BRIDGING PBL

MIDTERM EXAM

NAME: AHMAD SOBOH

SEMESTER V

GROUP 3

PASSPORT NO.: 31749438

E-MAIL: ASOBOH@NEWVISION.GE

DOCTOR: TAMAR VALISHVILI

CASE: ANNA SHAFFER

SENDING DATE: 15/11/2021

2021-2022
PATIENT PRESENTATION

Anna Shaffer – 46 year old woman is brought by her husband of the hospital
.emergency department
.She has an acute pain in her chest and difficulty breathing
.The nurse takes her to the ward immediately and calls for the doctor
While attaching the monitors and the ECG wires, she asks about the medical
.history 1
 Key information:
 Name: Anna Shaffer
 Age: 46-year-old
 Gender: Female
 She is brought to the hospital emergency department by her husband.

Symptoms:
 Acute pain in her chest
 Difficulty breathing

What could be wrong with this lady? Your hypothesis

 Many factors can cause an acute pain in the chest and difficulty
breathing.

Chest pain
No. Hypotheses Process Associated Symptoms
Cardiovascular
Temporary myocardial ischemia,
Sometimes dyspnea,
1. Angina Pectoris usually secondary to coronary
nausea, sweating
atherosclerosis.
Prolonged myocardial ischemia, Dyspnea, nausea,
2. Myocardial Infarction resulting in irreversible muscle vomiting, sweating,
damage or necrosis. weakness
Seen in autoimmune
Irritation of parietal pleura adjacent disorders, postmyocardial
3. Pericarditis
to the pericardium. infarction, viral infection,
chest irradiation

A splitting within the layers of the If thoracic, hoarseness,

4. Aortic Dissection aortic wall, allowing passage of dysphagia; also syncope,
blood to dissect a channel. hemiplegia, paraplegia

Pulmonary
Inflammation of the parietal pleura,
as in pleurisy, pneumonia,
5. Pleuritic Pain Of the underlying illness
pulmonary infarction, or neoplasm;
rarely, subdiaphragmatic abscess
Gastrointestinal and Other
6. Gastrointestinal Reflux Irritation or inflammation of the Sometimes regurgitation,
Disease esophageal mucosa due to reflux of dysphagia; also cough,
gastric acid from lowered laryngitis, asthma

2
 esophageal sphincter tone
Diffuse Esophageal Motor dysfunction of the
7. Dysphagia
Spasm esophageal muscle
Chest Wall Pain, Variable, including trauma,
8. Often local tenderness
Costochondritis inflammation of costal cartilage
Breathlessness,
9. Anxiety, Panic Disorder Unclear palpitations, weakness,
anxiety
Dyspnea
Elevated pressure in pulmonary
capillary bed with transudation of Often cough, orthopnea,
fluid into interstitial spaces and paroxysmal nocturnal
10. Left-Sided Heart Failure
alveoli, decreased compliance dyspnea; sometimes
(increased stiffness) of the lungs, wheezing
increased work of breathing
Chronic productive
Excessive mucus production in
cough, recurrent
11. Chronic Bronchitis bronchi, followed by chronic
respiratory infections;
obstruction of airways
wheezing may develop
Overdistention of air spaces distal
Chronic Obstructive to terminal bronchioles, with
Cough, with scant mucoid
12. Pulmonary Disease destruction of alveolar septa,
sputum
(COPD) alveolar enlargement, and limitation
of expiratory air flow
Reversible bronchial
hyperresponsiveness involving
Wheezing, cough,
13. Asthma release of inflammatory mediators,
tightness in chest
increased airway secretions, and
bronchoconstriction
Abnormal and widespread
Often weakness, fatigue;
Diffuse Interstitial Lung infiltration of cells, fluid, and
14. cough less common than
Diseases collagen into interstitial spaces
in other lung diseases
between alveoli; many causes
Infection of lung parenchyma from Pleuritic pain, cough,
15. Pneumonia the respiratory bronchioles to the sputum, fever, though
alveoli not necessarily present
Leakage of air into pleural space
Spontaneous through blebs on visceral pleura,
16. Pleuritic pain, cough
Pneumothorax with resulting partial or complete
collapse of the lung
17. Acute Pulmonary Sudden occlusion of part of Often none; retrosternal
Embolism pulmonary arterial tree by a blood oppressive pain if
clot that usually originates in deep massive occlusion;
veins of legs or pelvis pleuritic pain, cough,
syncope, hemoptysis,
and/or unilateral leg

3
 swelling and pain from
instigating deep vein
thrombosis; anxiety
Overbreathing, with resultant Sighing, lightheadedness,
Anxiety with respiratory alkalosis and fall in numbness or tingling of
18.
Hyperventilation arterial partial pressure of carbon the hands and feet,
dioxide (pCO2) palpitations, chest pain

What further questions would you ask about the pain?

"SOCRATES"
 Where is the pain?
S Site
 Can you point to where you experience the pain?
 Did the pain come on suddenly or gradually?
 When did the pain first start?
O Onset  Did the pain come on at rest or whilst you were exerting
yourself?
 How long did the pain last for?
C Character  How would you describe the pain?
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  Is the pain constant or does it come and go?
 Does the pain spread elsewhere?
R Radiates  Does it radiate into the neck, shoulder, back, or down your
arm?

 Please tell me about any symptoms you might be having in

your chest
 Are there any associated symptoms other than shortness
Associated
A of breath such as sweating, palpitations, or nausea?
Symptoms
 Have you noticed anything else that accompanies it?
 Are there any other symptoms that seem associated with
the pain?
 How has the pain changed over time?
 When did (does) it start?
T Time  How long does it last?
 How often does it come?
 Does it ever wake you up at night?
 Is there anything that makes it better or worse?
E Exacerbating  Is the pain related to exertion?
 What kinds of activities bring on the pain?
S Severity  How intense is the pain, on a scale of 1 to 10?

