Hundreds of cases around the world found contamination in plasma dispensing machines, according to ZEIT research. Tiny particles could have been transferred to donors. With what consequences is not researched. The machines are still in use in Germany. Were and are plasma donors at risk? First of all: All this has nothing to do with blood donation.

What did the research reveal?

DIE ZEIT and seven international media partners evaluated internal documents from the US company Haemonetics, which they received from whistleblowers. The company is one of the world market leaders in the blood processing industry and builds, among other things, plasma dispensing machines. According to the documents, certain of these devices have had problems with particle contamination for years. They settle in the centrifuge inserts or are found in the blood plasma obtained.

Since 2005, more than 600 cases in connection with particles have appeared in the documents, 56 of them in Germany. According to Haemonetics, particles rarely occur - only about 0.0006 percent of all donation procedures were reported. The devices have not been used in France since 2018, but they are still in operation in many countries - including here. It cannot be ruled out that particles have been transferred to plasma donors. On request, Haemonetics says that the parts used in the machines are "safe and non-toxic to people".

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What is blood plasma?

Plasma is the liquid part of the blood. It looks pale yellow and contains no cells. It mainly consists of water, but it also contains important proteins. Some are important for blood clotting, others for immune defense or to keep the pH of the blood constant. The proteins are also the main reason why plasma is a sought-after raw material in the pharmaceutical industry.

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What is plasma used for?

Coagulation factor preparations, for example, are made from plasma and are used to treat people suffering from a blood disorder. The protein fibrin is used in surgery, for example, as an adhesive to close wounds. Doctors use albumin after serious injuries or burns when people have lost a lot of protein and fluids. And antibodies derived from plasma can help people who suffer from an immune deficiency. In addition, plasma is also frozen and can be kept for about two years. Such frozen fresh plasma is transfused, for example, to patients who have lost a lot of blood due to an accident.

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What role does it play for Covid-19?

There is hope that the plasma from Covid-19-recovered people might help corona infected people. The idea behind it: Anyone who survives an infection with Sars-CoV-2 then has tailor-made antibodies against the virus in the blood. They could support the immune system in the fight against the pathogen. So far, however, there is still little scientific evidence for the effect of the method. A controlled study with 103 seriously ill patients in China was terminated prematurely because there was no benefit ( JAMA : Li et al., 2020). In Germany, initial studies are also underway on less sick patients. Only a few centers in Germany are currently allowed to collect such convalescent plasma. 

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How does a plasma donation work?

Whenever you donate plasma (also called plasmapheresis), whole blood is drawn. A special device separates the plasma from the solid components of the blood. This happens in several cycles. While the plasma is being collected, the solid components - i.e. red and white blood cells and platelets - still flow back into the donor's body during the donation. A plasma donation usually takes about 30 to 45 minutes.

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What distinguishes plasma from blood donation?

This article is the result of international research by the Signals Network and its call to whistleblowers to make grievances public. ZEIT cooperated with "El Mundo" (Spain), "Mediapart", "bastamag" and "Radio France" (France), "Miami Herald" (USA), "NRC" (Netherlands) and "Il Fatto Quotidiano" ( Italy). © Matthias Schütte for ZEIT graphics

If someone donates blood, whole blood is collected, i.e. blood cells and plasma. The donors get nothing back into the body. Therefore, blood donors are not affected by possible contamination in plasma machines. Whole blood is separated into its components after the donation and plasma is also obtained from it. According to the Robert Koch Institute (RKI), more than 2.2 million people in Germany donated whole blood and around 217,000 people in 2018. 

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Who can become a plasma donor?

In principle, plasma can be donated by anyone who is healthy, between 18 and 68 years old and who weighs at least 50 kilograms (Guideline on Hemotherapy, PDF). However, there are numerous reasons why people are temporarily or permanently not allowed to donate plasma. Before the first donation and every fifteenth plasma donation, a doctor examines whether you are suitable as a donor. Whoever is allowed to donate, depending on their body weight, 650, 750 or 850 milliliters of plasma are taken from each donation. Women and men can donate up to 60 times within twelve months, but there must be at least three days between two dates. In contrast to blood donation, you can donate plasma so often because blood cells are not removed from the body. The body replicates the plasma proteins much faster.

