Caucasian) were more susceptible to storage hemolysis than RBCs from the other donor groups analyzed.
RBCs from Caucasian donors and high-intensity donors were susceptible to osmotic hemolysis, while RBCs from African American and Asian donors were more resistant.
“We hypothesize that this [resistance] may be related to some of these donors carrying traits for sickle cell disease or thalassemia,” Dr Kanias said. “Both diseases are known to render red cells more resistant to osmotic hemolysis, but of course, it could be [explained by] new mutations that we don’t know of.”
RBCs from Hispanic donors and African American donors were more susceptible to oxidative hemolysis, but the opposite was true of RBCs from high-intensity donors.
“What was really interesting is that the high-intensity donors that had higher end-of-storage hemolysis and higher susceptibility to osmotic hemolysis actually became more resistant to oxidative hemolysis,” Dr Kanias said.
“It is possible that the lower levels of iron in the red cells of these donors actually protects from oxidative hemolysis. Iron is redox-active, and a lot of the AAPH-induced hemolysis is mediated by iron interactions.”
Group comparisons
Looking at the data another way, the investigators compared samples from Caucasians to samples from the other ethnic groups and the high-intensity donors.
RBCs from African American donors had significantly higher storage hemolysis (P=0.0078), lower osmotic hemolysis (P<0.0001), and higher oxidative hemolysis (P=0.0008) than RBCs from Caucasians.
RBCs from Asians had significantly lower osmotic hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference in storage hemolysis (P=0.69) or oxidative hemolysis (P=0.41) between the 2 groups.
RBCs from Hispanic donors were significantly more susceptible to oxidative hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference between the groups with regard to storage hemolysis (P=0.89) or osmotic hemolysis (P=0.10).
RBCs from high-intensity donors had significantly higher storage hemolysis (P<0.0001) and lower oxidative hemolysis (P<0.0001) than Caucasian RBCs. There was no significant difference in osmotic hemolysis (P=0.84)
Gender and age
As in other studies, Dr Kanias and his colleagues found that RBCs from females hemolyzed significantly less than RBCs from males. This was true for storage hemolysis, osmotic hemolysis, and oxidative hemolysis (P<0.0001 for all).
“Just to note, the gender effect was more dramatic in storage and osmotic rather than oxidative, which suggests that the gender effect is more on the membrane or membrane integrity rather than antioxidant capacity,” Dr Kanias said.
He and his colleagues then looked at donor age and observed the gender effect at every age analyzed (18 to 65+). He noted that hemolysis fluctuated throughout the age groups, so the investigators couldn’t draw any concrete conclusions about hemolysis and donor age.
“One interesting thing to note is that, in all the assays, in young males—like around 20—there’s an increase in hemolysis where there’s a decrease in females,” Dr Kanias said. “This may be related to the effect of sex hormones.”
Genetic modifiers
The investigators also assessed how the 3 hemolytic assays relate to each other and found very weak correlations between them. Pearson correlations were 0.12 between storage and osmotic hemolysis, 0.0041 between storage and oxidative hemolysis, and 0.058 between osmotic and oxidative hemolysis.
“This is kind of cool because it may mean that there is a different genetic modifier affecting each of these phenomena,” Dr Kanias said.
He and his colleagues are now working to identify genetic and metabolic modifiers of hemolysis.
ANAHEIM, CA—Interim results of a large study suggest a blood donor’s genetic background and frequency of donation influence
red blood cell (RBC) storage and stress hemolysis.
Investigators found that donor ethnicity and gender both affected hemolysis, but the effects sometimes differed between storage and stress hemolysis.
Similarly, RBCs from frequent donors were more susceptible to storage and osmotic hemolysis but less susceptible to oxidative hemolysis.
Tamir Kanias, PhD, of the University of Pittsburgh in Pennsylvania, presented these findings at the 2015 AABB Annual Meeting (abstract S73-040A).
“We now know that some donor red cells store very well, and, even after 42 days of storage, there is hardly any hemolysis,” Dr Kanias noted. “[But for] some donors, their red cells are starting to degrade maybe 5 or 6 days after collection.”
With that in mind, Dr Kanias and his colleagues set out to define the genetic and metabolic basis for donor-specific differences in hemolysis in stored RBCs.