What further questions would you ask to help make the diagnosis?
 Begin with a truly open-ended question that does not prefigure an answer.
 Please describe the problem that caused you to come in today?
 How has this condition impacted your activities?
 How often does this occur?
 How long has this been occurring?
 Do you have any chest pain with breathing?
 what is the pain like?
→ when does it occur, and what relieves it?
 Do you have a cough?
→ If yes, what does the cough sound like? when does it occur?
 Do you bring up any phlegm when you cough?
 What does the phlegm look like?
5
  Are you ever short of breath?
 Does your shortness of breath occur at rest or with activity?
 Does shortness of breath impacts your daily living?
 Do you have any problems breathing at night?
→ If so, do you use pillows to help you get in a position to
breathe easier?
 Do you have any allergies?
 How does your allergy affect your breathing?
 Do you smoke now or have you ever smoked? If yes, how many
years did you smoke and how many packs of cigarettes did you
smoke daily?
 What kind of work do you do/did you do?
 In your work are/were you exposed to substances such as
asbestos, chemicals, or cigarette smoke?
 Do you have a personal or family history of asthma, tuberculosis,
lung cancer, cystic fibrosis, bronchitis, and emphysema?
 Do you have a personal or family history of any other lung
disease? **

HISTORY OF PRESENTING COMPLAINTS

Anna’s health has been fine.

Three days ago, she has returned from the holiday, which she has spent in
Turkey.
She noticed pain in her right calf five days after her flight in Turkey.
The pain went away itself and she did not pay much attention to this as she
thought that she has sprained the muscle.
During the return flight she felt the pain again, but everything disappeared
while she was coming back home, although she felt the light pain again today.
She woke up in the morning with the pain in left side of her chest.
She tried not to pay attention to this, but at 6 o’clock in the morning she had
to get up and take paracetamol for pain relief. 6
She realised that the pain is less if she straightens her back.
How is the pattern and rate of onset of breathlessness important in narrowing
your hypotheses? (!!!)
 All the hypotheses listed above cause acute dyspnea, which is a
sudden onset of shortness of breath. However, in many conditions
acute dyspnea is preceded by other symptoms which helps us
eliminate some hypotheses. Anna felt at first a pain in her right
calf after 5 days of her flight to turkey. 3 days after coming back
she had a chest pain, knowing that she felt the pain again in her
calf muscle. This information helps us eliminate some hypotheses:
1. GERD: Anna didn’t mention the sensation of a heartburn.
Moreover, the shortness of breath in this case occurs due to
dysphagia. Those are the primary symptoms of GERD so this
hypothesis can be eliminated.
2. Anemia: this condition causes mainly fatigue, weaknesses,
irregular heart beats and a pale skin before the onset of
shortness of breath, which Anna wasn’t experiencing.
3. Bronchitis: it is characterized by coughing (the cough may
contain mucus that is clear, white, yellow or green) and a
chest congestion before the onset of breathlessness.
 Acute dyspnea might be caused by an infection, asthma,
pneumothorax, a pulmonary embolism, lung cancer, COPD, a
congestive heart failure, rib fracture, pleuritic or pericarditis.
 However, the pattern of onset of her breathlessness (the one that
is related to the pain felt in the calf) helps us narrow down the
hypotheses and focus on the one concerning the pulmonary
emboli.

7
Is the calf pain important? Explain (!!!)
 Yes, of course
 Calf pain is important to help us to detect some diagnoses, such as:
1. Arterial ischemia
2. Peripheral Arterial Disease
3. Deep Venous Thrombosis (DVT)
4. Compartment Syndrome
5. Muscle cramp
6. Muscle strain

PIC 1

Do you know of any decision making tools that help doctors decide the
likelihood of the calf pain being a DVT?
 DVTs often have no demonstrable signs, so diagnosis often
depends on clinical suspicion and testing.
→ Palpate for any venous tenderness or cords, which can
accompany a DVT
 With the patient’s leg flexed at the knee and relaxed, palpate the
calf. With your fingerpads, gently compress the calf muscles
against the tibia, and search for any tenderness or cords.
→ Only half of patients with DVT in the calf have tenderness or
venous cords, and absence of calf tenderness does not rule
out thrombosis.
 Homans’ sign
→ It might be also used for the diagnosis of DVT.

8
 → Anna should be in a supine position, then the doctor should abruptly
dorsiflex her ankle. If she reports any pain in her calf or popliteal
region, then it indicates a positive sign which is caused by a thrombus.
 Venography
→ Most accurate test for diagnosis of DVT of calf veins
→ Invasive and infrequently used
→ Allows visualization of the deep and superficial venous systems,
and allows assessment of patency and valvular competence
 D-dimer testing
→ Has a very high sensitivity (95%), but low specificity (50%); can be used
to rule out DVT when combined with Doppler and clinical suspicion
→ D-dimer blood test reveals if blood clots are formed in Anna’s body.

A B

PIC 2

Homans Sign
(A) Dorsiflexion of the foot with the knee extended.
(B) Dorsiflexion of the foot with the knee flexed. PIC 3

Homans Sign is positive if pain is occurring upon CT venography of normal veins and DVTs.
dorsiflexion of the foot with the knee extended and flexed Veins in panel 1a are normal, while multiple
indicating deep vein thrombosis (DVT). DVTs are seen in panel 1b (intraluminal filling
defects indicating DVTs are shown by the
arrows).
What could happen to a clot in the leg?
 Damage to the veins from the blood clot reduces blood flow in the affected
areas, causing leg pain and swelling, skin discoloration and skin sores.

PIC 4

Symptoms of DVT (blood clot in the leg)

include swelling, pain, redness, warmth to
the touch, leg cramps, or bluish/whitish 9
discoloration of the skin.
  Although the incidence of pulmonary embolism is low in calves, it can still
occur in an Anna's case due to the development of calf vein thrombus.
 Also, a clot in a leg artery can cause its obstruction and results in a
gangrene necrosis.

Does this information support any of your hypotheses?

 This information is very useful in the diagnosis of Anna, because it
confirms the formation of a blood clot in her leg which then
caused a pulmonary embolism.
 This explains her symptoms and helps us rule out other
hypotheses (Angina Pectoris, Myocardial Infarction, Pericarditis, Aortic
Dissection, Gastrointestinal Reflux Disease, Diffuse Esophageal Spasm,
Chest Wall Pain, Costochondritis, Anxiety, Panic Disorder, Chronic
Bronchitis, COPD, asthma, and Diffuse Interstitial Lung Diseases.)
 And this makes us close to diagnosis of Pulmonary Embolism, DVT,
and may be Anxiety with Hyperventilation.

ADDITIONAL HISTORY

The physical examination showed that in general everything is fine (All systems
are normal) except varicose veins on the right leg which appeared during the
pregnancy. Anna does not take any medication, apart from the hormone
replacement therapy, which she was prescribed as she had strong night-time
sweating and copious menstrual bleeding before the menopause. HRT removed
these problems. she does not smoke but drinks 14 units of alcohol a week. She is
allergic to penicillin. Anna is married and she has three sons. She works as a
manager in a nearby polyclinic. Both her parents had deep vein thrombosis.