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How much money do you get?

In Germany there is no payment for donating plasma. However, many blood and plasma donation services offer an allowance. Depending on the center, it can amount to around 20 to 40 euros per donation and is tax-free. Sometimes you get vouchers instead of money.

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How safe is that for plasma donors?

"In Germany, plasma donations are considered safe if the donors are medically monitored between donations," says Peter Hellstern, transfusion doctor at the Hemostasis Thrombosis Center Zurich and co-author of the Hemotherapy Guideline. The limiting factor in plasma donation is that some proteins can no longer be replicated quickly enough by the body if you donate very often. Above all, it is about immunoglobulin G. These are antibodies that are important for the immune system. If their blood concentration falls below a certain critical value, the donor must wait two weeks longer until the next donation. If the value is three times too low, the person is permanently excluded from the plasma donation, because the risk of infection is then considered to be increased.

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Are there any side effects?

Plasma donation is generally well tolerated. In addition to bruises at the puncture sites of the needles, the most common side effect of donating plasma is that blood pressure can drop ( Transfusion Medicine and Hemotherapy : Diekamp et al., 2014). This is because volume is removed from the body. Some people get a little dizzy, but usually helps to put up legs or have a drink.

In a few cases, a citrate reaction can also occur. It is triggered by a citrate solution that is designed to prevent the blood from clotting in the tube during the donation. Parts of the solution get into the donor's body when he gets his cells back. This can cause arms and hands to tingle or have a metallic taste. However, this is temporary because the body breaks down the citrate. Serious side effects are extremely rare when donating plasma. Hellstern says: "The risks of donating plasma are very low if everything is done correctly, if people donate too often and the machines are safe."

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What is the problem with the particles?

According to ZEIT's research, small and very small components can come loose and come into contact with certain plasma collection machines from the US company Haemonetics in the event of malfunction during donation. Some of the particles are abrasion from a swivel in certain centrifuge inserts, where the machines spin the donors' blood to collect plasma. In some cases, particles were so large that they could be seen with the naked eye, for example in plasma bags. However, invisible micro- and possibly nanoparticles could also arise, as stated by an expert report from 2017. These particles would be so small that they could overcome the protective filters in the tubes that are supposed to keep foreign objects out, and thus possibly get into the body of donors.

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What are the particles made of?

Some studies show that some or all of the particles can consist of dried blood or proteins, i.e. they can be at least partially organic. In contrast, other studies show that particles can also be formed that have the same chemical composition as the hinge of the centrifuge inserts, which means that they can become detached from it.

This swivel joint is made up of two parts: one part is ceramic and consists of metal compounds, especially aluminum oxide. The other part of the swivel joint is made of hardened plastic based on phenolic resin. Among other things, formaldehyde and polycyclic aromatic hydrocarbons are used for its production. The latter are considered carcinogenic. It is unclear whether remnants of this can be contained in the swivel joint. However, the studies carried out often only examined individual cases, not systematically a large number of plasma products. Haemonetics said when asked that the company had tested the substances extensively to ensure that they were "safe and non-toxic" for people.

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Does this affect all devices or only some?

According to internal documents, centrifuge inserts that are operated in two different types of machines from Haemonetics are affected. One is the plasmapheresis machine PCS2. According to internal data from Haemonetics, more than 1,600 PCS-2 systems were in use in Germany in 2018. Incidents with particles are also documented for another Haemonetics machine: the MCS +. This device can not only collect plasma, but also platelets. It works on the same principle. How many particle incidents can be assigned to the PCS2 and how many to the MCS + machine is not clear from the documents. According to the data, the problem occurs with different batches of centrifuge use.

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What does the manufacturer say about the allegations?

