Science & Research

Blood work

Just a wee drop of the red stuff can reveal a lot about your health

Diane Jaslowski, a laboratory technologist at CancerCare Manitoba, prepares blood samples for a complete blood count test.
Diane Jaslowski, a laboratory technologist at CancerCare Manitoba, prepares blood samples for a complete blood count test.
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What your blood says about your health

BY JOEL SCHLESINGER
Winnipeg Health Region
Wave, March / April 2015

Dr. Ryan Zarychanski slides a blood smear fixed to a thin wafer of glass under the barrel of his microscope and peers through the lens.

The sample belongs to a patient who has been experiencing a host of unexplained and potentially serious symptoms, including spiking fevers, weight loss and weakness.

As a hematologist at CancerCare Manitoba, Zarychanski's job is to analyze the blood for clues as to what might be causing the patient's health issues.

And, in this case, it doesn't take him long to pinpoint a problem. As he studies the sample before him, Zarychanski notes increased white blood cells that are cause for concern.

High numbers of white blood cells generally suggest the presence of an infection, but depending on size and features, they can also be evidence of cancer.

In order to arrive at a definitive answer, Zarychanski orders up a round of more sophisticated blood tests, including one called a real time quantitative polymerase chain reaction (PCR) test. It uses state-ofthe- art technology involving incredibly precise chemical processes to analyze a person's DNA in the blood.

To perform a PCR test, about a teaspoon of blood is collected from the patient. DNA from the patient's white blood cells is then extracted by a laboratory technologist. Small tubes of purified DNA, along with a mix of ingredients to make DNA, are then placed in a thermocycler, a piece of equipment that amplifies small quantities of DNA into millions of copies to allow analysis. The thermocycler looks a little like a printer/fax machine, but instead of printing paper, it makes copies of your genetic code - either normal, or maybe a code that has caused cancer.

In this particular case, the test reveals a specific DNA mutation that causes chronic myelogenous leukemia - or CML, for short.

While confirmation of cancer is never great news, the discovery in this case actually offers a reason for optimism. Advances in blood testing technology that allow hematologists to diagnose various forms of cancer or other diseases have also made it possible to come up with highly effective treatments and even cures in selected cancers.

Chronic myelogenous leukemia (CML) is a case in point. Not long ago, this form of leukemia would have been treated with highly toxic chemotherapy followed by a bone marrow transplant. Even then, the survival rate was not great. But thanks to advances in blood testing that allowed the medical community to pinpoint the genetics of this particular disease, researchers have been able to develop a drug that targets the cancer's genetic makeup and effectively treats the cancer in over 95 per cent of patients.

The ability to identify and treat a disease like CML underscores the important role blood tests play in the delivery of health care, one that can be traced back hundreds, if not thousands, of years. It also points to the promise of the future, one where blood tests will play an increasingly important role in not only diagnosing diseases, but treating them.

"Blood testing of one kind or another has been around for a very long time," says Zarychanski, who is also an assistant professor in the Department of Internal Medicine at the University of Manitoba.

For centuries, scientists and doctors wondered about what knowledge could be gleaned from studying blood. From ancient Greeks to Islamic scholars to Italian Renaissance men, they have been fascinated by its mysteries: what was blood's purpose, its potential? How can changes in the blood cause or be a sign of a particular disease?

Over time, scientists have uncovered one secret after another - how our circulatory system works, how it feeds every cell in the body with oxygen and leads the fight against infection. Yet each new discovery frequently leads to more questions. And today that's arguably the case more than ever before.

Great leaps in technology over the last 100 years that have allowed scientists to examine the molecular structure of blood have opened a gateway to greater knowledge of disease.

While a doctor may still start an examination by looking at someone's tongue or listening to their heart and lungs, how exactly they examine their blood has changed considerably over time. In times gone by, a blood test would involve examining a sample held up to the light or bled into a bowl, and more recently under the microscope. Comparisons would be made to samples from other patients - either healthy or those with a specific illness.

"As recently as 50 years ago, doctors would assess if someone is anemic by measuring the different layers that the blood sample separates into: red cells at the bottom, white blood cells and then plasma at the top," Zarychanski says.

Over the decades, however, testing has come a long way.

Scientists can now use a machine (called a flow cytometer) that uses light and lasers to count and size cells, bacteria and even viruses in the blood. Leveraging computer technology, physicians and technologists can accurately test for all sorts of things, such as electrolytes (e.g., potassium, calcium), proteins, and genetic material (i.e., DNA). These tests can, for example, reveal how a patient's kidneys or liver is functioning, or whether a person or family is at risk for certain cancers.