What new information do you have about patient?

 Anna is married and has 3 sons.

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  Occupation: manager in a nearby polyclinic
 She doesn’t smoke.
 The physical examination reveals that Anna is in a good health and
that all her systems are normal.
 She had varicose veins on her right leg during her pregnancy
 She doesn’t take any drugs, except the hormone replacement
therapy which treated her pre-menopause symptoms (strong
night-time sweating and copious menstrual bleeding).
 She is a heavy drinker, drinking 14 units of alcohol/week .
 She is allergic to penicillin.
 Both of her parents had deep vein thrombosis.

What sort of examination would you do?

 Since DVT is suspected, a D-dimer blood test should be done. This
test will detect either the presence or absence of D-dimer which is
a type of protein produced by blood clots. A normal result on a D-
dimer test ( <0.5 microgram FEU/mL) often can help rule out PE.
However if the D-dimer test value exceeds the normal value
additional tests should be done such as computed tomographic
pulmonary angiography (CTPA) (Discussed later).

Are there risk factors for blood clots in the history?

 Both of Anna’s parents had deep vein thrombosis.
→ The genetic cause of excessive blood clotting is usually not
inherited. Instead, it occurs when the body does not
produce the proper blood proteins.
→ Anna's more likely to have a genetic cause of excessive blood
clotting because she has family members have had DVT.
 Anna had varicose veins on her right leg
→ Deep vein thrombosis (DVT) is a serious condition with blood
clots in the deep veins. This condition does not usually happen
with varicose veins. That is because varicose veins affect the
veins close to the surface of the skin.
→ However, with severe varicose veins, there is a small
chance of developing blood clots in the deep veins. Blood
clots need medical care right away.
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  Anna is a heavy drinker, drinking 14 units of alcohol/week.
→ Too much alcohol increases platelets in the blood, so they
are more likely to clot randomly.
→ Alcohol also activates platelets, meaning they are more
likely to begin forming clots.
 Anna does not take any medication, apart from the hormone
replacement therapy
→ Taking HRT tablets can increase your risk of blood clots -
but this risk is still small
 Anna's pregnancy
→ Pregnancy increases the risk of a DVT, with the highest risk
being just after she has had her baby.
 She noticed pain in her right calf five days after her flight in Turkey.
→ Long airplane flights or multiple flights in a short period can
be associated with deep vein thrombosis (DVT) and
pulmonary embolism (PE).

PHYSICAL EXAMINATION

Oxygen saturation – 93% on air

Unhealthy looking woman.
Shortness of breath at rest, speech is laboured
The breathing process is not normal, with sudden stops for inspiration (because of the
pain)
Temperature 37.2 °C
Cardiovascular system (CVS) – pulse 76 per minute, Blood pressure 142/85
Heart sounds I + II + O
Chest – respiratory rate 25; percussion - Vocal resonance normal, Breath sounds –
vesicular
Abdominal cavity – abdomen is soft, no anomalies.
Legs – Pain in the right calf, no redness or edema. Varicose veins present on the right
leg.

12
What are the main findings on examination?
 Oxygen saturation – 93% on air
→ Normal range is 95%-100%
→ A blood oxygen saturation level less than 95 percent is abnormal.
 Temperature 37.2 °C
→ Normal range is 36-37.5°C
→ Anna has a normal temperature
 Pulse 76 per minute
→ Normal range is 60-100
→ Anna has a normal pulse
 Blood pressure 142/85
→ The first number (systolic) should be between 100 and 120, and the
second number (diastolic) should be between 60 and 80.
→ Anna has stage 1 hypertension
 Heart sounds I + II + O
→ The opening snap (OS) is a very early diastolic sound caused by abrupt
deceleration during the opening of a stenotic mitral valve. It is best
heard just medial to the apex and along the lower left sternal border.
 Respiratory rate 25
→ Normal range is 12-17 per/min
→ Anna had dyspnea
 Percussion - Vocal resonance normal
 Breath sounds – vesicular
→ Duration of vesicular sound: Inspiratory sounds last longer
than expiratory sounds.
→ It is normal
 Abdominal cavity – abdomen is soft, no anomalies.
→ It is normal
 Pain in the right calf, no redness or edema.
 Varicose veins present on the right leg.
How do you interpret these examination findings? Do these findings revise
your hypotheses?
 These examination finding makes me close to diagnosis of
Pulmonary Embolism, DVT.
→ Oxygen saturation level (93%) may be a sign of PE.
→ High blood pressure (142/85), hypertension may be a sign of PE
→ Respiratory rate 25 is a dyspnea, it may be a sign of PE
→ Calf pain may be related to DVT
→ Varicose veins may be related to DVT

What is the most likely diagnosis for the chest pain now?
 To sum up everything till now, Anna first felt a pain in her right
calf and few days later her symptoms started (chest pain and

13
 difficulty breathing). All the additional information given suggest
that the pain in her calf was caused by a thrombus which then
travelled in the blood stream and occluded an artery in the
pulmonary circulation. So, the most likely diagnosis foe her chest
pain is a pulmonary embolism (PE).

What investigations would you perform? (!!!)

 First, Homans’ sign should be performed because it is useful in the
diagnosis of DVT. If Anna feels pain, this will be an indication of DVT
and additional tests should be done to confirm the diagnosis.
 Duplex ultrasonography, the standard imaging test to diagnose DVT, is
an imaging test that uses sound waves to check the flow of blood in the
veins. It can detect blockages or blood clots in the deep veins (PIC 5).
 Computed tomographic pulmonary angiography (CTPA) is a unique
type of X ray test which includes the injection of a contact material
into a vein providing images of the blood vessels in the lungs. CTPA is
the standard imaging test used for the diagnosis of PE. (PIC 6)

PIC 5 PIC 6
Venous duplex ultrasonography indicated absence of blood flow in the
CTPA showing an embolus in the pulmonary artery
thrombosed left femoral vein (solid arrow) and compression of the left
femoral artery (dashed arrow). The diameter of the vein examined was
still considerably What initial
broad when treatment would you
compressed give?
 Supplemental oxygen to correct hypoxemia.
→ Severe hypoxemia or respiratory failure requires intubation
and mechanical ventilation.
 Acute anticoagulation therapy with either unfractionated or low-
molecular-weight heparin to prevent another PE.
→ Anticoagulation prevents further clot formation, but does
not lyse existing emboli or diminish thrombus size.
→ Heparin acts at a number of molecular targets, but its
anticoagulant effect is a consequence of binding to
antithrombin III, with the subsequent rapid inactivation of
coagulation factors.
 Oral anticoagulation with warfarin or one of the novel oral
anticoagulants (e.g., rivaroxaban) for long-term treatment.

