Blood Donation: Separating Myth From Fact

After natural disasters and other tragic events, many people try to help by rushing to the nearest blood donation center. While there’s no denying that many of the victims of tragedies require blood transfusions, the well-intentioned donors aren’t directly helping those people.

“[Public tragedies] raise a lot of awareness about donating after the event, but obviously it was the people who donated in the days before the event whose blood was actually used for victims,” explained Steve Bolton, executive director of the Association of Donor Recruitment Professionals, the educational division of America’s Blood Centers (ABC).

Blood banks can’t survive on what Mr. Bolton called “disaster donations,” which can lead to uneven donation patterns. What’s needed is a stable supply, and that comes with a steady flow of donations over time.

The viability of blood banks is further challenged by restrictions on eligible donors in the United States and blood-banking policies that affect the quality and safety of the nation’s blood supply. ASH Clinical News looked at the history of the blood-banking system and dissected some common blood donation myths and misconceptions.

Blood Bank Backstory

Modern blood banking started with man’s best friend: In the late 1600s, Richard Lower, MD, of Oxford, England, performed the first dog-to-dog blood transfusion.1 Over the next several centuries, scientists made gradual discoveries in transfusion medicine: In 1818, British obstetrician James Blundell, MD, transfused human blood to a dog and learned that human blood should only be transfused to humans; he had some success using transfusions to treat women with postpartum hemorrhage.2 Less than a century later, in 1915, researchers showed that blood treated with a sodium citrate and dextrose solution (an anticoagulant) could be refrigerated and stored for two weeks.

During World War I, Oswald Robertson, MD, a physician with the U.S. Army Medical Corps, introduced blood depots in France; in 1918, he became the first physician to use stored blood for human transfusion.2

The world’s first blood storage center, the London Blood Transfusion Service, was founded by Percy Oliver in 1921. Cook County Hospital in Chicago holds the distinction of being the first such center in the U.S., opened in 1936.2 Eventually, the term “blood bank” took hold globally.

The American Association of Blood Banks was founded in 1947 to set blood bank quality control standards. The following year, the American Red Cross began operating a full-scale blood bank program to collect and distribute blood for medical purposes.

For a few decades, the U.S. blood donation system relied on paid donors to maintain an adequate blood supply, but in 1973, it began operating solely on volunteer donations. Screening for disease and infection became an integral part of that system, and given the restrictions on donations, maintaining a stable blood supply has remained a constant challenge.

More than half of the nation’s blood supply comprises donations from people older than 40 years – and nearly 45 percent comes from people older than 50 years. Blood industry experts are concerned that younger donors are not stepping up to replace the aging donor population. The complicated conversation about who can donate, how much they can donate, and who can receive those donations may also be contributing to this scarcity.

Myth: Fresh Blood Is Better Than Stored

To maximize red blood cell (RBC) supplies, blood banks generally dispense on a first-in, first-out basis, working off the assumption that blood stored up to 42 days (per U.S. Food and Drug Administration [FDA] regulations) will degrade to some extent, but that blood stored for this long is not inherently harmful.

Because blood undergoes several morphologic, biochemical, and physiologic changes over time, some people worry that old blood may lose its efficacy or be deleterious to recipients.

However, according to recent research, the fresh-versus-stored debate is getting stale.

When ASH Clinical News took a deeper look at this issue in February 2016 (“Bad Blood: Is the Debate Over Stored Red Blood Cells Still Relevant?”), experts agreed on two key points. First, findings from major “fresh versus old” blood trials such as ABLE, RECESS, TOTAL, and ARIPI have advanced the hematology community’s understanding of the issue, with each trial demonstrating that stored blood doesn’t affect clinical outcomes. Second, the community lacks a universal definition of what constitutes “fresh” and “old” RBC units, and a standard definition may not even be worth pursuing.3

Results from the 2016 INFORM (Informing Fresh versus Old Red Cell Management) study demonstrated that in-hospital mortality did not differ between patients who received RBC transfusions stored for shorter periods and those who received RBCs stored long-term.4

“The results of the INFORM trial should reassure physicians that the routine use of fresher blood for hospitalized adults that require RBC transfusion is not justified,” lead author Nancy M. Heddle, MSc, an associate professor of pathology and molecular medicine at McMaster University in Ontario, told ASH Clinical News.

While an editorial accompanying the publication of the INFORM results echoed Prof. Heddle’s sentiments, the hematology community expressed great concern with this interpretation of the findings in multiple letters to the editor published in the New England Journal of Medicine.5

Stored RBCs, correspondents argued, undergo “reversible and irreversible lesions” that may affect safety and quality of the products, and the INFORM trial design did not address whether storage length and age of blood matters for outcomes other than death.

