By Alice Sardarian
In 1999, James Harrison was awarded the Medal of the Order of Australia for saving millions of children’s lives through his blood plasma donations. Harrison, also known as the “man with the golden arm,” has donated plasma almost every week for the past 60 years, spanning the entire range of donor ages permitted by the Australian Red Cross Blood Service. Plasma is a component of blood that contains nutrients, ions, proteins, and more, not including platelets, leukocytes, and erythrocytes. Plasma donation involves continuously withdrawing blood, separating the red blood cells from the plasma, and then returning the red blood cells back to the donor. According to the Red Cross, plasma may be donated much more frequently than whole blood: donors must wait only 7 days for plasma as opposed to between 8 and 16 weeks for whole blood.
Harrison is amongst a rare group of individuals who have Rho(D) immune globulin present in high concentrations within their plasma. Rho(D), also known as anti-D, is an antibody that results from Rh factor incompatibility. Rh factors are proteins found on blood cell surfaces that correlate to the positive and negative qualities assigned to ABO blood types. When blood cells with Rh factor (+) come into contact with blood cells without it (-), Rh incompatibility occurs and leads to hemolysis, the destruction of Rh factor positive red blood cells. Rh incompatibility, or Rhesus disease, occurs in mothers who are Rh-negative and are pregnant, usually for the second time, with Rh-positive babies. As a result of contact with fetal blood in her first pregnancy, the mother develops antibodies to the Rh factor, such that pregnancy with another Rh-positive baby could lead to the destruction of fetal blood cells as a result of the mother’s immune response. Rhesus disease occurs in approximately 276 of 100,000 births globally, with over 50% of cases remaining untreated and leading to newborn brain damage and more frequently, death.
Rho(D) and other antibodies are a component of the immune system and serve to alert the body of foreign entities in order to prevent harm and mount an attack against the “invader.” In instances when maternal blood comes into contact with fetal blood (fetomaternal hemorrhage)—such as during delivery, obstetric procedures like amniocentesis, and after abdominal trauma—the maternal red blood cells detect fetal red blood cells with Rh factors as foreign, and the maternal immune system consequently proceeds to produce antibodies, causing hemolytic anemia in the fetus or newborn, depending on the time of blood exchange. Anemia occurs as a result of red blood cell destruction and an inability to replace them at an effective rate. As a result, the babies are left with insufficient oxygen-carrying capacity and, in severe cases, fatal oxygen deprivation.
This trauma and suffering can be averted by a vaccine developed in part by the contributions of James Harrison and other similarly generous donors. Rho(D) immune globulin was first developed at Columbia University Irving Medical Center, with the first successful treatment occurring in 1968. A product derived from human plasma, the immune globulin contains antibodies to the D antigen in Rh positive individuals. Functionally, administration of the medicine in a vaccine form suppresses the maternal immune response to Rh positive blood, and is consequently protective when given to a mother prior to (if possible) and after fetomaternal hemorrhage, both prenatally and postnatally. A side effect to the baby may include an allergic reaction; however, the benefits of the drug are overwhelmingly positive, halting fetal blood cell destruction and reducing the levels of bilirubin, a byproduct of this process which can put a newborn at risk of brain damage.
Australia was the first nation to establish a donor program within its borders for the anti-D blood type. It is unclear how certain individuals, like Harrison, have this naturally-occurring blood type. Scientists believe it may be due to an Rh positive blood transfusion they may have received as children, which potentially triggered sensitization, prompting the body to begin producing Rho(D). Harrison received transfusions during an extensive surgery, after which he pledged to donate blood in order to give back to those that saved his life with their donations. Since donors are hard to come by, Rh negative men have actually volunteered to receive Rh positive blood transfusions, in order to produce the rare and healing Rho(D) antibody.
While donors like Harrison have saved many lives and contributed to a major milestone in maternal healthcare, as celebrated at Columbia University Irving School of Medicine’s 50th anniversary of the vaccine’s approval by the FDA, this vaccine is not widely accessible to those in less developed countries. Even while the vaccine is on the World Health Organization’s 21st List of Essential Medicines, rhesus disease still impacts over 150,000 children, primarily in sub-Saharan Africa and South Asia. Greater efforts must be made to ensure global prophylaxis and prevention. Several scientists, including pathologist Dr. Steven Spitalnik of the Columbia Department of Pathology and Cell Biology, recently published a call-to-action in which they highlighted the importance of drug affordability as well as Rh and ABO blood typing during pregnancy, which is rarely completed in those nations suffering the highest mortality rates. Early detection of Rh incompatibility and immediate treatment with Anti-D can prevent alloimmunization in 90% of all cases. Alloimmunization refers to the immune response stimulated by detection of foreign antigens, such as the fetal Rh factor. The publication also notes that the vaccine is not available in China due to governmental drug importation regulations.
Within the United States, there are no established means of ensuring compliance and evaluating the effectiveness of Rho(D) immune globulin administration. A study conducted amongst practicing Obstetrics and Gynecology physicians found that most were well-informed of the treatment practices regarding prophylactic measures, but did not know how to calculate the appropriate dosages when potential cases of fetomaternal hemorrhage arise. Better education and emphasis would certainly improve this knowledge gap, though in the last few months, online calculators have been developed to reduce error rates and improve precision in transfusion medicine; amongst the calculators used by millions worldwide, one was curated specifically for Rho (D) immune globulin dosages.
Remarkably, Rho(D) immune globulin may also be used to treat immune thrombocytopenia, an autoimmune blood disorder, frequently developed after viral infections that range from the flu to HIV. Without treatment, individuals suffer from extensive bleeding as a result of low-platelet count and diminished clotting ability. It is evident that Rho(D) is versatile and effective, providing life-saving measures. With improved access, proper education, and routine blood typing across the globe, rhesus disease morbidity rates will continue to decline, and the full potential of the discovery that resulted in part from James Harrison’s lifetime of donations, will be realized. Mothers and their children will be allowed to live happy and healthy lives, free from the burdens of a completely preventable disease.