Today, we take a brief look at how researchers in Ontario (Canada) are opening the door to using a simple blood test to help determine the cancer risk for an individual.

Platelets 101

What are platelets? Marlene Williams, M.D., director of the Coronary Care Unit at Johns Hopkins Bayview Medical Center, offers this excellent explanation:

“Platelets are the cells that circulate within our blood and bind together when they recognize damaged blood vessels.”

She continues: “When you get a cut, for example, the platelets bind to the site of the damaged vessel, thereby causing a blood clot. There’s an evolutionary reason why they’re there. It’s to stop us from bleeding.”

When I think about the relationship between cancer and platelets, it is usually in the context of anti-cancer treatment. For example, low platelet counts (thrombo-cytopenia — THROM-bo-sigh-toe-PEE-ne-ah) can result from chemotherapy damaging the bone marrow reducing platelet production. Such injury is usually temporary.

Lymphoma and the blood cancer known as leukemia can invade the bone marrow. When the cancer cells occupy significant volumes of the marrow, an individual can have challenges making the platelets that they need.

Types of thrombocytopenia (low platelet count)

The Cleveland Clinic (USA) explains that there are three main classes of thrombocytopenia, including:

• Platelet destruction (such as an auto-antibody attached to the platelet surface).
• Platelet sequestration (isolation), for example, in an enlarged liver or spleen.
• Decreased platelet production associated with certain bone marrow diseases.

Platelets and cancer

Researchers analyzed data from nearly nine million Ontario residents to better understand the relationship between platelet levels and cancer risk. The subjects were enrolled in the provincial health insurance plan and had a routine complete blood count test between 2007 and 2017.

The Canadian researchers matched each patient with cancer to three controls (individuals without a cancer diagnosis) according to age, sex, and healthcare use patterns.

The scientists then calculated the cancer risk associated with each category of platelet counts at intervals up to ten years after a blood test.

Here are the odds ratios for those very high platelet counts. For example, an odds ratio of 4.6 means that those with very high platelet levels had a 4.6-times higher risk of getting ovarian cancer.

Study author Giannakeas observes that “the differences in our findings by cancer type surprised me.” He adds, “Clearly, there is a mechanism on platelets occurring with certain cancer types but not with others, such as breast and prostate cancer.”

The increase in relative risk appeared most pronounced for ovarian, lung, kidney, and gastrointestinal cancers (including esophagus, stomach, colorectal, and other gastrointestinal cancers).

Platelets and cancer — My take

Is the elevation in platelets a marker for future cancer, or does it indicate the presence of a current malignancy? The increase in risk appeared most significant in the six months after diagnosing thrombocytosis (too many platelets) and decreased rapidly after that.

These findings suggest that increased platelets may be a marker for the presence of existing cancer, rather than a factor associated with increased cancer risk. Cancer may be causing the platelet increase. If the platelet increase were a marker for future cancer, instead of being associated with current cancer, the risk period would likely be longer than six months.

An elevated platelet count may someday serve (along with other screen tools) as a marker for the presence of some cancer type. Thank you for joining me today. Nothing actionable, but the results hint at a future approach using a simple and relatively inexpensive blood test.

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Without blood, the human body would stop working.

Blood is a specialized body fluid. It has four main components: plasma, red blood cells, white blood cells, and platelets. Blood has many different functions, including:

• transporting oxygen and nutrients to the lungs and tissues
• forming blood clots to prevent excess blood loss
• carrying cells and antibodies that fight infection
• bringing waste products to the kidneys and liver, which filter and clean the blood
• regulating body temperature

The blood that runs through the veins, arteries, and capillaries is known as whole blood, a mixture of about 55 percent plasma and 45 percent blood cells. About 7 to 8 percent of your total body weight is blood. An average-sized man has about 12 pints of blood in his body, and an average-sized woman has about nine pints. 

The Components of Blood and Their Importance

Many people have undergone blood tests or donated blood, but hematology – the study of blood – encompasses much more than this. Doctors who specialize in hematology (hematologists) are leading the many advances being made in the treatment and prevention of blood diseases.

If you or someone you care about is diagnosed with a blood disorder, your primary care physician may refer you to a hematologist for further testing and treatment.

Plasma

The liquid component of blood is called plasma, a mixture of water, sugar, fat, protein, and salts. The main job of the plasma is to transport blood cells throughout your body along with nutrients, waste products, antibodies, clotting proteins, chemical messengers such as hormones, and proteins that help maintain the body’s fluid balance. 