More recent studies may offer more clarity as to whether “fresher is better” is simply a myth or a mandate. In the international TRANSFUSE (Standard Issue Transfusion Versus Fresher Red Blood Cell Use in Intensive Care) trial of nearly 5,000 patients, there were no significant differences in 90-day mortality among people who received “fresh” blood (stored for an average of 11.8 days) or older blood (stored for an average of 22.4 days).6

Myth: Moms Can’t Donate

Obviously, men and women are biologically different, including differences in blood composition, such as:7

  • erythrocytes by volume: 45% average in men and 42% in women
  • leukocytes and platelets by volume: 0.4-0.5% in men and 0.2-0.4% in women
  • plasma by volume: 54% in men and 57% in women

Two categories in the Red Cross’s blood-donation eligibility criteria address sex differences between donors. One is “Birth Control,” stating that “Women on oral contraceptives or using other forms of birth control are eligible to donate.”8

The second concerns hemoglobin levels; normal hemoglobin levels for healthy men range between 13.5 and 17.5 g/dL and 12.0 and 15.5 g/dL for healthy women. In 2016, the FDA increased the minimum acceptable hemoglobin level for male blood and platelet donors from 12.5 g/dL to 13.0 g/dL, but even African-American men and women, who sometimes have slightly lower hemoglobin levels, can donate according to the Red Cross.

Eligible women are also required to wait at least six weeks postpartum before blood donation, but as long as the blood groups match and donors meet certain other health criteria (age, weight, general good health), sex isn’t necessarily part of the equation.

A recent study published in JAMA raised questions about whether it should be.9

In the 31,000-participant study, led by Rutger A. Middelburg, PhD, of the Center for Clinical Transfusion Research, Sanquin Research in Leiden, the Netherlands, found that men who received RBC transfusions from women who had ever been pregnant were 13 percent more likely to die during a median of 245 days of follow-up, compared with men who received blood transfusions from male donors.9

Men who received blood transfusions from women who had never been pregnant did not have an increased mortality risk, and neither did women who received blood donations from women who had been pregnant or from male donors.

The authors cautioned that the findings from the retrospective study were “tentative” and required further validation.

Two experts agreed, noting that the results were “provocative,” but shouldn’t signal a change in blood donor selection criteria. Ritchard G. Cable, MD, of the American Red Cross Blood Services, and Gustaf Edgren, MD, PhD, of the Department of Hematology at the Karolinska University Hospital in Stockholm, Sweden, pointed out that “because RBC units from female donors contain about 8 percent less hemoglobin than those from male donors, patients who receive RBC units from female donors may require additional transfusions, [which] may bias the mortality estimates.”10

They also highlighted that mortality differences seemed to increase a year or more after the transfusion, and the observed findings could be related to “an immunologic mechanism based on maternal immunization to paternal antigens” and not necessarily related to differences in donor RBCs or iron physiology.

“The risk was very small, at 1.13,” [a 13% higher risk] stressed Andra H. James, MD, MPH, a maternal-fetal medicine specialist at Duke University Health System in Durham, North Carolina, and an expert spokesperson for the Society of Maternal and Fetal Medicine. “The mechanisms are interesting, but as the authors point out, the blood supply would be inadequate if women who had been pregnant were excluded from donating. Blood is more important than no blood in many situations.”

“The blood supply would be inadequate
if women who had been pregnant
were excluded from donating. Blood is
more important than no blood in many
situations.”

—Andra H. James, MD, MPH

Another issue associated with female blood, and particularly donations from those who have been pregnant, is transfusion-related acute lung injury (TRALI), a complication most commonly caused by white blood cell antibodies present in the plasma component of blood products. When transfused, these antibodies can activate granulocytes, causing plasma to leak into the lungs, and leading to acute pulmonary edema.

“We’ve known for years that blood from women is more likely to result in TRALI, an immediate allergic reaction,” Dr. James explained. “The JAMA study suggests that there are some long-term consequences unrelated to that allergic type response.”

As for what the results may mean for pregnant women who require blood transfusions, including patients with postpartum hemorrhage and associated bleeding disorders, she stated that the results of this study will not “change anything about the nature of the blood that a pregnant woman should receive.

There are special situations, like cases of cytomegalovirus and general precautions that are taken when pregnant women receive a transfusion, but these measures are unrelated to the data provided in this article.”11

Myth: Gay Men’s Blood Is Dangerous

Jesse M. Ehrenfeld, MD, MPH, director of Vanderbilt University Medical Center’s Program for LGBTI Health, seems to be a perfect candidate for a blood donor: He is one half of a monogamous married couple, is young, and is in good health – and he happens to be a professor of anesthesiology, surgery, biomedical informatics, and health policy at Vanderbilt University in Nashville, Tennessee.

