1. AQT90 FLEX parameters
27/11/2018

2. In the waiting room
Emergency

3. AQT90 FLEX parameters Infection marker Cardiac markers CRP Myoglobin
Hemostasis marker
D-dimer
Pregnancy marker
ßhCG
Cardiac markers
Myoglobin
CKMB
Troponin I
NT-proBNP
Cardiac markers: Are all proteins. When a cardiac muscle cell dies, the content inside the cell (cardiac markers etc.) is released into the blood stream where we can measure them. Guideline: 30 minutes after arrival to the hospital, the diagnose AMI have to be established and treatment initialized (of course, if the patient suffers from a heart attack). Time = muscle. From Central lab it can easily take 2 hours before the doctor receive the answer of an acute blood sample. There might be many acute tests in central lab and the central lab staff don’t know which sample is the most acute. AQT90 FLEX can give the answer within 18 minutes which match the guidelines perfectly.
Why do we have 3 parameters that all tell about AMI? Because they have a different “increase and decrease pattern” after an AMI. Myoglobin is the first parameter to reach the blood stream, but it’s not so specific. TnI is a late marker and it takes 4-6 hours before we can measure it in the blood after an AMI. But TnI is a very heart specific marker. So to be able to establish a fast and correct diagnose, it’s an advantage to have more than one marker. TnI is seen as the best marker of AMI due to the high specificity.
Infection marker: One of the most frequent tests in the hospital. If you know the body temperature of the patient and the CRP level, you have a good indication of the patient’s condition. You can use CRP to distinguish between viral and bacterial infection. If you have a patient with fever and low CRP it’s probably a viral infection whereas if you have fever and high CRP it’s most likely a bacterial infection.
D-dimer: All persons will always have some D-dimer in the blood. Every time we hurt ourselves and get a small bruises, the body will build a small blot clot to stop the bleeding. When this blood clot is broken down again, D-dimer will be a part of this breakdown process. That means that we only find D-dimer if there has been a blood clot. That’s also why we can use D-dimer to rule out diseases caused by excessive clotting. Negative D-dimer = rule out diseases due to excessive clotting.
hCG: A hormone that supports pregnancy in the early weeks of pregnancy. hCG is responsible for the nausea that many women discover during pregnancy! Many women are admitted to the hospital because of abdominal pain. Just from looking at the woman, it can be very difficult for the doctor to tell what’s wrong. If hCG is negative, it rules out ectopic pregnancy. If we have a unconscious woman after e.g. trauma, it’s extremely important that we find out if she’s pregnant so we can treat her with the right medicine, x-ray etc.
By having all the parameters it’s possible to rule out many dangerous diseases and conditions and the doctor can confirm the first diagnose that maybe was establish before the answers from the blood sample was ready.

4. The patient in the hospital
Patient with heart conditions
Treatment and monitoring of heart conditions
Cardiac markers
Patient
Diagnosis based on:
Clinical assessment
Biochemical tests
Other tests
Patient with sepsis
Treatment and monitoring of sepsis
Infection markers
Patient with coagulation disturbances
Treatment and monitoring of coagulation disturbances
Hemostasis markers
Patient with other problems

5. AQT is only a piece in the puzzle

6. The blood supply to the heart muscle
The heart muscle does not
receive any nutrients or oxygen
from the blood in the heart
chambers
The heart receives
oxygen and nutrients
from the blood in the
coronary arteries
(Source: heartPoint)
The heart is divided into two sides to keep the arterial and the venous blood from mixing. Each side has an upper half (the atrium) which works as a "priming pump" to fill the much stronger lower half (the ventricle) which does the harder pumping. The function of the right side of the heart is to receive deoxygenated blood, in the right atrium, from the body. Then pump it, via the right ventricle, into the lungs so that carbon dioxide can be dropped off and oxygen picked up. The left atrium receives oxygenated blood from the lungs, and the left ventricle pumps it out to the body. On both sides, the lower ventricles are thicker and stronger than the upper atria.
Typically, there is one artery on the right side and one on the left, with the left one generally being the larger. The Left Main coronary artery divides into two sizable branches, the Left Anterior Descending (supplying the front of the heart) and the Left Circumflex (wrapping around the left side and back of the heart). The Right Coronary Artery supplies the back of the heart.