Red Blood Cells (also called erythrocytes or RBCs)

Known for their bright red color, red cells are the most abundant cell in the blood, accounting for about 40 to 45 percent of its volume. The shape of a red blood cell is a biconcave disk with a flattened center – in other words, both faces of the disc have shallow bowl-like indentations (a red blood cell looks like a donut).

Production of red blood cells is controlled by erythropoietin, a hormone produced primarily by the kidneys. Red blood cells start as immature cells in the bone marrow and after approximately seven days of maturation are released into the bloodstream. Unlike many other cells, red blood cells have no nucleus and can easily change shape, helping them fit through the various blood vessels in your body. However, while the lack of a nucleus makes a red blood cell more flexible, it also limits the life of the cell as it travels through the smallest blood vessels, damaging the cell’s membranes and depleting its energy supplies. The red blood cell survives on average only 120 days.

Red cells contain a special protein called hemoglobin, which helps carry oxygen from the lungs to the rest of the body and then returns carbon dioxide from the body to the lungs so it can be exhaled. Blood appears red because of the large number of red blood cells, which get their color from the hemoglobin. The percentage of whole blood volume that is made up of red blood cells is called the hematocrit and is a common measure of red blood cell levels.

White Blood Cells (also called leukocytes)

White blood cells protect the body from infection. They are much fewer in number than red blood cells, accounting for about 1 percent of your blood.

The most common type of white blood cell is the neutrophil, which is the “immediate response” cell and accounts for 55 to 70 percent of the total white blood cell count. Each neutrophil lives less than a day, so your bone marrow must constantly make new neutrophils to maintain protection against infection. Transfusion of neutrophils is generally not effective since they do not remain in the body for very long.

The other major type of white blood cell is a lymphocyte. There are two main populations of these cells. T lymphocytes help regulate the function of other immune cells and directly attack various infected cells and tumors. B lymphocytes make antibodies, which are proteins that specifically target bacteria, viruses, and other foreign materials.

Platelets (also called thrombocytes)

Unlike red and white blood cells, platelets are not actually cells but rather small fragments of cells. Platelets help the blood clotting process (or coagulation) by gathering at the site of an injury, sticking to the lining of the injured blood vessel, and forming a platform on which blood coagulation can occur. This results in the formation of a fibrin clot, which covers the wound and prevents blood from leaking out. Fibrin also forms the initial scaffolding upon which new tissue forms, thus promoting healing.

A higher than normal number of platelets can cause unnecessary clotting, which can lead to strokes and heart attacks; however, thanks to advances made in antiplatelet therapies, there are treatments available to help prevent these potentially fatal events. Conversely, lower than normal counts can lead to extensive bleeding.

Complete Blood Count (CBC)

A complete blood count (CBC) test gives your doctor important information about the types and numbers of cells in your blood, especially the red blood cells and their percentage (hematocrit) or protein content (hemoglobin), white blood cells, and platelets. The results of a CBC may diagnose conditions like anemia, infection, and other disorders. The platelet count and plasma clotting tests (prothombin time, partial thromboplastin time, and thrombin time) may be used to evaluate bleeding and clotting disorders.

Your doctor may also perform a blood smear, which is a way of looking at your blood cells under the microscope. In a normal blood smear, red blood cells will appear as regular, round cells with a pale center. Variations in the size or shape of these cells may suggest a blood disorder.

Where Do Blood Cells Come From?

Blood cells develop from hematopoietic stem cells and are formed in the bone marrow through the highly regulated process of hematopoiesis. Hematopoietic stem cells are capable of transforming into red blood cells, white blood cells, and platelets. These stem cells can be found circulating in the blood and bone marrow in people of all ages, as well as in the umbilical cords of newborn babies. Stem cells from all three sources may be used to treat a variety of diseases, including leukemia, lymphoma, bone marrow failure, and various immune disorders.

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Arteries

Arteries carry blood away from the heart. Pulmonary arteries transport blood that has a low oxygen content from the right ventricle to the lungs. Systemic arteries transport oxygenated blood from the left ventricle to the body tissues. Blood is pumped from the ventricles into large elastic arteries that branch repeatedly into smaller and smaller arteries until the branching results in microscopic arteries called arterioles. The arterioles play a key role in regulating blood flow into the tissue capillaries. About 10 percent of the total blood volume is in the systemic arterial system at any given time.

The wall of an artery consists of three layers. The innermost layer, the tunica intima (also called tunica interna), is simple squamous epithelium surrounded by a connective tissue basement membrane with elastic fibers. The middle layer, the tunica media, is primarily smooth muscle and is usually the thickest layer. It not only provides support for the vessel but also changes vessel diameter to regulate blood flow and blood pressure. The outermost layer, which attaches the vessel to the surrounding tissue, is the tunica externa or tunica adventitia. This layer is connective tissue with varying amounts of elastic and collagenous fibers. The connective tissue in this layer is quite dense where it is adjacent to the tunic media, but it changes to loose connective tissue near the periphery of the vessel.

