Treating Blood Cells Before Transfusion May Prevent Onset of Pulmonary Hypertension

Treating stored red blood cells with nitric oxide before a transfusion lessens the risk that a patient will develop pulmonary hypertension — a finding that may work to end, or at least substantially lower, a dangerous side effect of blood transfusions.

The study, “Exposure of Stored Packed Erythrocytes to Nitric Oxide Prevents Transfusion-associated Pulmonary Hypertension,” recently appeared in the journal Anesthesiology.

Blood transfusions, most often involving transfusions only of red blood cells, undoubtedly save thousands of lives each year. But when stocks of red blood cells run low, people often receive cells that have been stored for more than 30 days.

The U.S. Food and Drug Administration (FDA) allows for transfusions using blood stored for a maximum of 42 days, but recent studies have shown that cells stored for more than 30 days do not survive equally well, putting patients at risk of reduced oxygen uptake. Importantly, older red blood cells can also trigger lung hypertension.

And the problem is substantial, as about 326,000 people each year receive blood cells stored for more than 30 days in the U.S. alone.

Scientists believe that as red blood cells are stored, hemoglobin that leaks out from broken cells scavenges nitric oxide produced in the blood vessels of the lungs. The gas works to dilate blood vessels, so as its concentrations drop, blood vessels in the lungs constrict, causing the high blood pressure.

Researchers at Massachusetts General Hospital  and Harvard Medical School decided to test if treating stored blood cells with the gas — nitric oxide — could prevent dangerous side effects. Their idea was that the treatment would prevent the cells from sweeping up the nitric oxide once they enter the body.

They used lambs separated into various experimental groups. One group received only fresh blood cells, while another group was transfused with red blood cells that had been stored for 40 days. Some of the stored cells were pre-treated with nitric oxide.

The study found that the treatment allowed more cells to survive; 87 percent of the treated cells remained in the blood after one hour, compared with only 75 percent of non-treated cells. After 24 hours, the difference was 78 percent compared with 73 percent.

Importantly, researchers found a near doubling of lung blood pressure in lambs given untreated stored blood cells. But lung blood pressure in lambs given a transfusion of red blood cells pretreated with nitric oxide did not change and compared to that of lambs that received fresh cells.

Nitric oxide scavenging is one of the mechanisms likely responsible for the risk of pulmonary hypertension, but the research team also explored other factors.

“Extended storage of red blood cells makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” Warren M. Zapol, MD, the study’s senior author and director of the Anesthesia Center for Critical Care Research at Massachusetts General Hospital, said in a press release. “We found that pretreatment with nitric oxide actually rejuvenates red blood cells, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”