7. Acute myocardial infarction (AMI)
Obstruction of the coronary artery
Lack of oxygen to the cardiac muscle
Muscle-cell degradation and
loss of function
Acute myocardial infarction is a disease that occurs when the blood supply to a part of the heart is interrupted, causing death of heart tissue.
Deprives the heart muscle of oxygen and results in injury to the heart muscle. When a muscle cell dies it can not function. If the area where the cell degradation has occurred is big, the heart function will be impaired and the patient is in risk of dying from the heart attack.
If blood flow is not restored within min, irreversible damage begin to occur. If restored within 3 hours – avoid worse damage. Continue to die 6-8 hours = heart attack complete.
Time = muscle Quick treatment essential
AMI has traditionally been diagnosed on the basis of physical symptoms, typical electrocardiogram (ECG) pattern and cardiac marker measurements. Problems of the traditional approach:
sensitivity problems of ECG (positive in ~30-50 % of MI cases)
AMI not only cause of chest pain
old and non-specific markers (LDH, CK, CK-MB activity)
Intensive research has been ongoing during the last decades to find better diagnostic methods: Troponin, CKMB and myoglobin.
The ACC and AHA have developed performance guidelines for the treatment of MI, stating that patients should receive fibrinolysis within 30 minutes of arrival to the hospital. Patients diagnosed with ST elevation MI are to receive coronary intervention within 90 minutes of arrival to the hospital, this has changed from the 120 minute JCAHO and CMS measures previously in place. A little bit of blockage is generally harmless.
If the vessel becomes narrowed by 50% or so, there can be less blood flow than needed at periods of increased need, such as exercise.
When the vessel is narrowed 90%, there is the potential for lack of blood supply at rest. When the vessel becomes 100% closed, a heart attack generally occurs. If the vessel closes gradually, the muscle may obtain flow from other vessels ("collateral circulation") and "doing its own bypass"

8. Cardiac marker release
The patient discover chest pain. The dying cardiac cells release their content to the bloodstream.
There are different kind of cardiac markers. Together they can tell us whether there has been a heart attack and how serious it is.
These parameters will increase and decrease within a certain timeframe.
A quick treatment is essential for the patients and that’s why we need STAT parameters.
CK-MB, Troponin, and Myoglobin aid in a faster diagnosis which leads to more efficient and effective treatment.

9. Clinical application of troponin I
Troponin I is a late but very sensitive and specific indicator of damage to the heart muscle
Troponin I is used to determine whether the patient has suffered from an AMI
Troponin results must be taken in context with the patient's clinical circumstances.
A positive troponin test at any time indicates the need for detailed investigation of the cardiac status of the patient.
A negative troponin test can only be used to indicate low risk of subsequent cardiac event if the measurement has been made longer than 6 hours after the onset of chest pain. Negative values longer than 12 hours after onset of pain are more reliable.

10. Clinical application of myoglobin
Myoglobin testing is used to help rule out a heart attack
High levels of myoglobin usually require the use of other tests such as CKMB or troponin I to tell whether the damage is to heart or to other skeletal muscles
When myoglobin rises, this means that there has been very recent injury to the heart or other muscle tissue. If myoglobin does not increase after about 5 hours, a heart attack is very unlikely, unless the chest pain started more than a day before.
Because the kidneys remove myoglobin from the blood, myoglobin levels may be high in persons whose kidneys are failing.
Also relevant for trauma patients due to the release in muscles injury.

11. Clinical application of CKMB
CKMB level is tested to:
Diagnose a heart attack
Detect reinfarction
(Source: Creatine Kinase-MB: Dectection of Myocardial Infarction and Monitoring Reperfusion, Journal of Clinical Immunoassay, Volume 17, Number 1, Spring 2004).
According to international guidelines CKMB can be used as a substitute for troponin in the diagnosis of AMI, in case
troponin is not available.

12. Congestive heart failure (CHF)
If the right side of the heart fails, fluid will accumulate in the body, causing swelling of the ankles and legs, along with discomfort in the abdomen
If the left side of the heart fails, the blood will accumulate in the lungs, resulting in pulmonary edema
Normal heart
Heart failure
The heart has been enlarged due to extra workflow in the heart. The enlarged heart is unable to work the way it’s suppose to.
The insufficiency - right side, left side or both sides. Depending on the sides and the severity the symptoms differ.
A person with a right side heart failure is frequently fatigued and may loose weight.