At CancerCare and the adjoining Health Sciences Centre Winnipeg (HSC), the blood labs use technology that employs cutting-edge scientific methods to identify and test cells, including cancerous ones.

"One of the largest machines at the main blood lab in HSC can run more than 100 different tests, and then produce an analysis that is digitized and available to physicians across the province," Zarychanski says.

To understand the value of blood tests in our health-care system, says Zarychanski, it helps to think of them separated into the following categories: diagnostic, disease-monitoring, and leading-edge innovations that may one day be routine.

Diagnostic blood tests include the routine kind ordered by your family doctor to check your blood sugar and cholesterol. These might be screening tests aimed at catching potential trouble before a patient develops a serious illness, like heart disease or diabetes.

Whether you are tested or not might depend on your age and risk factors, such as lifestyle and family history. For example, a doctor wouldn't likely test the blood sugar of a 20-year-old patient who isn't experiencing symptoms of diabetes. Instead, a doctor is likely to request a blood glucose test for a 20-year-old male if he has suggestive symptoms, such as constant thirst, frequent urination and blurred vision.

Blood tests can also be helpful in monitoring a patient's condition. They are used, for example, to determine whether treatments for certain cancers have been effective, as well as keeping an eye on its possible side-effects, such as anemia or low white blood cell counts (a common complication of chemotherapy). A doctor might also use blood tests to monitor the levels of anti-seizure medications or some blood thinners to ensure they work properly without toxicity.

But Zarychanski is quick to point out that despite the ability to detect molecules in the blood that can be associated with disease, blood tests cannot be used to detect all diseases, such as the majority of cancers and other serious illnesses. Imaging and biopsy of diseased tissue in addition to other selectively employed tests will always be necessary.

"There are routine tests most of us will get at some point to screen for potential health problems before they cause symptoms, and then there are more specific tests your doctor will request to help diagnose the disease and monitor your response to treatment," he says.

"Right now, for cancers other than those dealing specifically with the blood, like leukemia, the final diagnosis is made based on a biopsy of the tissue. While that could change as we understand more about circulating tumour cells and the blood's role in disease, we're not there yet," he says.

Yet the future for blood testing holds tremendous promise, and not just in regard to diagnosing disease earlier and more accurately.

As Zarychanski explains, the story of blood testing is one of learning about what makes diseases tick.

"We used to look at layers of blood in a tube, and then actual cells under a microscope. Now we are looking within individual cells and the DNA within those individual cells to really get at the nittygritty of what is inside," he says.

Technological innovation that allows doctors to use a blood test to examine patients' DNA will eventually reveal indepth information about their genetic makeup and how a specific individual will benefit from a given treatment.

"This is the leading edge of medicine - and part of what we refer to as 'personalized medicine,'" he says. "The future of medicine is to look at people's genetics and perhaps even the genetics of their tumour, and then select or engineer the right drug in the right dose for the right disorder."

And a blood test, in large part because it's among the least invasive of all tests, will play an increased role in this new world of medicine.

"Consider it a fingerprint - or, perhaps more accurately, a blood-print - of pathology. Because no one's blood is exactly alike, it's a wellspring of individual genetic information," he says.

Although many of the advances necessary to tailor-make treatments are still years away, the medical community already recognizes that the one-size-fitsall prescription to treat illness is largely outdated.

"It's sort of like this: Do you think an 18-year-old and his 80-year-old grandmother would have the same ability to metabolize and tolerate medications? Would the biology of their cancers necessarily be similar? Of course not. Yet if you have a headache and need Tylenol, the 18-year-old boy's dose would be the same as the 80-year-old adult's dose, and if you have lymphoma, each patient would receive the same drugs in the same doses," he says. "We have remarkably similar treatments for adults that do not consider a person's unique characteristics - and this is likely far from ideal when one considers genetic differences and the ability to metabolize medications."

Perhaps the greatest promise of personalized medicine is in the treatment of cancer.

As Zarychanski explains, cancer's calling card is uncontrolled cell replication, usually sparked by a genetic mutation - either inherited or the result of DNA damage from exposure to chemicals, viruses or other environmental factors. Moreover, he says, because cancer ultimately uses our DNA and cellular machinery against us to endlessly divide, creating new malignant cells, even cancers with similar biology differ from one another.

"One patient's lung cancer may be similar to another's, and may require similar treatment, but another patient's lung cancer may be genetically unique and not respond to the very same drug, says Zarychanski. "In fact, all patients have a unique genetic blueprint that influences how their bodies and cancers will respond to chemotherapy and other treatments. With this information in hand, one day, doctors may be able to select treatments with these differences in mind."