But Dr. Ehrenfeld is excluded from giving blood, based on the FDA’s 12-month deferral policy for men who have sex with men (MSM), meaning MSM donors must wait at least 12 months after their last sexual contact with a man before donating.

The ban originated during the HIV/AIDS epidemic of the 1980s. When a 1983 study strongly suggested that AIDS was caused by a bloodborne pathogen, concerns rose worldwide that this unidentified, potentially lethal pathogen could have contaminated the nation’s blood bank supplies. Because HIV/AIDS was more prevalent among gay men than the general population, the FDA issued a blanket, lifetime ban of MSM donations. In 2015, the FDA revised its policy to the present 12-month deferral policy.

“I am ‘Client A.’ I am a gay, married man who is monogamous. Because of my service in the U.S. Navy, I get routinely tested for HIV, and I am HIV-negative. Yet, I am still not able to donate blood,” Dr. Ehrenfeld said. “The FDA policy doesn’t allow for someone like me who is low risk and willing and able to donate blood.”

He was referring to a 2016 New England Journal of Medicine editorial that criticized the “flawed logic” of the 12-month deferral policy. “Client A, a married, monogamous gay man who, along with his husband, has for decades repeatedly tested negative for HIV cannot donate blood,” author Chana Sacks, MD, posited. “However, Client B, a heterosexual man who has had unprotected sex in the past month with multiple women of unknown HIV status is allowed to donate.”12

Client B has the higher chance of introducing HIV into the blood supply, she continued, yet “Client A has been told unequivocally that the medical community sees his blood as unclean, not because of high-risk behavior but because of the sex of his spouse.”

“There were also other groups of people that we now recognize as high-risk donors – prison inmates, institutionalized people – who were serving as paid blood and plasma donors,” added Dr. Ehrenfeld, but these populations were not restricted from donating.

“While we recognize that there needs to be a careful balance between how policies on donor screening are implemented and maintenance of the safety of blood supply,” he said, “we also recognize that it’s important to progress beyond the MSM deferral policy, based on scientific evaluation.”

Indeed, tremendous advances in HIV testing have led to tests that dramatically shorten the “window period” – the time from when an individual is infected with the virus to when a test can detect it – and that have much better sensitivity. The fourth generation of HIV testing offers a near-100 percent sensitivity, and every blood donation is tested for HIV, for a nine- to 14-day window.12

Dr. Sacks noted that, “With updated tests, the risk of HIV transmission has decreased to one in 1.5 million. These advances in blood safety have everything to do with improved testing technology and nothing to do with progress in deferral practices.” They called for revised blood screening policies that rely “on our current best evidence rather than remaining mired in a history of our worst fears.”

“[Disaster donations are] not necessarily
good for the sustainability of the blood
supply. … We hope to educate people to
look beyond the disaster.”

—Steve Bolton, America’s Blood Centers

Dr. Ehrenfeld favors replacing the blanket restriction with individual risk-assessment policies and categorizing MSM into those with low or high risk for HIV. “Under this model, Client A would be deemed a safer candidate for blood donation because he is in a long-term monogamous relationship,” he explained. “This individual assessment policy assesses potential donors strictly based on what is described as ‘risky sexual behavior,’ regardless of their sexual orientation.”

Implementing individual risk assessment is a challenge, though, especially in the large-scale U.S. blood donation system, Dr. Ehrenfeld noted.

For now, the FDA, along with the American Red Cross, ABC, and others are holding firm. “While [HIV] testing has greatly improved, it is not 100 percent effective at detecting infectious diseases in donors with very early infection,” according to an American Red Cross statement. “The FDA selected the 12-month deferral to provide adequate time for the detection of infected individuals.”13

Preparing for the Future

The long-term goal of a stable, reliable blood supply is in sight, if certain shifts in blood donation policies are enacted, according to the experts who spoke with ASH Clinical News.

Mr. Bolton reiterated the importance of public education about the drawbacks of “disaster donations,” which are “not necessarily good for the sustainability of the blood supply. It causes a big surge when a lot of that blood might not necessarily be needed, so blood organizations will act responsibly, and temporarily stop taking donations.” It also has the unintended effect of “turning off” potential volunteer donors. “When a person is turned away from a blood donation, [he or she] tends to not return,” he said. “We hope to educate people to look beyond the disaster, even 12 weeks later, to maintain a steady supply.”