Capillaries

Capillaries, the smallest and most numerous of the blood vessels, form the connection between the vessels that carry blood away from the heart (arteries) and the vessels that return blood to the heart (veins). The primary function of capillaries is the exchange of materials between the blood and tissue cells.

Capillary distribution varies with the metabolic activity of body tissues. Tissues such as skeletal muscle, liver, and kidney have extensive capillary networks because they are metabolically active and require an abundant supply of oxygen and nutrients. Other tissues, such as connective tissue, have a less abundant supply of capillaries. The epidermis of the skin and the lens and cornea of the eye completely lack a capillary network. About 5 percent of the total blood volume is in the systemic capillaries at any given time. Another 10 percent is in the lungs.

Smooth muscle cells in the arterioles where they branch to form capillaries regulate blood flow from the arterioles into the capillaries.

Veins

Veins carry blood toward the heart. After blood passes through the capillaries, it enters the smallest veins, called venules. From the venules, it flows into progressively larger and larger veins until it reaches the heart. In the pulmonary circuit, the pulmonary veins transport blood from the lungs to the left atrium of the heart. This blood has a high oxygen content because it has just been oxygenated in the lungs. Systemic veins transport blood from the body tissue to the right atrium of the heart. This blood has a reduced oxygen content because the oxygen has been used for metabolic activities in the tissue cells.

The walls of veins have the same three layers as the arteries. Although all the layers are present, there is less smooth muscle and connective tissue. This makes the walls of veins thinner than those of arteries, which is related to the fact that blood in the veins has less pressure than in the arteries. Because the walls of the veins are thinner and less rigid than arteries, veins can hold more blood. Almost 70 percent of the total blood volume is in the veins at any given time. Medium and large veins have venous valves, similar to the semilunar valves associated with the heart, that help keep the blood flowing toward the heart. Venous valves are especially important in the arms and legs, where they prevent the backflow of blood in response to the pull of gravity.

Physiology of Circulation

Roles of Capillaries

In addition to forming the connection between the arteries and veins, capillaries have a vital role in the exchange of gases, nutrients, and metabolic waste products between the blood and the tissue cells. Substances pass through the capillary wall by diffusion, filtration, and osmosis. Oxygen and carbon dioxide move across the capillary wall by diffusion. Fluid movement across a capillary wall is determined by a combination of hydrostatic and osmotic pressure. The net result of the capillary microcirculation created by hydrostatic and osmotic pressure is that substances leave the blood at one end of the capillary and return at the other end.

Blood Flow

Blood flow refers to the movement of blood through the vessels from arteries to the capillaries and then into the veins. Pressure is a measure of the force that the blood exerts against the vessel walls as it moves the blood through the vessels. Like all fluids, blood flows from a high pressure area to a region with lower pressure. Blood flows in the same direction as the decreasing pressure gradient: arteries to capillaries to veins.

The rate, or velocity, of blood flow varies inversely with the total cross-sectional area of the blood vessels. As the total cross-sectional area of the vessels increases, the velocity of flow decreases. Blood flow is slowest in the capillaries, which allows time for exchange of gases and nutrients.

Resistance is a force that opposes the flow of a fluid. In blood vessels, most of the resistance is due to vessel diameter. As vessel diameter decreases, the resistance increases and blood flow decreases.

Very little pressure remains by the time blood leaves the capillaries and enters the venules. Blood flow through the veins is not the direct result of ventricular contraction. Instead, venous return depends on skeletal muscle action, respiratory movements, and constriction of smooth muscle in venous walls.

Pulse and Blood Pressure

Pulse refers to the rhythmic expansion of an artery that is caused by ejection of blood from the ventricle. It can be felt where an artery is close to the surface and rests on something firm.

In common usage, the term blood pressure refers to arterial blood pressure, the pressure in the aorta and its branches. Systolic pressure is due to ventricular contraction. Diastolic pressure occurs during cardiac relaxation. Pulse pressure is the difference between systolic pressure and diastolic pressure. Blood pressure is measured with a sphygmomanometer and is recorded as the systolic pressure over the diastolic pressure. Four major factors interact to affect blood pressure: cardiac output, blood volume, peripheral resistance, and viscosity. When these factors increase, blood pressure also increases.

Arterial blood pressure is maintained within normal ranges by changes in cardiac output and peripheral resistance. Pressure receptors (barareceptors), located in the walls of the large arteries in the thorax and neck, are important for short-term blood pressure regulation.

