Week 10 Flashcards
Blood testing
Proteins -> ELISA
Enzyme-linked immunosorbent assay
Antibody-Antigen binding reactions
DNA/RNA -> NAT
Nucleic acid amplification test
Polymerase chain reaction (PCR) based, typically
DNA hybridization and sequencing techniques also available
Staining, microscopy, flow cytometry
Analytical chemistry, e.g. chromatography, spectrometry, nephelometry, fluorimetry, solid-state analyzers, etc.
Bacterial cultures and typing
Is blood a perfect window into our health?
Many biomarkers of health and disease may be found in blood
A biomarker is a measurable biological variable that correlates with some other parameter of health. A biomarker may be a determinant or a consequence
New biomarkers in blood seem to be announced every month
Smaller, faster, automated, ‘ubered’
Theranos Inc., ‘Lab on a chip’
Personal use? How reliable or valid?
The accuracy and validity of this technology was eventually found to be fraudulent (CEO and COO both found guilty on multiple counts)
Environmental exposures and exogenous agents in our blood
Consider ADME principles (absorption, distribution, metabolism, and excretion)
How many things enter our body and have an impact on our health?
Most will show up in our blood in one form or another
Consider lead (Pb) poisoning, which can happen at extremely low levels
-current Canadian blood lead intervention level of 10 μg/dL, yet health effects may even be found with 1-2mg/dL
A more recent example: polyfluoroalkyl substances (PFAS)
Found in many items to give it a non-stick, hydrophobic surface
-Non-stick cookware
-Stain-resistant fabrics
-Water-resistant/proof clothing
-Food packaging
Designated by some as a ‘forever’ chemical since they resist breakdown or metabolism in biological systems
Cholesterol and coronary artery disease
-cholesterol dual role, essential for health + risk factor for CVD
-high levels of cholesterol can lead to death
-HDL high density lipo protein = good and LDL = bad, plaque formation in arteries
-High LDL low HDL = risk factor for heart disease
Blood tests
-levels of insulin can impact glucose, fasting before can impact glucose + cholesterol
-normal range not just specific number
-glucose measurement can still be biased by fasting
-assess heart disease risk factor
-15% risk of CVD in 10 yrs
-lifestyle changes i.e. diet, exercise, quitting smoking
Blood technology
Wearable, non-invasive devices
Measuring pulse or heart rate
Measuring oxygenation
New technologies are aiming at measuring blood pressure, arrhythmias, blood glucose, and more
Concerns over accuracy, privacy, utility of the information
e.g. oxygen: pulse oximeter measures oxygen saturation or continuous glucose monitors for diabetes management
Circulating HSCs
(hematopoietic stem cells)
Not abundant, but they have been identified
HSCs with gene therapy applied
e.g. sickle cell anemia treatment
Convalescent plasma
Circulating antibodies that can provide passive immunity to a recipient
e.g. ebola, covid
also fountain of youth factors
Blood component therapy
-whole blood for major trauma, severe bleeding
-RBCs for anemia
-plasmapheresis: fraction plasma obtain albumin etc. used in autoimmune diseases, to remove harmful substances in blood
The Edwin J. Cohn plasma fractionation method
-fraction 1 or fibrinogen essential for blood clotting
-fraction 2 and 3 antibodies for immune therapy
-Fraction 5 used for burns, liver and diseases
Blood Doping
Also known as blood boosting, it is generating an increase in RBC and Hb levels by several methods, used by athletes to perform better through O2 delivery
-Autologous transfusion: Removing, storing, and reinfusing your own blood before competition
-Homologous transfusion: transfusion of a matched blood type from someone else (less common)
-EPO injections: Recombinant human erythropoietin (rhEPO) or related synthetic mimics
–First developed and licensed for clinical treatment of anemia
-EPO: hormone stimulates RBC production
Increases oxygen carrying capacity, measured in a value called VO2max (maximal oxygen uptake)
VO2max
VO2max is a value corresponding to uptake, transport, and maximal use of O2 by muscles. It is variable and aerobic training can increase it by up to ~35%. This is driven by increased cardiac output and oxygen carrying capacity in the blood. Blood doping may be able to drive the VO2max value up by 5-10%.
Blood Doping History, briefly
Attention towards blood was raised during 1968 Mexico City Summer Olympics, as high-altitude location was attributed to differences in performances
Doping by transfusions probably started among endurance athletes in 1970s
First documented case in 1984
-US cycling team, LA Olympics
Cycling had most cases, but it also showed up in cross country skiing, long distance runners
Late 1980s see the advent and proliferation of rhEPO use
1999 to 2005, Lance Armstrong wins seven consecutive times at the Tour de France
Lance Armstrong stripped of these seven titles in 2012
Many athletes from 2014 and 2018 Olympics had medals stripped, many were banned from competing and in 2019 Russia was banned from International sports competition for 4 years
Blood Doping: A Plan
-calculated doping regime, avoiding detection while maximizing performance carefully timed blood withdrawals and retransfusion
Blood doping issues
Health consequences
Polycythemia or erythrocytosis: a condition of increased RBC (or hematocrit) and increased blood viscosity
Higher blood pressure and extra workload on the heart
Higher risk of thrombosis (blood clotting) and myocardial infarctions (heart attacks)
Fairness
What training methods, supplements, diets, prosthetics are fair to use?
What is natural?
Is it available to everyone?
Blood doping regulation/monitoring
Blood transfusions first banned in 1986 by IOC: International Olympics Committee
WADA: World Anti-doping Agency
Founded 1999
Clearly still happening in sports
Detection of illicit agents in the blood or urine
Non-glycosylated and differently charged forms of rhEPO
Antibody response to synthetic EPOs
Blood bag plasticizers, such as phthalates
New synthetic hemoglobin
‘Athlete Biological Passport’
Range of blood and other parameters
Individualized and derived over a longitudinal dataset to derive ‘personal reference levels’
stats analysis catch blood doping
-gene doping detecting
-AI based doping detecting
Athlete Biological Passport’
Hematological Module (blood)
Hematocrit (HCT)
Hemoglobin (HCB)
Red blood cell count (RCB)
Reticulocyte count (RCT#)
Reticulocyte % (RCT%)
Immature reticulocyte fraction (IRF)
Mean corpuscular volume (MCV)
Mean corpuscular hemoglobin (MCH)
Mean corpuscular hemoglobin concentration (MCHC)
Red blood cell distribution width standard deviation (RDW-SD)
Steroidal Module (urine)
Testosterone (T)
Epitestosterone (E)
Testosterone/epitestosterone ratio (T/E)
Androsterone (A)
Etiocholanolone (Etio)
5a-androstane-3a,17b-diol (5aAdiol)
5b-androstane-3a,17b-diol (5bAdiol)
4 general outcomes from testing:
normal pattern
suspicious (suspicious results don’t always mean doping but athletes can be flagged, further investigation)
prohibited substance/method
pathological condition
Athlete Biological Passport Impact
after athletes knew detectable through biological passport, stats changed, significantly reduced blood doping in cycling, abp effective deterrent