13. Clinical application of BNP/NT-proBNP
BNP/NT-proBNP may be ordered to:
Diagnose heart failure
Grade the severity of the heart failure
An accurate diagnosis is important because heart failure
can be successfully managed with various medical
treatments.
It has been found that high BNP predicts an increased risk of death or subsequent heart attack in patients with acute coronary syndromes.
BNP/ NT-proBNP has a very high negative predictive value (almost 100%) meaning that the test can be used to rule out CHF. If the patient does not have elevated levels of BNP/ NT-proBNP it’s very unlikely that the patient suffer from CHF. If the patient has elevated BNP/ NT-proBNP levels there is need for further investigation i.e. ultrasound of the heart to determine whether the patient has CHF or not.

14. The hemostatic system
The hemostatic system maintains the balance between
bleeding and building a thrombus in the body
If there are disturbances in the haemostatic system the patient will have either a bleeding disorder or excessive clotting which can lead to thrombus formation
In response to injury, this equilibrium ensures local hemostasis without uncontrolled propagation of thrombus. The scale will tip up and down.
There will be small bleedings and to stop that the body will build small thrombus. This is happen all the time and is perfectly normal. In the minute a thrombus is starting to build up there will be a breakdown of the clot. So the build up and the breakdown will proceed simultaneous.
Thrombus formation
Bleeding

15. What is deep vein thrombosis (DVT)
DVT involves clot formation in the deep veins of the body, most frequently in the legs 
These clots may grow very large and block the blood flow in the legs
Symptoms of DVT: Leg pain, tenderness, swelling, discoloration, edema.

16. Pulmonary embolism (PE)
An embolism occurs when propagating blood clots break loose and follow the bloodstream until the blood vessels are so small that the embolism will get stuck and block the blood passage
The most common type of PE is a thrombus that has formed in the leg- or pelvic vein. The embolism is transported in the vein to the lung.
PE is a common and lethal problem. 3. most common cause of death in the US. 650,000 per year. 10 % within an hour.
Symptoms of PE: Shortness of breath, coughing and lung-related chest pain.

17. Clinical application of D-dimer?
D-dimer has a high negative predictive value, i.e. it can be
used to rule out diseases caused by excessive clotting:
Deep vein thrombosis, DVT
Pulmonary embolism, PE

18. Infection Infection is a disease caused by microorganisms like
bacteria's, viruses or fungi
There are many different kinds of infection, e.g:
Sepsis
Pneumonia
Wound infection
Influenza
Cold
We use CRP to detect an infection in the body and to monitor if the treatment against the infection works.
Sepsis is a very common condition in the ICU. Sepsis is a life-threatening condition due to microorganisms in the blood. Without the right treatment and monitoring the patient is in risk of dying. The microorganisms can enter the blood via an infection somewhere in the body or due to a defect skin or mucosa barrier. Earlier identification of sepsis will allow for earlier and more effective treatment for sepsis, as well as shortened duration of illness.

19. Sepsis Sepsis is a deadly form of blood poisoning
1,400 people die worldwide due to sepsis – every day!
The microorganisms can enter the blood via an infection in the body or because of a defect skin or mucosa barrier
Sepsis may lead to multiple organ failure and death
Mortality rate of ~ 30 %
Sepsis can strike anyone but is most likely to develop from infections associated with pneumonia, trauma and surgery
Sepsis is caused by the excessive body's response to an infection. Sepsis is a serious medical condition, resulting from the immune response to a severe infection. Sepsis can strike anyone but is most likely to develop from infections associated with pneumonia, trauma, surgery, burns, genetic factors, cancer and HIV.

20. Clinical applications of CRP
CRP is ordered:
When acute inflammation is suspected
To help evaluate chronic inflammation conditions
To determine whether treatment of an inflammatory disease is effective since CRP levels drop as the inflammation subsides
As a very rough indication for heart disease risk
CRP level increases within 6 hours of an acute stimulus, reaching a peak around 50 hours. CRP can increase as much as 1000-fold with inflammation. Reflects the presence and intensity of inflammation or infection. An elevation in CRP is not the diagnostic sign of any one condition, but it will tell you that there is a infection in the body. CRP can also be used for monitoring to see whether the treatment for the infection works. If CRP decreases, the treatment works!
Cardiology diagnostic test:
Arterial damage is thought to result from inflammation due to chemical insults. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very specific prognostic indicator. Also, these values refer only to prolonged elevation, so a single measurement would be meaningless.
C-reactive protein blood test:
Low risk: <1mg/L High risk: >3mg/L