They analyzed RBCs collected at 4 centers as part of the REDS-III study. The team took 15 mL of RBCs from fresh units donated for transfusion and stored the cells in transfer bags to measure hemolysis. The transfer bags are miniature versions of the bags used to store RBCs for transfusion.
Dr Kanias presented interim findings in samples from more than 8000 donors. He and his colleagues looked at donor ethnicity, gender, and age. The team also assessed whether subjects were “high-intensity” donors, which was defined as donating RBCs 10 or more times in the previous 24 months without a low-hemoglobin deferral.
The donors’ samples were stored for 39 to 42 days before the investigators assessed hemolysis. They measured end-of-storage hemolysis in unwashed red cells, then washed the RBCs and assessed osmotic hemolysis (Pink test) and oxidative hemolysis (AAPH).
Ethnicity and intensity
Tests showed that RBCs from African American and high-intensity donors (more than 90% of whom were Caucasian) were more susceptible to storage hemolysis than RBCs from the other donor groups analyzed.
RBCs from Caucasian donors and high-intensity donors were susceptible to osmotic hemolysis, while RBCs from African American and Asian donors were more resistant.
“We hypothesize that this [resistance] may be related to some of these donors carrying traits for sickle cell disease or thalassemia,” Dr Kanias said. “Both diseases are known to render red cells more resistant to osmotic hemolysis, but of course, it could be [explained by] new mutations that we don’t know of.”
RBCs from Hispanic donors and African American donors were more susceptible to oxidative hemolysis, but the opposite was true of RBCs from high-intensity donors.
“What was really interesting is that the high-intensity donors that had higher end-of-storage hemolysis and higher susceptibility to osmotic hemolysis actually became more resistant to oxidative hemolysis,” Dr Kanias said.
“It is possible that the lower levels of iron in the red cells of these donors actually protects from oxidative hemolysis. Iron is redox-active, and a lot of the AAPH-induced hemolysis is mediated by iron interactions.”
Group comparisons
Looking at the data another way, the investigators compared samples from Caucasians to samples from the other ethnic groups and the high-intensity donors.
RBCs from African American donors had significantly higher storage hemolysis (P=0.0078), lower osmotic hemolysis (P<0.0001), and higher oxidative hemolysis (P=0.0008) than RBCs from Caucasians.
RBCs from Asians had significantly lower osmotic hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference in storage hemolysis (P=0.69) or oxidative hemolysis (P=0.41) between the 2 groups.
RBCs from Hispanic donors were significantly more susceptible to oxidative hemolysis (P<0.0001) than Caucasian RBCs, but there was no significant difference between the groups with regard to storage hemolysis (P=0.89) or osmotic hemolysis (P=0.10).
RBCs from high-intensity donors had significantly higher storage hemolysis (P<0.0001) and lower oxidative hemolysis (P<0.0001) than Caucasian RBCs. There was no significant difference in osmotic hemolysis (P=0.84)
Gender and age
As in other studies, Dr Kanias and his colleagues found that RBCs from females hemolyzed significantly less than RBCs from males. This was true for storage hemolysis, osmotic hemolysis, and oxidative hemolysis (P<0.0001 for all).
“Just to note, the gender effect was more dramatic in storage and osmotic rather than oxidative, which suggests that the gender effect is more on the membrane or membrane integrity rather than antioxidant capacity,” Dr Kanias said.
He and his colleagues then looked at donor age and observed the gender effect at every age analyzed (18 to 65+). He noted that hemolysis fluctuated throughout the age groups, so the investigators couldn’t draw any concrete conclusions about hemolysis and donor age.
“One interesting thing to note is that, in all the assays, in young males—like around 20—there’s an increase in hemolysis where there’s a decrease in females,” Dr Kanias said. “This may be related to the effect of sex hormones.”
Genetic modifiers
The investigators also assessed how the 3 hemolytic assays relate to each other and found very weak correlations between them. Pearson correlations were 0.12 between storage and osmotic hemolysis, 0.0041 between storage and oxidative hemolysis, and 0.058 between osmotic and oxidative hemolysis.
“This is kind of cool because it may mean that there is a different genetic modifier affecting each of these phenomena,” Dr Kanias said.
He and his colleagues are now working to identify genetic and metabolic modifiers of hemolysis.