Golden blood: the rare and mysterious Rh-null blood type

Let's take a look at everything you need to know about the “golden blood” and what it means for those who have it.

Understanding the genetics of Rh-null blood

Rh-null blood derives from a genetic mutation in the RHD and RHCE genes, which produce Rh antigens. This mutation is inherited in an autosomal recessive pattern, meaning a person must inherit two copies of the mutated gene (one from each parent) to have Rh-null blood. 

Rh antigens are protein molecules on the surface of red blood cells that help to maintain the membranes and overall structure of red blood cells. Scientists believe they may also be involved in the transportation of substances in and out of the cells, such as the removal of blood ammonia (a waste product generated during the breakdown of proteins in the digestion process).

There are hundreds of different antigens, and they fall into 33 recognized blood group systems, including the Rh system. While the Rh system consists of 50 defined blood group antigens, the five main ones are D, C, c, E, and e. These are considered important in evaluating blood compatibility when planning a blood transfusion. 

The Rh factor itself is determined by the absence of the presence of the D antigen, which produces the strongest immune reactions when blood with and without the D antigen are mixed. This means it is most likely to cause a transfusion reaction in the recipient.

Most people have the D antigen in their blood and, therefore, are considered to be Rh-positive. People who do not have the D antigen are considered to be Rh-negative. 

People who do not have any kind of Rh antigen are considered to be Rh-null.

Historical discovery and medical significance of Rh-null blood

Rh-null blood was first discovered in an Aboriginal Australian woman in 1961. Her blood hadn’t reacted to Rh antisera, and therefore, it was described as blood with no detectable Rh antigens. The term “Rh-null” was first used by Italian geneticist Ruggero Ceppellini and adopted by other physicians who started finding people with this type of blood. 

The second case of Rh-null blood was discovered by physician Philip Levine and his team in 1964.  As time went by, a few other cases were detected around the world, mostly during routine Rh phenotyping, preparation of blood transfusions, and investigation of certain blood disorders. 

Prevalence and distribution of Rh null blood worldwide

Cases of Rh deficiency, or Rh-null blood, are scarce (fewer than 50) and have been found in different countries and continents, such as:

• Japan (reported in 1987)

• Spain (reported in 1992)

• Brazil (reported in 2015)

• Iran (reported in 2018)

• Colombia (reported in 2021)

• China (reported in 2022) 

In some cases, the Rh-null blood runs in families, which makes sense due to its genetic component. 

There is also some evidence to suggest that consanguineous marriages (marriages between individuals who are second cousins or closer) can increase the likelihood of having the gene mutation that causes Rh-null blood. 

Rh-null blood and autoimmune hemolytic anemia

Given that Rh antigens help maintain the shape of red blood cells, people with Rh-null blood can have abnormally-shaped red blood cells, which can trigger an autoimmune response. 

This means the person’s immune system can attack and destroy these abnormal-shaped red blood cells. As a result, the person may develop anemia, a condition in which the body has a low count of healthy red blood cells.

There are various types of anemia, but in this case, it is generally called Autoimmune Hemolytic Anemia (AIHA) because the destruction of red blood cells (a process called hemolysis) is caused by an autoimmune reaction. 

Rh-null blood and pregnancy 

Women with Rh-null blood must be extra cautious during pregnancy because if the baby inherits the gene for Rh-positive blood from the father, he or she is at risk of getting the hemolytic disease of the fetus and newborn (HDFN – also known as Rhesus disease). 

This is a condition that occurs when the mother's immune system reacts against the Rh antigens in the fetus's red blood cells. As a result, the newborn can have anemia, severe jaundice, swelling (edema), an enlarged liver or spleen, etc. In severe cases, HDFN can even cause stillbirth or neonatal death.

To prevent this, pregnant women with Rh-null blood (as well as those with Rh-negative blood) must have a dose of Rh immunoglobulin, a medicine that prevents the mother's immune system from reacting to the baby's Rh antigens. They must also receive regular prenatal care to detect HDFN early and prevent complications. 

If they don’t receive the medication in time and they develop antibodies for Rh antigens, then any future babies will be at risk of developing HDFN. 

Challenges and opportunities of Rh-null blood donation and transfusion

People with Rh-null blood do not have any type of Rh antigens; therefore, they can’t receive blood from a person who has them (this includes people with Rh-negative blood). If they do, they can develop an adverse immune reaction called Hemolytic Transfusion Reaction (HTR). 

Someone with HTR may experience high fevers, low blood pressure, shortness of breath, kidney failure, and other life-threatening complications. This is why people with Rh-null blood rely on banking their own blood or on the very small network of other Rh-null blood donors if they need a blood transfusion. 

Since there are not many of these Rh-null blood donors (about nine in the whole world), and people with Rh-null blood are at a higher risk of developing anemia or other blood disorders, it is unsafe for them to donate their blood on a frequent basis.

Rh-null blood in blood banks is very scarce and is not only used when people with Rh-null blood need a transfusion but also when someone in need of a transfusion has antibodies against certain Rh antigens or blood types. In these cases, transfusing Rh-null blood can be a safe and effective option to avoid a transfusion reaction. 

To date, Rh-null blood remains an important area of study in the field of hematology and highlights the importance of blood donation and the search for compatible blood types.