Circulatory Pathways

The blood vessels of the body are functionally divided into two distinctive circuits: pulmonary circuit and systemic circuit. The pump for the pulmonary circuit, which circulates blood through the lungs, is the right ventricle. The left ventricle is the pump for the systemic circuit, which provides the blood supply for the tissue cells of the body.

Pulmonary Circuit

Pulmonary circulation transports oxygen-poor blood from the right ventricle to the lungs, where blood picks up a new blood supply. Then it returns the oxygen-rich blood to the left atrium.

Systemic Circuit

The systemic circulation provides the functional blood supply to all body tissue. It carries oxygen and nutrients to the cells and picks up carbon dioxide and waste products. Systemic circulation carries oxygenated blood from the left ventricle, through the arteries, to the capillaries in the tissues of the body. From the tissue capillaries, the deoxygenated blood returns through a system of veins to the right atrium of the heart.

The coronary arteries are the only vessels that branch from the ascending aorta. The brachiocephalic, left common carotid, and left subclavian arteries branch from the aortic arch. Blood supply for the brain is provided by the internal carotid and vertebral arteries. The subclavian arteries provide the blood supply for the upper extremity. The celiac, superior mesenteric, suprarenal, renal, gonadal, and inferior mesenteric arteries branch from the abdominal aorta to supply the abdominal viscera. Lumbar arteries provide blood for the muscles and spinal cord. Branches of the external iliac artery provide the blood supply for the lower extremity. The internal iliac artery supplies the pelvic viscera.

Major Systemic Arteries

All systemic arteries are branches, either directly or indirectly, from the aorta. The aorta ascends from the left ventricle, curves posteriorly and to the left, then descends through the thorax and abdomen. This geography divides the aorta into three portions: ascending aorta, arotic arch, and descending aorta. The descending aorta is further subdivided into the thoracic arota and abdominal aorta.

Major Systemic Veins

After blood delivers oxygen to the tissues and picks up carbon dioxide, it returns to the heart through a system of veins. The capillaries, where the gaseous exchange occurs, merge into venules and these converge to form larger and larger veins until the blood reaches either the superior vena cava or inferior vena cava, which drain into the right atrium.

Fetal Circulation

Most circulatory pathways in a fetus are like those in the adult but there are some notable differences because the lungs, the gastrointestinal tract, and the kidneys are not functioning before birth. The fetus obtains its oxygen and nutrients from the mother and also depends on maternal circulation to carry away the carbon dioxide and waste products.

The umbilical cord contains two umbilical arteries to carry fetal blood to the placenta and one umbilical vein to carry oxygen-and-nutrient-rich blood from the placenta to the fetus. The ductus venosus allows blood to bypass the immature liver in fetal circulation. The foramen ovale and ductus arteriosus are modifications that permit blood to bypass the lungs in fetal circulation.

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Often heralded as one of the most important scientific advances in molecular biology, PCR revolutionized the study of DNA to such an extent that its creator, Kary B. Mullis, was awarded the Nobel Prize for Chemistry in 1993.

What is PCR used for?

Once amplified, the DNA produced by PCR can be used in many different laboratory procedures. For example, most mapping techniques in the Human Genome Project (HGP) relied on PCR.

PCR is also valuable in a number of laboratory and clinical techniques, including DNA fingerprinting, detection of bacteria or viruses (particularly AIDS), and diagnosis of genetic disorders. This technique has featured prominently in global testing for the novel Corona Virus (SARS-nCoV2).

How does PCR work?

To amplify a segment of DNA using PCR, the sample is first heated so the DNA denatures, or separates into two pieces of single-stranded DNA. Next, an enzyme called “Taq polymerase” synthesizes – builds – two new strands of DNA, using the original strands as templates.

This process results in the duplication of the original DNA, with each of the new molecules containing one old and one new strand of DNA. Then each of these strands can be used to create two new copies, and so on, and so on. The cycle of denaturing and synthesizing new DNA is repeated as many as 30 or 40 times, leading to more than one billion exact copies of the original DNA segment.

The entire cycling process of PCR is automated and can be completed in just a few hours. It is directed by a machine called a thermocycler, which is programmed to alter the temperature of the reaction every few minutes to allow DNA denaturing and synthesis.

PCR’s role in Covid19 testing

The info-graphic below will help you visualize the testing procedures for Covd19. This article will focus only on the PCR testing and not on the identification of antibodies with Serological Testing. PCR will assess if you are infected, whereas the antibodies test checks to see if you were infected.