According to Dr. James, the U.S. medical community should adopt extended typing of RBC antigens to prevent Rh antibody antigen mismatches. In Rh incompatibility during pregnancy, if a woman has Rh-negative blood and her baby has Rh-positive blood, the Rh antibodies can cross the placenta and lead to the potentially fatal condition of hemolytic anemia in the infant.14

“This condition, which is entirely preventable, can be devastating to the mother and the unborn baby,” Dr. James emphasized. “The extended typing of RBC antigens, which is now done routinely in other countries such as Australia, could ensure that a pregnant woman, or any woman with childbearing potential requiring transfusion, is not given antigen-mismatched blood.”

Dr. Ehrenfeld emphasized that the growing use of pre-exposure prophylaxis (PrEP) for HIV prevention, in homosexual and heterosexual communities, may affect blood donation policies. A potential blood donor on PrEP who becomes unknowingly infected with HIV – known as a PrEP breakthrough infection – can have suppressed viral replication.15

“That means the viral load is undetectable by the most sensitive HIV test. Failure to seroconvert also has been observed with second-, third-, and fourth-generation testing,” Dr. Ehrenfeld noted. “You can imagine if a person on PrEP was tested during blood donation, the results could be difficult to interpret.”

However, excluding people on PrEP from donating is not necessarily the answer. “PrEP breakthrough infection is a rare circumstance, and the risk is not zero, so that needs to be balanced as policy as developed,” Dr. Ehrenfeld said.

Everyone agreed that balance is key for any change in blood-donation policy, keeping in mind the dual goals of increasing the pool of eligible blood donors in the U.S. and maintaining the safety of anyone who receives donated blood. While questions about the value of recruitment efforts or monetary incentives for repeat donors remain under investigation, clearing up the myths, misconceptions, and uncertainties about who can donate could put the U.S. blood supply on more stable footing. —By Shalmali Pal


References

  1. Fastag E, Varon J, Sternbach G. Richard Lower: the origins of blood transfusion. J Emerg Med. 2013;44:1146-50.
  2. American Association of Blood Banks. “Highlights of transfusion medicine history.” Accessed December 8, 2017, from http://www.aabb.org/tm/Pages/highlights.aspx.
  3. ASH Clinical News. Bad blood: is the debate over stored red blood cells still relevant? Accessed December 4, 2017, from https://www.ashclinicalnews.org/features/bad-blood-is-the-debate-over-stored-red-blood-cells-still-relevant/.
  4. ASH Clinical News. The end of the short- versus long-term blood storage debate? Accessed December 4, 2017, from https://www.ashclinicalnews.org/news/the-end-of-the-short-versus-long-term-blood-storage-debate/.
  5. Correspondence. Short-term versus long-term blood storage. N Engl J Med. 2017;376:1091-94.
  6. Cooper DJ, McQuilten ZK, Nichol A. Age of red cells for transfusion and outcomes in critically ill adults. N Engl J Med. 2017;377:1858-67.
  7. University of Sydney. “Gender differences in blood content, March 17, 2016.” Accessed December 5, 2017, from http://sydney.edu.au/science/biology/learning/blood_composition/Gender.shtml.
  8. American Red Cross. “Eligibility requirements.” Accessed December 3, 2017, from https://www.redcrossblood.org/donating-blood/eligibility-requirements.
  9. Caram-Deelder C, Kreuger AL, Evers D, et al. Association of blood transfusion from female donors with and without a history of pregnancy with mortality among male and female transfusion recipients. JAMA. 2017;318:1471-8.
  10. Cable RG, Edgren G. Blood transfusions from previously pregnant women and mortality: interpreting the evidence. JAMA. 2017;318:1445-7.
  11. James AH, Cooper DL, Paidas MJ. A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders. Int J Womens Health. 2017;9:477-85.
  12. Sacks CA, Goldstein RH, Walensky RP. Rethinking the ban – the U.S. blood supply and men who have sex with men. N Engl J Med. 2017;376:174-7.
  13. American Red Cross. “Joint Statement: FDA Revised MSM Blood Donation Policy. December 16, 2016.” Accessed December 5, 2017, from http://www.redcross.org/news/press-release/lp/Joint-Statement-FDA-Revised-MSM-Blood-Donation-Policy.
  14. National Heart, Lung, and Blood Institute. “What is Rh incompatibility?, January 1, 2011.” Accessed December 4, 2017, from https://www.nhlbi.nih.gov/health-topics/rh-incompatibility.
  15. Seed CR, Yang H, Lee JF. Blood safety implications of donors using HIV pre-exposure prophylaxis. Vox Sang. 2017;112:473-6.

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