14
 FURTHER DEVELOPMENTS

The doctor quickly organises the medical investigation and treatment as Anna
has severe pain.
She is given oxygen and intravenous drip.
Blood samples are taken. ECG is done.
She is connected to the monitor looking at her heart, pulse and blood pressure.
Pulse oximeter is attached to her finger for the control of oxygen saturation.
She is given intravenous morphine for pain relief.
Chest x-ray is done in the emergency department. the doctor analyses the clinical
picture, results of the ECG and the x-ray.
The secondary thromboembolism due to deep vein thrombosis is diagnosed.
Further investigation is planned to confirm the diagnosis.

How might a clot in the deep vein of the legs lead to a pulmonary embolus?
 A pulmonary embolism (PE) occurs when a blood clot from a deep
vein (a DVT) detaches from a vein (embolizes), travels through the
right side of the heart, and becomes lodged as an embolus in a

15
 pulmonary artery that supplies deoxygenated blood to the lungs
for oxygenation.
 Depending on its size, a PE can occlude the main pulmonary
artery, lodge at the bifurcation of the right and left pulmonary
arteries (saddle embolus), or pass into the smaller, branching
arterioles. (PIC 7)

PIC 7
This picture illustrates how a DVT
can result in a PE

What pathological changes occur during lung infarction?

 Lung infraction or Pulmonary infarction occurs if a large- or
medium-sized artery is obstructed in patients with pre-existing
cardiopulmonary compromise; only 10% of PEs cause infarction.
→ Presents with shortness of breath, hemoptysis, pleuritic
chest pain, and pleural effusion
→ V/Q lung scan shows mismatch; perfusion is abnormal.
→ Spiral CT shows a vascular filling defect in the lung.
→ Lower extremity Doppler ultrasound is useful to detect DVT.
→ D-dimer is elevated.
→ Gross examination reveals a hemorrhagic, wedge-shaped infarct.

How often does PE occur after DVT?

 48 per 1,000 for DVT and 69 per 1,000 for PE. According to US Census
Bureau, the population of approximately 300 million Americans suggests
that more than 350,000 individuals are affected by DVT/PE each year.

16
Are there other kinds of emboli?
 There are different types of embolism classified based on the embolic
material:
1. Thromboembolism - embolism of thrombus or blood clot.
2. Fat embolism - embolism of fat droplets.
3. Air embolism (also known as a gas embolism) - embolism of air
bubbles.
4. Septic embolism - embolism of pus containing bacteria.
5. Tissue embolism - embolism of small fragments of tissue.
6. Foreign body embolism - embolism of foreign materials such as
talc and other small objects.
7. Amniotic fluid embolism - embolism of amniotic fluid, fetal cells,
hair or other debris that enter the mother's blood stream via the
placental bed of the uterus and trigger an allergic reaction

How do clots form in the body (clotting cascade)and how are they degraded
(fibrinolytic pathway)?
 Before discussing the clotting cascade, is should be noted that
hemostasis refers to the formation of a blood clot to prevent the extent
of bleeding and involves platelets, clotting factors and the endothelium
that occurs at the site of injury. Moreover, vasoconstriction occurs to
reduce the blood flow to the injured artery and prevent blood loss.
 The coagulation cascade is a series of amplifying enzymatic
reactions that results in the deposition of an insoluble fibrin clot.
- Each reaction step involves an enzyme (an activated coagulation factor), a
substrate (an inactive proenzyme form of a coagulation factor), and a cofactor
(a reaction accelerator). These components are assembled on a negatively
charged phospholipid surface, which is provided by activated platelets.
- The coagulation cascade can be divided into the extrinsic and intrinsic pathways.
1. The extrinsic pathway:
 This pathway is activated through tissue factor released by
endothelial cells after an injury
 Factor VII is only used in the extrinsic pathway
 The prothrombin time (PT) assay checks the functions proteins in
the extrinsic pathway, which are factors VII, X, V, II and fibrinogen
17
  The right side of figure 5-A shows the series of events which
occurs after the activation of the extrinsic pathway
2. The intrinsic pathway:
 This pathway is activated by exposing endothelial collagen
and VonWillebrand factor after an endothelial injury.
 The VonWillebrand factor functions as an adhesion bridge
between the sub-endothelial collagen of the artery and the
glycoprotein Ib (GpIb) found on the platelets.
 Factors of the intrinsic pathway: factors VIII, IX, XI and XII
 The partial thromboplastin time (PTT) assay assesses the
function of proteins in the intrinsic pathway known as
factors XII, XI, IX, VIII, X, V, II and I
 The left side of figure 5-A shows the clotting cascade that
occurs in the intrinsic pathway
- Common factors include factors X,V, II (prothrombin) and I (fibrinogen).
These factors are used in both pathways. In the extrinsic pathway,
activated factor VII (VIIa bound to the tissue factor) activates factor X
which then activates prothrombin to produce thrombin which finally
cleaves fibrinogen to fibrin clot. The same series of events happens in the
intrinsic pathway, the only difference is that activated factor IX activates
factor X.

PIC 8

The coagulation cascade in the laboratory and in vivo. (A) Clotting is initiated in the laboratory by adding
phospholipids, calcium, and either a negative-charged substance such as glass beads (intrinsic pathway) or a
source of tissue factor (extrinsic pathway). (B) In vivo, tissue factor is the major initiator of coagulation, which is
amplified by feedback loops involving thrombin (dotted lines). The red polypeptides are inactive factors, the dark
green polypeptides are active factors, whereas the light green polypeptides correspond to cofactors.

- It should be note that the series of events that occur in vivo are
quite different and is represented. (Picture 8)
- Fibrin plays an essential role during clotting. This insoluble protein is the
result of the clotting cascades (intrinsic and extrinsic). Fibrin molecules
combine together to form long fibrin threads in order to trap platelets

18
 and RBCs, building up a spongy mass that gradually hardens and
contracts to form the blood clot and prevent bleeding.
 The fibrinolytic cascade limits the size of the clot and contributes to its
dissolution. Fibrinolysis is done by converting plasminogen to plasmin,
which breaks down fibrin and interferes with its polymerization. The most
important plasminogen activator is t PA, it is synthesized principally by
endothelium and is most active when bound to fibrin. Once activated,
plasmin is in turn controlled by counter-regulatory factors such as α2-
plasmin inhibitor, a plasma protein that binds and rapidly inhibits free
plasmin. Picture 9 represents the activators and inhibitors of plasminogen.