CML, for example, is one of a handful of cancers that can now be quickly and accurately diagnosed and treated, thanks to advances in blood testing over the last 15 years. "CML is the quintessential example," says Zarychanski. "It's where we are headed. Many of the new therapies in evolution are targeting specific aspects of a certain cancer for which we could offer a therapy that works."

Among the new treatments being developed are those that use genetically engineered viruses to target a unique mutation specific to a type of cancer. Using a malignant cell's own DNA to replicate, the virus invades the cell and multiplies to the point where it ultimately destroys the cancerous cell while leaving healthy cells unharmed. Yet most tests that search for cancer's genetic markers in the blood are experimental and have yet to be used successfully in a clinical setting.

Even with the anticipated advances, blood tests will likely always be a doubleedged sword when it comes to diagnosing and determining proper treatment, says Zarychanski.

And he should know. In addition to being a respected hematologist and scientist, Zarychanski is also Director of the Knowledge Synthesis platform at the George and Fay Yee Centre for Healthcare Innovation, a role that involves evaluating the latest medical research, including, but not limited to, the efficacy of blood tests. To his expert eyes, a blood test is a powerful tool, but it must be used cautiously. "There are always two sides to the coin when it comes to all our advances with blood tests," he says.

Except in instances of screening, patients usually present symptoms first before a blood test can be used effectively - essentially confirming a physician's suspicion.

An example of the potential problems that can arise is the tale of the prostate specific antigen blood test (PSA). In the past, PSA testing was recommended and routinely performed to detect prostate cancer. "The belief was that if we could detect prostate cancer earlier, deaths could be reduced," says Zarychanski.

"Doctors embraced the testing and men over the age of 50 lined up to have their PSA measured. But then several randomized controlled trials (the type of trials that produce the highest quality of evidence to inform decision-making) were performed that concluded PSA has minimal to no ability to reduce mortality from prostate cancer, and that the benefits of routine screening are likely outweighed by the potential harms to quality of life."

In other words, screening results in an increase of unnecessary and invasive biopsies that lead to overdiagnosis of low-grade cancers that are not otherwise likely to progress to symptomatic disease.

In many cases, these men are offered treatments, such as surgery or radiation therapy. While biopsies are associated with pain, anxiety, discomfort and risk of infection, common complications of surgery include incontinence and impotence.

"So at end of this medical adventure, this blood test must be good, right? asks Zarychanski rhetorically. "Not in the majority of men," he says.

"So the recommendation now, a recommendation based on high-quality evidence instead of our collective wish to do good, is not to routinely screen for PSA," he says. "Instead, the test is best reserved to investigate concerning symptoms and only after patients fully understand the risks and benefits of PSA screening." A discussion with your doctor is required prior to testing.

(It is important, says Zarychanski, to distinguish between the PSA test and other screening programs offered through CancerCare Manitoba for breast, colon and cervical cancer. These programs are supported by the results of medical trials that, on the whole, confirm reduced mortality or morbidity from cancer.)

The lesson, of course, is that while blood testing is an incredibly valuable tool, it is not a diagnostic panacea. "It would be foolish to put all of our eggs in one diagnostic basket," Zarychanski says. "We've enjoyed great advances but risks and benefits must always be weighed. No test is without risk, and no therapy is without side-effects."

Another questionable example of the misuse of a blood test involves inherited causes of blood clots. While this type of testing was common in the past, and is still frequently requested, knowledge of inheritable disorders rarely, if ever, impacts treatment decisions. "And even if the information does influence decisions your doctor makes, we generally have no real idea if these decisions are associated with more good than harm," says Zarychanski. "A willingness for your physician to 'do good' is an insufficient premise to justify costly therapies associated with potential side-effects. While data does not exist to justify many decisions, we must be vigilant to incorporate existing knowledge."

Moreover, knowledge about a genetic condition that will not impact treatment may render a patient ineligible for life and travel health insurance given the riskaverse nature of insurance companies.

"Physicians must consider the adverse implications of testing and communicate these risks to their patients," he says.

As technology advances along with our understanding of what blood can reveal about our health, blood tests will continue to play an important role. But they are unlikely to ever be the only tool we use to diagnose disease, says Zarychanski. "Health and illness are just too complex for one tool of measure, even though one little drop of blood is itself a fountain of knowledge for those who study it."

Joel Schlesinger is a Winnipeg writer.

Wave: March / April 2015

About Wave

Wave is published six times a year by the Winnipeg Health Region in cooperation with the Winnipeg Free Press. It is available at newsstands, hospitals and clinics throughout Winnipeg, as well as McNally Robinson Books.

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