Green Plasma Mystery Excerpt

Here’s an excerpt from Chapter 9 in my book, In the Name of The Pill. I’m hoping that it can spark a conversation not only about hormonal birth control, but also about copper IUDs, TRALI, the motives of the medical industry, and why we aren’t more concerned about copper’s affect on women:

Green Plasma Mystery

A group of doctors turned detectives may have tackled a case that best demonstrates how little things have changed since those early days of The Pill. It was 2008, well after the current generation of hormonal birth control had been introduced.

While in surgery at the University of Pennsylvania, the doctors were taken aback when a unit of plasma “with a striking green color entered their operating room.” Plasma is normally straw yellow. So the vivid green appearance troubled them. Although the blood bank assured them the plasma was safe, the anesthesiologist refused the unit and sent it back for disposal.

The team shared photos of the plasma unit with thirty other members of their department who responded with similar bewilderment. They began to investigate this mysterious green phenomenon and reported their findings in the journal, Anesthesiology:

“We could find no reports on green plasma in the past 40 years in either the surgical or the anesthesia literature, which perhaps explains the lack of knowledge on the part of today’s clinicians. However, we found several articles dating back to the 1960s.”

Photo credit: Pranidchakan Boonrom

What they found in the studies from decades prior was that researchers had begun to see a wave of green plasma donations coming from young women shortly after the introduction of The Pill. The source of the color was actually a blue precipitate later identified as the copper-carrying protein, ceruloplasmin. The bright green hue resulted from the mixture of plasma’s normal yellow color with an overabundance of the blue protein.

In one of the old studies, researchers noted that estrogen increases copper retention and, consequently, elevates ceruloplasmin levels. So, for their research, they identified fifteen donors who had elevated ceruloplasmin levels and checked their histories. Sure enough, all of them were taking oral contraceptives, and all of them had green plasma.

The current-day doctors at Penn must have been perplexed. Decades earlier, doctors had identified the source of the green color, linked it to oral contraceptives, and then… they just dropped it.

Lots of Loose Ends

While studies related to green plasma may have come to a sudden stop, the effect of synthetic estrogen on copper levels in young birth control patients didn’t. In recent years, there has been a lot of discussion about the impact of copper overload or copper toxicity. As a result, scientists have concentrated more on the biological roles of copper and ceruloplasmin.

While it exists as the primary transport vehicle for copper throughout the body, the main function of ceruloplasmin appears to be iron oxidation. However, depending on its surroundings, it can serve as an oxidant or an antioxidant. This means it can take on very different roles depending on where it is in the body and what stew of lipids and proteins surround it.

Subsequent research has demonstrated correlations between copper/ceruloplasmin levels and a whole host of maladies that have also been linked to hormonal birth control. You will read about many of these in Part Two. They include anxiety, depression, infertility, hair loss, headaches, diabetes, high and low blood pressure, and breast cancer. Clinical trials have even demonstrated that therapeutic copper depletion can help stop the spread of breast cancer.

Other studies have shown ceruloplasmin levels to be an effective biomarker for thyroid disease and cancer, as well as heart failure. There seems to be an almost endless parallel between the effects of copper overload and the known side effects of birth control, which isn’t surprising since we know an increase in estrogens spawns greater copper retention.

Further studies have also demonstrated that high copper levels can be passed through the placenta. In fact, elevated copper levels in newborns are quite common today. This is significant because high copper levels at birth have been linked to autism, ADHD, and even endometriosis.

Clearly, ceruloplasmin drew the attention of many curious investigators across the medical spectrum over the years. A multitude of published studies have explored the correlation between ceruloplasmin and all these ill effects on the human body, yet the doctors at Penn couldn’t find a single piece of literature since 1969 tying it back to birth control or the young women with green plasma.

Hidden Threats to Non-Users

In medical research, it’s relatively common to have more questions than answers. However, when hormonal contraceptives are involved, the question-to-answer ratio becomes absurd. It’s as if those who control the funding don’t want to find many of the answers.

If the final two questions in her letter to Sen. Nelson are any indication, Barbara Seaman must have had the same suspicion. This was her last question, “Why have important investigators found their funds cut off?” I doubt it was coincidental that the preceding question went like this:

 “What hidden threats to the health of non-users are contained in the pill? I am enclosing [clippings] about the green-tinted blood plasma in pill users. Nobody knows what this means, and yet Stanford has apparently decided to go ahead and use such plasma for transfusions anyway.”

Incidentally, Ms. Seaman’s letter was penned in 1969, the same year as the final ‘green plasma’ study.

But, halting green plasma studies doesn’t make green plasma go away. If it was so common among birth control users, how come so few doctors today have ever seen it? The simple answer is that blood banks did ultimately decide to remove green plasma from their supplies. The American Red Cross came up with visual guidelines for blood components that have been adopted by several other blood services and blood banks around the world.