Upon request by ZEIT, Haemonetics has stated that its machines are safe. Haemonetics calls the fact that humans could have been endangered by detached particles as "wrong and unfounded". According to the company, a total of around 360 million plasma has been donated worldwide since 2005 with the company's machines. Particles were reported to the company in 0.0006 percent of all donations. These include cases in which particles were found in the plastic material before the donation, so that it was never used. Haemonetics does not tell how many cases there have been. The plasma collection sets have no harmful effects on people, the company said. A health risk for patients or donors is not to be feared.

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What do doctors say about it?

Transfusion doctors with whom ZEIT spoke reacted in surprise to possible problems with particles. Rainer Blasczyk, head of the Institute for Transfusion Medicine and Transplant Engineering at the Hannover Medical School, said that he had never heard of detached particles when donating plasma and did not suspect that something like this could happen. Haemonetics is a renowned company and actually known for quality. Blasczyk says there should be no detachment of particles from the apheresis machines. And: "Nothing should get out of the machine into the human body." If the allegations are correct, he sees a "potential danger for donors".

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What risk could the particles pose?

It is currently unclear. To date, there is no known case in which a disease can undoubtedly be attributed to a Haemonetics machine. A French expert committee came to the conclusion in 2017 that without further studies and information from Haemonetics, no statement could be made about the risk for plasma donors. Dirk Walter also confirms this. The chemist and human biologist at the University Hospital in Gießen is concerned with the effects of substances on the human organism. In principle, small and tiny particles that get into the blood could have different effects in the body, he says.

If they collect on the inner wall of blood vessels, they can narrow them. The immune response that the organism triggers against the foreign bodies can lead to inflammation in the long run. And if toxic substances are released from the particles, this could damage the genetic makeup of cells and possibly have a carcinogenic effect. However, Walter considers the particles, which according to the available studies can be rubbed off the rotary joints, rather bio-resistant, i.e. not soluble in the body. It cannot be ruled out that residues of formaldehyde or polycyclic aromatic hydrocarbons could come into contact with blood. When asked about the risks, Haemonetics points out that according to some statements by French authorities, there is no proven risk for donors or patients.

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Do long-term donors have to worry?

"The decisive factor is the concentration and the time for which the exposure takes place," says particle expert Walter. Under no circumstances should everyone who has donated plasma in the past have to worry about getting cancer, for example. "The organism has mechanisms that can repair possible defects." Only when these are overwhelmed by a permanent exposure to pollutants can it become a concern. The internal documents from international research suggest that incidents with particles rarely occur. However, it is not known in how many cases microparticles have formed that were not noticed and could have been transferred to donors. "It is unsatisfactory that you do not know all of this," says Walter. So you can neither acquit the company nor reassure donors and patients. The facts should now be examined thoroughly.

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Are the devices being withdrawn from circulation?

So far, the operation of the PCS2 machines has only been stopped in France. In 2018, the French medical device authority made it impossible to use the machine by prohibiting operation with the only disposable set approved in France. The PCS2 and the related MCS + are currently still in use in Germany. The most recent German particle case in the internal documents comes from last year.

Transfusion doctors such as Peter Hellstern and Rainer Blasczyk demand that the incidents should be addressed by the German authorities. To the competent authority, the Federal Institute for Drugs and Medical Devices (BfArM), only three particle cases have been reported since 2005. The remaining centers with particle cases reported them only to the company Haemonetics, according to the data available to ZEIT. The BfArM states that it is desirable that all incidents are reported to the authority. But the office cannot force this.

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What should plasma donors do that fear consequential damage?

The doctor Blasczyk advises to keep the possibility of contamination at least in the back of the head. If a disease arises, one could consider having an expert check carried out to determine whether it could have anything to do with the particles. "But it will be very difficult to prove that." An increased inflammatory activity in the body, for example, can have many causes. "There will be few ways to hold the company liable for something that will happen to donors in the future," says Blasczyk. However, one could follow how possible lawsuits against the company turn out - for example the lawsuit that was initiated by two former Haemonetics employees in France. "Ultimately, I would also expect the company to speak to the donors."

Read the detailed report on blood plasma research here.

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