PIC 9

The fibrinolytic system, illustrating various plasminogen activators and inhibitors

Fibrin (clot) Formation

 The fibrinogen is produced by the cleavage of the polycyclic
peptides to form double-stranded oligomers that can then extend
into protofibrils.

Why do a CXR?
 The healthcare provider may order a chest X-ray to see how well a
heart or lungs are working. Anna may need a chest X-ray, until we rule
out other hypotheses suspected that she has any of the following:
→ Enlarged heart which can mean you have a congenital heart
defect or cardiomyopathy
→ Fluid in the space between your lungs and your chest wall
(pleural effusion)
→ Pneumonia or another lung problem
→ Ballooning of the aorta or another great blood vessel (aneurysm)
→ Broken bone
→ Hardening of a heart valve or aorta (calcification)
→ Tumors or cancer
→ Diaphragm that has moved out of place (hernia)
19
 → Inflammation of the lining of the lung (pleuritis)
→ Fluid in the lungs (pulmonary edema) which can mean you
have congestive heart failure

What does the CXR normally look like in PE?

 The classic radiographic findings of pulmonary infarction include a
wedge-shaped, pleura-based triangular opacity with an apex
pointing toward the hilus (Hampton hump) or decreased
vascularity (Westermark sign). These findings are suggestive of
pulmonary embolism but are infrequently observed.

(!!!)

What are the ECG changes in PE?

 No changes
 S1, Q3, T3
 Tall R waves: V1
 P pulmonale (peaked P waves): inferior leads
 Right axis deviation, Right bundle branch block
 Atrial arrhythmias

20
  T wave inversion: V1, V2, V3
 Right ventricular strain: if identified is associated with adverse
short-term outcome and adds prognostic value to
echocardiographic evidence of right ventricular dysfunction in
patients with acute pulmonary embolism and normal blood
pressure.

LABORATORY FINDINGS
ABG Normal Range
PO2 = 9.6 kPa PaO2 10-13 kPa
PCO2 = 4.5 kPa PCO2 4.9-6.1 kPa
HCO3 = 22 mmol/l HCO3- 22-28 mmol/L
O2 saturation = 93%
CXR ( chest x-ray available separately)
D-dimers 0.8 [0-0.3]
pH 7.35-7.45

How can you interpret these laboratory findings?

ABG Normal Range
PO2 = 9.6 kPa PaO2 10-13 kPa Anna has hypoxemia
PCO2 = 4.5 kPa PCO2 4.9-6.1 kPa She also has hypocapnia
She has a normal level
HCO3 = 22 mmol/l HCO3- 22-28 mmol/L of bicarbonate in her
blood.
Oxygen saturation level
O2 saturation = 93% Normal range is 95%-100%
(93%), it is a sign of PE.
D-dimers 0.8 [0-0.3] <0.5 A positive D-dimer

The pH may be greater

pH 7.35-7.45
than 7.45

What are the possible changes in arterial blood gases?

ABG Normal Range Possible changes
PO2 = 9.6 kPa PaO2 10-13 kPa ↓ PaO2
PCO2 = 4.5 kPa PCO2 4.9-6.1 kPa ↓ PCO2
21
 HCO3 = 22 mmol/l HCO3- 22-28 mmol/L ↑ HCO3
O2 saturation = 93% 95%-100% ↓ O2 saturation
D-dimers 0.8 [0-0.3] <0.5 ↑ D-dimers
pH 7.35-7.45 ↓ pH >7.45

What are D dimers?

 A D-dimer test looks for D-dimer in blood. D-dimer is a protein
fragment (small piece) that's made when a blood clot dissolves in
your body.

What are the features of a test that would help you decide whether D-Dimers
a useful test for clinically suspected DVT?
 The D-dimer test has a high sensitivity (90%) however it has a low
specificity (37.5%). A high D-dimer test may be caused by a
clotting disorder, however it cannot show where the clot is
located or what type of clotting disorder Anna has. Thus, many
conditions can result in a positive D-dimer test result, such as a
recent surgery, trauma, infection, heart attack, stroke and some
cancers or conditions in which fibrin is not cleared normally, such
as liver disease.
 D-dimer is detectable in patients with deep venous thrombosis
(DVT), as it is a marker of endogenous fibrinolysis.

PATIENT MANAGEMENT
Anna is given heparin intravenously and is admitted to the ward. The doctor
explains that after the diagnosis is absolutely confirmed she will be given warfarin.

Why is heparin given and what is its mechanism of action?

 Heparin is an injectable, rapidly acting anticoagulant that is often
used acutely to interfere with the formation of thrombi.
 The realization that low molecular weight forms of heparin
(LMWHs) can also act as anticoagulants led to the isolation of
enoxaparin, produced by enzymatic depolymerization of
unfractionated heparin.
 Mechanism of action: Heparin acts at a number of molecular
targets, but its anticoagulant effect is a consequence of binding to
antithrombin III, with the subsequent rapid inactivation of
coagulation factors. Antithrombin III is an α globulin that inhibits

22
 serine proteases of thrombin (factor IIa) and factor Xa. In the
absence of heparin, antithrombin III Interacts very slowly with
thrombin and factor Xa. When heparin molecules bind to
antithrombin III, a conformational change occurs that catalyzes
the inhibition of thrombin about 1000-fold. LMWHs complex with
antithrombin III and inactivate factor Xa (including that located on
platelet surfaces) but do not bind as avidly to thrombin. A unique
pentasaccharide sequence contained in heparin and LMWHs
permits their binding to antithrombin III.

Why is heparin started before warfarin? What is the mechanism of action of

warfarin?
 Because of the delay in factor II (prothrombin) suppression,
heparin is administered concurrently for four to five days to
prevent thrombus propagation. Loading doses of warfarin are not
warranted and may result in bleeding complications.

FURTHER DEVELOPMENTS
Anna is prescribed heparin therapy with the low-molecular heparin once daily.
Further investigations need to confirm the likely diagnosis.

What other investigations would you consider?