Ironically, at least one team of modern-day researchers suggests green plasma should “be actively re-introduced into the medical community for transfusion of critically injured and bleeding patients.” They argue that, in cases where the patient experiences life-threatening bleeding, green plasma is perfect because of its “superior hemostatic properties” – in other words, its tremendous ability to clot.

If this were an audiobook, this is where I would insert a loud record scratch followed by a dramatic pause to make sure the listener knows we just went off the rails.

Imagine this. Researchers compared green plasma with normal yellow plasma and discovered that the green-tinted samples had higher hypercoagulation values (clotting ability) across the board. Given this knowledge, you might think they would recommend that women with green plasma should be warned about the possibility of clotting disorders, or at the very least, that more tests should be done to see if women with green plasma experience more blood clots. Instead, they saw it as an opportunity to use the Super-Clotting plasma as a resource in the operating room.

Rejecting Women’s Plasma

Unfortunately, this callous attitude toward women’s health seems to be a continuation of the norm from the early days of The Pill. Indeed, the case of the green plasma mystery offers more damning evidence to affirm Betsy Hartmann’s statement that “family planning has been divorced from the concern for women’s health and well-being.”

While there was much concern about green plasma because of its appearance, something bigger was happening in the realm of the unseen, and it may not be limited to those with green plasma.

Plasma is one of the components derived from donated blood after it has been separated, and a disturbing number of patients were having severe reactions to their plasma transfusions. In 1992, doctors documented the first known fatality related to what is now known as transfusion-related acute lung injury (TRALI). In most cases, their blood pressure would drop, they developed shortness of breath, and their lungs began to fill with fluid. TRALI is essentially an immune response – the recipient’s body defending itself against something contained in the donor’s blood.

To this day, doctors understand very little about the exact causes of TRALI, but one of the things they were able to confirm early on was that the problem seemed to be tied to female donors. The industry needed to take action as the number of TRALI cases began to climb. It would soon become the leading cause of transfusion-related death.

In 2003, the United Kingdom led the response by implementing a male-predominant policy for plasma donations. The blood-banking industry in the United States followed their lead, and by 2007, recommended that no plasma from female donors be used in transfusions. That’s right – for over a decade, the blood-banking industry has avoided using women’s plasma for transfusions. When this decision was made, they didn’t want a lot of publicity because they were afraid women would stop donating blood altogether.

Their primary hypothesis at the time was that the lung injuries had to do with antibodies contained within the blood of the female donors. Antibodies are proteins produced by the immune system to fight off unrecognized threats such as viruses or bacteria, but researchers pointed out that a woman’s body can also create antibodies in reaction to the presence of the father’s cells when she becomes pregnant.

The media picked up this convenient storyline and ran with it. At least one major headline proclaimed, “Blood transfusions from women who have been pregnant could kill men.” However, it wasn’t just men being killed by TRALI, nor were results conclusive that pregnancy-related antibodies were the sole offenders.

We’ve Got Our Answer

Let’s look at another way, specific to women, that antibodies are developed. As far back as 1969, studies revealed that many women on The Pill experienced increased serum levels of certain antibodies. One trial, which focused on the autoimmune disease, lupus, tested women who developed rheumatic symptoms after starting The Pill and found that serum antinuclear antibodies (ANA) were present in a vast majority of these young women.  For most of the patients, the abnormalities disappeared when they stopped taking birth control. Today, the ANA blood test is a primary tool used by physicians to assess whether a patient may have systemic lupus erythematosus (SLE).

Antibodies are not unique to lupus. In fact, ‘direct evidence of disease-causing antibodies’ is the first criterion for a disease to be classified as autoimmune. Anytime the immune system is activated, antibodies will be involved. Consequently, elevated levels of particular antibodies accompany every autoimmune disease.

So, here’s where we are in the story arc:

1)  Autoimmune Disease is a classification of disease in which nearly 80 percent of all diagnoses are women.

2) TRALI is a severe alloimmune response in transfusion patients, which seems most likely to occur when the donor is a woman. (‘Auto’ means ‘self’ so autoimmune is an immune response to antigens from one’s self. And, ‘allo’ means ‘other’ so this is a response to antigens from outside one’s self.)

3) Aside from TRALI, blood banks already had a policy of discarding many plasma donations from young women on birth control because of its unusual appearance, knowing the green hue is caused by a metabolic effect on serum proteins.

4) Hormonal birth control use has been shown to increase the risk of several common autoimmune diseases.

When you add these facts together, you would expect some curious investigator might be eager to see what the correlation is between TRALI-related donors and contraceptive use, yet not a single study exists. To be fair, blood banks exclude people with autoimmune diseases from donating. So, most researchers may assume that risk has already been eliminated. However, several studies, including the lupus study previously mentioned, have shown that these elevated antibody levels can flourish in women on hormonal contraceptives even when they don’t display any symptoms and/or before they’ve been diagnosed with an autoimmune disease.

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