The Diagnostic or PCR Test

This test uses a sample of mucus typically taken from a person’s nose or throat. The test may also work on saliva — that’s under investigation. It looks for the genetic material of the coronavirus. The test uses PCR (polymerase chain reaction), which greatly amplifies the viral genetic material if it is present. That material is detectable when a person is actively infected.

Generally speaking, in terms of producing a reliable result, these are the best tests. However, a few days may pass before the virus starts replicating in the throat and nose, so the test isn’t guaranteed to identify someone who has recently been infected. Swabs can also sometimes fail to pick up signs of active infection.

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Red Blood Cells

Red blood cells (RBC) are also called erythrocytes. They deliver oxygen from your lungs to your tissues and organs. Blood cells constantly die and your body makes new ones. Red blood cells live about 120 days. Red blood cells are the most common type of blood cell and your principal means of delivering oxygen to the body tissues—via blood flow through the circulatory system.

The cytoplasm of erythrocytes is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells. Carbon monoxide is so dangerous because it binds far better to hemoglobin than oxygen.

White Blood Cells

White blood cells (WBCs), also called leukocytes or leucocytes. They are a component of the immune system that is involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system. Some white blood cells live less than a day, but others live much longer.

All white blood cells have nuclei, which distinguishes them from the other blood cells, such as red blood cells and platelets. The two main categories of white blood cells are granulocytes and agranulocytes.

Platlets

Platelets, also called thrombocytes, help blood to clot when you have a cut or wound. Bone marrow, the spongy material inside your bones, makes new blood cells. and platelets live about 6 days. Like red cells, platelets have no nucleus. However, unlike red cells that originate in the marrow as nucleated cells and lose their nucleus, platelets are produced by budding off from a giant multi nucleated marrow cell called a megakaryocyte.

Blood Plasma

Blood plasma is the pale yellow colored liquid component of blood that normally holds the blood cells in whole blood in suspension. It makes up about 55% of the body’s total blood volume. It is the intravascular fluid part of extracellular fluid (all body fluid outside of cells).

It is mostly water (up to 95% by volume), and contains dissolved proteins (6–8%) (i.e.—serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (Na+, Ca2+, Mg2+, HCO3−, Cl−, etc.), hormones, and carbon dioxide . Plasma also serves as the protein reserve of the human body. It plays a vital role in an intravascular osmotic effect that keeps electrolytes in balanced form and protects the body from infection and other blood disorders.

How Blood is Typed (classified)

Blood types are determined by the presence or absence of certain antigens – substances that can trigger an immune response if they are foreign to the body.  Since some antigens can trigger a patient’s immune system to attack the transfused blood, safe blood transfusions depend on careful blood typing and crossmatching.

There are four major blood groups determined by the presence or absence of two antigens – A and B – on the surface of red blood cells. In addition to the A and B antigens, there is a protein called the Rh factor, which can be either present (+) or absent (–), creating the 8 most common blood types (A+, A-, B+, B-, O+, O-, AB+, AB-).

We use one of two systems to classify blood, the ABO system or the Rh System. The Rh System simply classifies you as being Rh+ or Rh-. Being positive means simply your blood has the Rh protein antigen, being negative indicates the protein antigen is not present in your blood. The ABO system identifies the presence, or absence, of A,B, AB antigens in your blood

• Donors with blood type A… can donate to recipients with blood types A and AB
• Donors with blood type B… can donate to recipients with blood types B and AB
• Donors with blood type AB… can donate to recipients with blood type AB only
• Donors with blood type O… can donate to recipients with blood types A, B, AB and O (O is the universal donor: donors with O blood are compatible with any other blood type)

Rh-negative blood is given to Rh-negative patients, and Rh-positive or Rh-negative blood may be given to Rh-positive patients. The rules for plasma are the reverse. Things become more complicated with the addition of the Rh Factor protein. the info-graphic provided below expands the full combinations of the donor/ recipient relationship.

Note: The universal red cell donor has Type O negative blood.The universal plasma donor has Type AB blood.

Prevalence of Blood Types Globally

Just how widespread are certain blood types within the general population? AB- is by far the rarest. Refer to the info-graphic below for other blood types.

Inheriting Blood Types

Like eye color, blood type is passed genetically from your parents. Whether your blood group is type A, B, AB or O is based on the blood types of your mother and father. This makes blood typing an integral part of paternity suits. The table below will explain the combinations in more detail.

Note: If you have questions about paternity testing or about blood group inheritance, your primary care physician should be able to provide you with an appropriate referral. Testing difficulties can cause exceptions to the above patterns. ABO blood typing is not sufficient to prove or disprove paternity or maternity.

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