 Now that everything looks like Anna has a pulmonary embolism,
further imaging test should be done to confirm her diagnosis. ↓

Further radiological investigations to confirm diagnosis of PE:

1. Computed tomographic pulmonary angiography (CTPA) is the
standard imaging test used for the diagnosis of a PE. It is a unique
type of X ray test which includes the injection of a contact
material into a vein providing images of the blood vessels in the
lungs. (Figure 11)
2. Radionuclide imaging (V/Q scan) is a specialized test that uses a
radioactive substance to show the parts of the lungs that are
receiving oxygen (ventilation scan) and receiving blood (perfusion
scan) in order to check if there are parts of the lungs with
differences between perfusion and ventilation. For example, if
there are clots in some of the blood vessels in the lungs, the V/Q
scan might show normal amounts of oxygen, but there will be low
blood flow to the portions of the lungs served by the clotted blood
vessels. (Figure 12)
23
 3. For pregnant women and patients for whom the use of contrast
material could be harmful, magnetic resonance imaging (MRI) test
is used. It uses radio waves and a magnetic field to provide images
of the lung. (Figure 13) (!!!)

PIC 9 PIC 9 PIC 9

Possible predisposing factors
 Predisposing factors are the factors that someone child under the
risk of developing a certain disease. It might be caused by
genetical predispositions or life events (life style, environment,…).
 In general, risk factors for PE include pregnancy, immobility, high
blood pressure, high cholesterol levels, obesity, smoking, birth
control, cancer, aging and inherited mutations of some clotting
factors genes (as discussed in the 3rd question). Three of the
above mentioned risk factors are relevant to Anna’s case.
1. She recently travelled to Turkey and felt a pain in her right calf
few days after reaching. She then felt the same pain during the
return flight. The risk factor in this case is immobility because
we usually tend to sit during the whole flight.
2. Both of Anna’s parents have had a history of DVT. This
increases the chances that she would also suffer from this
condition which might lead to a pulmonary emboli.
3. Anna is taking hormone replacement therapy drugs.

FURTHER DEVELOPMENTS

Afterwards, ventilation/perfusion (VQ) scanning is performed, which does not

help to confirm the diagnosis of the pulmonary thromboembolism.
48 hours after admission to the hospital, Anna suddenly becomes worse: the
dyspnea and pain in the chest become stronger.
Physical examination shows:
Pulse – 120 per minute, Blood pressure 110/70, increased jugular venous
pressure.
Cardiac sounds I +II + IV plus pansystolic murmur in the tricuspid area.
Respiratory rate 36 per minute
Oxygen saturation 80%
24
Interpret these results
 The dyspnea and pain in the chest become stronger
→ Dyspnea and pain are signs of PE
 Pulse – 120 per minute
→ Tachycardia, it may be result of pulmonic stenosis.
 Blood pressure 110/70
→ Readings above 90/60 and below 120/80 indicate that the
blood pressure in your arteries is Normal.

 Increased jugular venous pressure

→ The jugular venous pressure increases in patients with right
ventricular failure, pulmonic stenosis…
 Cardiac sounds I +II + IV
 Pansystolic murmur in the tricuspid area
→ Pansystolic (holosystolic) murmur: Starts with S1 and stops
at S2, without a gap between murmur and heart sounds.
 Respiratory rate 36 per minute
→ High RR (Hypoxemia)
→ And this result make me sure about PE.
 Oxygen saturation 80%
→ Low oxygen saturation level

What do you think has happened?

 Apparently, Anna had a right ventricular failure - Cor Pulmonale
 Signs of right ventricular failure: hepatomegaly, edema, JVD

Can you explain the cardiovascular findings (raised pulse, raised jugular venous
pulse, murmur in tricuspid area, heart sounds?)
 Raised pulse
→ Tachycardia, or elevated heart rate is one of the important
clinical parameters considered when diagnosing pulmonary
embolism (PE) based on Wells’ criteria. It may be result of
pulmonic stenosis.
 Raised jugular venous pulse
→ Abnormally prominent a waves of jugular venous pressure occur
in increased resistance to right atrial contraction, as in tricuspid
stenosis; also in severe 1st-, 2nd-, and 3rd-degree AV block,
supraventricular tachycardia, junctional tachycardia, pulmonary
hypertension, and pulmonic stenosis.
 Murmur in tricuspid area
25
 → Tricuspid regurgitation murmurs are often present in
patients with decompensated heart failure because of
ventricular dilatation (the initial compensatory response of
the failing heart that restores stroke volume).
 Heart sounds
→ A S4 (atrial sound or atrial gallop) occurs just before S1. It is
dull, low in pitch, and best heard at the apex with the bell.
→ Causes include pulmonary hypertension and pulmonic stenosis.
→ A S4 heart sound is often a sign of diastolic heart failure.

What management would you institute?

1. Apply continuous long-term oxygen therapy.
→ Severe hypoxemia or respiratory failure requires intubation
and mechanical ventilation.
2. Treat the underlying pulmonary disorder.
3. Use diuretic therapy cautiously because patients may be
preload-dependent.
4. Administer digoxin only if there is coexistent LV failure.

FURTHER DEVELOPMENTS

CT Pulmonary angiography (CTPA) shows massive centrally located

thrombus, blocking right pulmonary artery. (CT available)
Cardiac surgeons are discussing two options of treatment: tissue
plasminogen activator rt-PA or the surgical – pulmonary artery
embolectomy.
Anna is offered rt-PA as she her cardiovascular system is unstable.
Thrombolysis goes well and Anna slowly but surely recovers.
Heparing is replaced by warfarin after 5 days of therapy.

26
How do streptokinase and rt-PA work within the clotting cascade?
 Streptokinase is obtained from bacterial cultures. Although not itself an
enzyme, streptokinase forms a complex with endogenous plasminogen;
the plasminogen in this complex undergoes a conformational change that
allows it to rapidly convert free plasminogen into plasmin. Unlike the
forms of t-PA, streptokinase does not show selectivity for fibrin-bound
plasminogen. Urokinase is a human enzyme synthesized by the kidney
that directly converts plasminogen to active plasmin.
 Tissue plasminogen activator—t-PA is an enzyme that directly converts
plasminogen to plasmin. It has little activity unless it is bound to fibrin,
which, in theory, should make it selective for the plasminogen that has
already bound to fibrin (i.e., in a clot) and should result in less danger of
widespread production of plasmin and spontaneous bleeding. At the
pharmacologic levels of t-PA used in thrombolytic therapy, clot specificity
is lost. Alteplase is recombinant human plasminogen activator. Reteplase
is a mutated form of human t-PA with similar effects but a slightly faster
onset of action and longer duration of action. Tenecteplase is another
mutated form of t-PA with a longer half-life.