21. Why have a pregnancy marker?
Accurate determination of whether a patient is pregnant or not prior to starting treatment is essential for emergency medicine providers in order to be able to provide the correct care in all situations
Especially when you want an X-ray taken or to start a treatment with a medication known to be dangerous for the fetus
In the US.... If X-ray..... hCG in all female over the age of 12.
4.4 mill patient visit the ER in the US every year with abdominal pain. Not easy to know the root cause just from the clinical symptoms alone.
A βhCG test is applicable in detecting and to rule out diseases related to pregnancy.

22. What is an ectopic pregnancy?
An ectopic pregnancy is a condition where a fertilized egg settles and grows in any location other than the inner lining of the uterus
The vast majority of ectopic pregnancies occur in the fallopian tube (95 %), however, they can occur in other locations, such as the ovary, cervix, and abdominal cavity.

23. Clinical applications of βhCG assays
βhCG can detect an early pregnancy
A negative βhCG level rules out ectopic pregnancy
Ectopic pregnancy: A negative hCG level rules out ectopic pregnancy in women presenting lower abdominal pain of unknown cause. Elevated hCG levels together with lower abdominal pain and no sign of pregnancy on ultra-sound is a sign of ectopic or extrauterine pregnancy.
Symptoms: Patients with an ectopic pregnancy typically have:
Lower back, abdominal, or pelvic pain. Shoulder pain. There may be cramping or even tenderness on one side of the pelvis.
The pain is of recent onset, and often getting worse. Vaginal bleeding may be present.
Ectopic pregnancy is noted that it can mimic symptoms of other diseases such as appendicitis, other gastrointestinal disorder, problems of the urinary system, as well as pelvic inflammatory disease and other gynecologic problems.
Diagnosis: An ectopic pregnancy has to be suspected in any woman with lower abdominal pain and/or unusual bleeding who is sexually active and whose pregnancy test is positive. And abnormal rise in blood hCG levels may also indicate an ectopic pregnancy. An ultrasound examination may reveal the abnormal location of the pregnancy, show evidence of intraabdominal bleeding, or reveal an empty uterine cavity when normally the pregnancy should have been detectable within the uterus.
Nonsurgical treatment: Early treatment of an ectopic pregnancy with the drug methotrexate has proven to be a viable alternative to surgical treatment since If administered early in the pregnancy, methotrexate can disrupt the growth of the developing embryo causing the cessation of pregnancy.
Surgical treatment: If hemorrhaging has already occurred, surgical intervention is necessary to halt blood loss and reduce the risk of shock. Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy). The first successful surgery for an ectopic pregnancy was performed by in The chance of future pregnancy depends on the status of the tube(s) that are left behind, but is decreased. Often, patients may have to resort to IVF to achieve a successful pregnancy.

24. 73-year-old male…
Last week he went on safari in South Africa. On the way back in the plane he discovers pain in his right leg. During last night, sudden chest pain and breathing problems.
Hyperventilation
Cold skin, pale
Low blood pressure
Pulse 105
ECG shows right-heart
stress

25. Blood gas pH 7.22 ↓ pO2 6.7 kPa/ 50 mmHg ↓ pCO2 3.3 kPa/ 25 mmHg ↓
Hb 8.5 →
sO % →
Lactate 4.5 ↑

26. ?

27. Which parameters? Myoglobin CKMB Troponin I NT-proBNP D-dimer CRP
Elevated D-dimer might be DVT or pulmonary embolism.

28. Pulmonary embolism D-dimer and blood gas support diagnosis
CT scan shows big blood clot in right lung artery
Treatment
Thrombolysis (breakdown of blood clots) Heparin for six months

29. What if... Myoglobin CKMB Troponin I NT-proBNP D-dimer CRP
When the three cardiac markers are increased, it’s a sign of AMI.

30. What if... Myoglobin CKMB Troponin I NT-proBNP D-dimer CRP
Increased CRP indicates an infection. Together with shortness of breath it might be pneumonia.

31. AQT90 FLEX parameters Infection marker Cardiac markers CRP Myoglobin
Hemostasis marker
D-dimer
Pregnancy marker
ßhCG
Cardiac markers
Myoglobin
CKMB
Troponin I
NT-proBNP