Transgender adult reference intervals taking shape

Since the patient was listed in the EMR as male, the transfusion service laboratory immediately prepared a shipment of uncrossmatched type O, RhD-positive packed RBCs. This was problematic because “in general, when people are of childbearing ages and have a uterus and ovaries, we like to transfuse them with O-negative blood because they won’t have the alloreactivity if they have an Rh-positive fetus,” she said. A literature search on the subject of transgender transfusion produced “basically nothing.”

Sex considerations for transfusion medicine are fairly simple, she noted. “For recipients, it’s basically the type of blood, such as giving O-negative to people who may want to impregnate themselves. For the donor, it’s HLA alloantibodies; if you are an ICU patient, we prefer to transfuse blood of someone who has never been pregnant before because that can lead to adverse downstream effects.”

That sexual orientation is used as a risk prevention strategy in transfusion medicine creates donor barriers. “They don’t ask, ‘Have you been pregnant before?’ They look and say, ‘You’re female’ and then might ask if you’ve been pregnant. But if they perceive your gender or sex as male, they probably won’t ask. So you run the risk of giving the wrong blood to someone.”

In the case of the 40-year-old transgender male, the UW laboratory noticed that the order was placed from a gynecology floor for a male patient and called for clarification. The patient was transfused with the correct blood product: O, Rh-negative units. “Calling for clarification is not something we usually want,” she said. “If we had better EMR receptivity in the LIS, that could be avoided.”

Increased risk of thrombosis is an issue that comes up in patients on hormone therapy, but “it’s not as bad as one would think,” Dr. Greene said. Transgender women in particular are at increased risk of thrombosis, but the incidence is low. “The reason is estrogen causes procoagulant shifts,” she said. “Usually when you have very high concentrations of estrogen, you’re about to have a baby. There is a lot of blood so we want to be able to clot. One of the functions of estrogen is it has these procoagulant shifts that increase hemostatic factors and decrease antithrombotic factors.”

Study models with oral contraceptives or postmenopausal women on hormone replacement therapy are not equivalent to transgender women, she said.

In transgender men, testosterone stimulates erythrocytosis and erythropoiesis but has not been shown to increase the rates of venous thromboembolism.

“We wanted to answer the question of how bad the clotting risk is for transgender women and did a systematic review to assess VTE risk,” she said. A literature search of hundreds of studies left them with 12 that had data on outcomes of estrogen use in transgender women. “The end game was that, yes, transgender women do have a slightly increased risk of clotting, but it is basically about the same risk as someone who would be taking oral contraceptives.” Some variables, such as smoking or oral versus injected therapy, were not part of the 12 studies they reviewed. “But I like this study,” she said of the systematic review, “because it showed that one of the things we think to be the least safe is actually not as big of a deal.” Dr. Greene said more studies about clotting risk in transgender women are to come.

A recent survey of LIS companies provided insight into their ability to capture, retain, and display transgender patient information. Martha E. Lyon, PhD, DABCC, a clinical biochemist in the Department of Pathology and Laboratory Medicine, Royal University Hospital, Saskatchewan Health Authority, Saskatoon, speaking in the same AACC session, said she heard Dr. Greene speak a few years ago at a Canadian clinical chemistry meeting. “I realized I had a whole lot more I needed to learn about transgender patients and how we can provide a better service to them.”

She focused on laboratory information systems and their readiness to represent transgender patients. Dr. Lyon and her colleagues consulted a 2018 CAP TODAY article on LIS companies’ views of their customers’ needs and the accompanying LIS product guide.

“We took the contact information for the 30 companies and put together a very small survey,” Dr. Lyon said. Seven LIS companies responded quickly to the first survey email request she sent on April 22, and three more companies answered her follow-up request on May 22. All companies were informed that responses would be presented as pooled and anonymized data in the AACC annual meeting session.

“The first question we asked was, ‘Does your LIS/EMR product collect, retain, and display patient biological sex?’” That information can cue Pap tests and prostate exams, Dr. Lyon said, and it can be used for linking the laboratory test results or reference ranges. Seven companies said they collect patient biological sex information; one company said it did not.

(Two companies that didn’t respond to specific questions and instead gave a general response, Dr. Lyon said, are listed as not answering questions in the survey results.)

“We wanted to ask a little bit more about the information collected with respect to biological sex,” Dr. Lyon said, “and so we said, ‘If you collect [patient biological sex], is it male/female, male/female or other/unknown, or is it flexible? Can it be designed and customized for your clients?’”

“We found that the companies that responded were able to answer more than one of these,” she said. One company only had the option of a male/female category, six companies had male/female or other/unknown categories, and four companies also had an option for a flexible/customized-by-client category. “It was a combination for several of the companies.”

The next question asked whether companies collected, retained, and displayed patient gender information separately from patient sex information. Seven LIS companies said yes; one company said no.

“We went further and asked, ‘If you have the data field for assigned sex at birth, do you actually capture that information?’ Seven LIS companies said yes, and one company said no.”

For gender identity, three companies said they were capable of capturing this information, and five said they were not. “It will depend on the information being captured,” Dr. Lyon said. “Is it male to female? Is it gender choosing not to disclose? We never went into that level of depth with respect to the questionnaire.”

Dr. Lyon also asked about the ability to capture preferred patient name and pronouns. “We know that the gender identity field in the electronic health record is very important for clinical care, but we also know the importance, especially for frontline staff, to be able to appropriately address the patients. When we avoid misgendering the patients, it’s better care and more confidence-building for all individuals involved.”

A follow-up question asked how long it would take companies to add the ability to capture information on assigned sex at birth and gender identity. Five companies said they thought they would be ready in one to two years, while three companies were already able to capture that information.

Five companies said they planned to offer reference range fields for transgender patients. Three said they did not.

“We then asked, ‘Are your customers requesting the capability of capturing more fields for transgender patients?’” Dr. Lyon said. Two companies said yes and six said no, and that result surprised Dr. Lyon. “What this indicates is the need to promote more awareness of why it is important to be able to capture this information and to provide better service to our transgender patients. It’s very important within the laboratory medicine area.”

Several companies submitted comments about the future development or barriers in LIS/EMR systems as they relate to transgender patient representation. They found a major theme and a predictable one, Dr. Lyon said: reference ranges.

One company wrote that barriers include “the lack of industry standards and even the lack of industry consensus as to how transgendered patient reference ranges should be managed . . . . There are not enough studies to create the patient populations to determine reference range standards.”

Another company wrote, “For the laboratory to assume the responsibility for the interpretation of reference ranges based on birth sex with or without hormone therapy and with or without surgical procedures for a transgendered person may not be appropriate.”

One company commented on the need for more research “to determine the appropriate reference ranges for transgender and gender-nonconforming populations. The effects of hormone replacement therapy and other medical interventions on target reference ranges is not well understood and preliminary research has yet to provide clear results.”

Amy Carpenter Aquino is CAP TODAY senior editor.