PIC 9

27
 Diagram of the fibrinolytic system. The useful thrombolytic drugs are shown
on the left. These drugs increase the formation of plasmin, the major
fibrinolytic enzyme. Antiplasmin drugs are shown on the right. Aminocaproic
acid and tranexamic acid inhibit plasmin formation.

How would you monitor the treatment of heparin and warfarin?

 The prothrombin time (PT) and the activated partial thromboplastin
time (aPTT) are laboratory tests commonly used to monitor warfarin
and heparin, respectively. These two tests depend highly on the
combination of reagent and instrument utilized.

What advice would you give her on lifestyle?

 People with genetic predisposition to clotting, such as Anna, are at higher
risks than others to develop DVT which might lead to PE. Thus Anna should
maintain a healthy lifestyle along with some changes in order to prevent the
formation of a thrombus.
→ She should avoid smoking because it damages the lining of blood
vessels which initiates the clotting cascade.
→ Obesity increases the chances of having high blood pressure and high
cholesterol levels, which may result in the formation of atherosclerotic
plaques and narrow the lumen of blood vessels resulting in the stasis
of blood, so Anna has to maintain a healthy weight along with a
healthy diet.
→ Anna should wear compression stocking which apply pressure to the
lower legs and help to maintain a normal blood flow and reduce
discomfort and swelling especially during prolonged sitting.
→ She should also avoid sitting motionless for long periods of time and
try to move around constantly.
→ Moreover, she should avoid increasing her blood pressure with dietary
changes, for example by reducing salt and sugar intake.

FURTHER DEVELOPMENTS

Anna feels fine, her INR (International Normalized Ratio) is 2.1 to 3.0.
28
She is advised to take anticoagulative therapy for no less than 6 months, maybe
even longer.

How would you look for genetic factors predisposing to thrombosis?

 The most significant breakthrough has been the confirmation of
the concept that inherited hypercoagulable conditions are present
in a large proportion of patients with venous thromboembolic
disease. These include mutations in the genes that encode
antithrombin, protein C and protein S, and the factor V Leiden and
factor II G20210 A mutations. Moreover, plasmatic risk indicators,
such as hyperhomocysteinemia and elevated concentrations of
factors II, VIII, IX, XI and fibrinogen, have also been documented.

Which items of information that you now have would influence your decision
to use a longer or shorter period of anticoagulation?
 Start warfarin once the aPTT is therapeutic and continue for 3 to 6
months. Anticoagulant to INR at 2 to 3.
→ Warfarin is long-term.
 Continue heparin until the INR has been therapeutic for 48 hours
→ Heparin is short-term.

Why does HRT predispose to thrombosis?

 The use of oxiquinolones (OCs) can affect the anticoagulant pathway
by reducing the levels of naturally occurring hemostatic agents.
These agents have been shown to increase the risk of thrombosis.

Are there any addition mechanisms contributing to an increased thrombosis

risk in pregnancy apart from oestrogen
 The three main risk factors (things that increase risk) for developing
deep vein thrombosis and pulmonary embolism are abnormal clotting,
reduced blood flow, and damage to the veins. These risks are all higher
during pregnancy, most likely because of:
→ Changes in hormone levels and blood composition that
influence clotting.
29
 → Reduced blood flow in the legs due to the weight of the
fetus pressing upon veins.
→ Injury to veins during delivery or surgery.
→ Inactivity after cesarean section surgery or delivery.

FURTHER DEVELOPMENTS

The test results for anticardiolipin antibody test and lupus anticoagulant are back.
Everything is negative.
Screening results for thrombophilia show normal protein C, S and antithrombin III.
She is heterozygous for Factor V Leiden.

What do these results mean?

 The body's natural defenses are made up of antibodies. They're
created to fight infections caused by foreign substances like
bacteria.
 People who have abnormal blood clots, repeated miscarriages, or
autoimmune diseases such as systemic lupus erythematosus (SLE)
and multiple sclerosis often have antiphospholipid antibodies.
People with cancer may also have these antibodies. The
antibodies often fade away when the cancer is treated.
 Antiphospholipid antibodies are commonly used to diagnose anti-
coagulation disorders such as lupus anticoagulant. They can also
be measured using a test known as RVVT, which measures how
long it takes for a type of viper venom to create a blood clot.
 A negative result means you don’t have these antibodies. Low to
moderate results may mean the antibodies are there because of a
recent health problem or a medicine you have taken.
 These autoantibodies can affect the body's ability to regulate
blood clotting.
 Anna doesn’t have those antibodies. Moreover, screening results
for thrombophilia show normal protein C, S and antithrombin III.
So she doesn’t have a problem in the fibrinolytic pathway.
 Anna is heterozygous for factor V Leiden (inherited disorder). This
increases the risk of developing unwanted blood clots.

30
 FURTHER DEVELOPMENTS 2

Anna develops an infection of the upper respiratory tract with couch and sore
throat two weeks after her discharge.
She starts to bring up purulent sputum 4 days after. She comes to the clinic
where the doctor diagnosis a common cold.
Some wheezing is heard while listening to her chest. She is prescribed
antibiotics - erythromycin as she is allergic to penicillin. The cough disappears
after 5 days of treatment, but Anna notices that her stool has become loose,
dark, and foul smelling. She develops nausea and upset stomach. Her friend
buys her Alka-Seltzer in the pharmacy, and she starts to take it.
The next morning Anna suddenly becomes unwell and collapses. Her husband
takes her to the local hospital, she is really ill. Examination shows pulse 92,
blood pressure 110/60. She has some bruises on her skin, mild tenderness in the
epigastriam. She asks for the bedpan and passes dark, foul smelling, loose stool.

What do you think has happened?

 Anna has a bleeding disorder in her upper gastrointestinal tract.
 Melena is characterized by a dark foul smelling stool and is a
symptom of upper gastrointestinal bleeding from the esophagus,
stomach or small intestine.
 Erythromycin increases the anticoagulant effect of warfarin, therefore
using these two drugs together increases the risks of bleeding.
 In order to prevent bleeding, PT test and/or INR should be done to
check if Anna needs a dose adjustment.
 Moreover, serious bleeding can be caused by aspirin-containing
antacid products such as Alka-Seltzer which was brought by the
friend of Anna. This has worsened Anna’s case and caused more
bleeding which resulted in a mild tenderness in the epigastrium,
bruises on her skin and dark, loose, foul smelling stool.

31
Are drug interactions with anticoagulant medication a common problem?
 Warfarin is widely used anticoagulant in treatment and prevention
of thrombosis. Despite its common use, warfarin can be
associated with bleeding complications because of its narrow
therapeutic index.

Is the Alka-Selzer significant?

 Alka-Seltzer is a combination of sodium bicarbonate, aspirin, and
anhydrous citric acid, used for the relief of heartburn, acid
indigestion and stomach aches.
 Anna is taking warfarin to prevent the formation of a thrombus,
however this drug increases the chances of bleeding. One of its
side effects include the formation of black stools which is caused
by a bleeding in the upper GI tract. That’s what happened with
Anna.
 Alka-Seltzer, an aspirin-containing antacid products, increases the
bleeding disorder that developed and caused the sensation of
being unwell and collapsed in Anna’s situation.

What physiological changes have resulted?

 Aspirin irreversibly inhibits COX-1 and the production of prostaglandins. This
results in a decrease in the cell proliferation, bicarbonate secretion and mucus
production which cause mucosal (epithelial) and endothelial damage. Since
aspirin blocks thromboxane A2, which is responsible for platelet aggregation
and vasoconstriction, blood clots are delayed, and bleeding occurs. (PIC (!!!))

PIC 9

Graph showing the physiological changes caused by aspirin

The mucosal barrier and submucosal blood vessels must be damaged for
non-variceal upper gastrointestinal bleeding to occur

32
 What tests would you do?
 After blood loss, a CBC should be done to check if Anna has lost a
significant amount of blood.
 Also, the PT test should be performed along with the INR to adjust
the dose of warfarin.

Full Blood Examination

Units Ref Range
Hemoglobin 9.9 g/l (12 - 16)
Leukocytes 10,2 х 109 / l (4,0 - 11,0)
Thrombocytes 300 х 109 / l (150-450)
Hematocrit 0,31 (0,37 - 0,47)
Neutrophils 7,9 х 109 / l (1,8 - 8,0)
Coagulation
INR 7,5 (0,8 - 1,1)
APTT 1.1 (0.85-1.15)
Fibrinogen 2,3 g / l (2,0-4,0)

Discuss the results

Units Ref Range Discussion
Hemoglobin 9.9 g/l (12 - 16) Hemoglobin levels are low
compared to the normal
range
Leukocytes 10,2 х 109 / l (4,0 - 11,0) Normal
Thrombocyte 300 х 109 / l (150-450) Normal
s
Hematocrit 0,31 (0,37 - 0,47) Anemia
Neutrophils 7,9 х 109 / l (1,8 - 8,0) Normal
Coagulation
INR 7,5 (0,8 - 1,1) It might mean Anna's
blood clots too slowly
aPTT 1.1 (0.85-1.15) Normal
Fibrinogen 2,3 g / l (2,0-4,0) Normal

How would you correct this situation?

 Since Anna lost a significant amount of blood which resulted in
anemia, she should receive a blood transfusion.
 To correct the internal normalized ratio (INR), vitamin K (1-2.5 mg)
administration is most helpful in Anna’s case (discussed in the
following question) along with reducing the dosage of warfarin.

33
 What would you administer? Give your reasons in terms of physiology.
 Vitamin K deficiency is a known factor that contributes to the
pathogenesis of coagulopathy of liver disease. It is a vital
component of the coagulation system and plays a central role in
the synthesis of various coagulation factors.
 This protein is involved in the carboxylation of glutamic acid
residue on certain vitamin K-dependent proteins to -glutamic acid.
This process is known to promote protein-membrane interaction
and hemostatic function.
 As a result of vitamin K deficiency, undercarboxylated precursors
of certain proteins are produced, which are known as PIVKAs.

FURTHER DEVELOPMENTS

Anna is given intravenous colloid and 1mg of vitamin K intravenously to counteract

the effects of warfarin.
Within 24 hours of her admission to the hospital endoscopy is done, showing acute
gastritis with multiple bleeding lesions, there are no ulcers – aspirin induced
gastritis is diagnosed.
Warfarin is stopped.

How does vitamin K work?

 Vitamin K helps to make various proteins that are needed for
blood clotting and the building of bones. Prothrombin is a vitamin
K-dependent protein directly involved with blood clotting.
Osteocalcin is another protein that requires vitamin K to produce
healthy bone tissue.

What is the effect of aspirin?

 Stimulation of platelets by thrombin, collagen, and ADP results in
activation of platelet membrane phospholipases that liberate
arachidonic acid from membrane phospholipids.
 Arachidonic acid is first converted to prostaglandin H2 by COX-1.
 Prostaglandin H2 is further metabolized to thromboxane A2,
which is released into plasma.
 Thromboxane A2 promotes the aggregation process that is
essential for the rapid formation of a hemostatic plug.
 Aspirin inhibits thromboxane A2 synthesis by acetylation of a
serine residue on the active site of COX-1, thereby irreversibly
inactivating the enzyme.

34
  This shifts the balance of chemical mediators to favor the
antiaggregatory effects of prostacyclin, thereby preventing
platelet aggregation.

FURTHER DEVELOPMENTS

After the intensive care Anna quickly recovers, bleeding is stopped.

She is told about the pharmacologic interaction between the warfarin and the
antithrombocytic effects of aspirin.

How do drugs and chemicals interact with warfarin?

 Warfarin's anticoagulant effects help prevent clot formation and
the extension of any current clots, but it has no direct impact on
clot removal or reversing ischemic tissue damage. Warfarin
exhibits its anticoagulation effects via the intrinsic and extrinsic
pathways in the clotting cascade. This activity occurs through
effects on vitamin K-dependent clotting factors (II, VII, IX, and X)
and the anticoagulant proteins C and S.
 Warfarin interferes with the activation of clotting factors by
blocking the vitamin K oxidation-reduction cycle needed for the
carboxylation of clotting factors, which ultimately lessens the
amount of active vitamin K reserves available to act as a cofactor
in the formation of glutamic acid residues within the clotting
factors mentioned above. These actions render clotting factors
inactive and unable to participate in the clotting cascade.

What is her ongoing thrombosis risk?

 There's a 40 percent chance that a patient will have a second DVT
or pulmonary embolization after 10 years following a first DVT.
 Since warfarin is stopped, Anna’s chances of developing a second
DVT are increased. However in her case, the risks of continuing
the medication outweigh its benefits.

Should other members of the family be investigated?

 Other members of the family should be advised to be
investigated; however it is not necessary. Since genetics are one
of the risk factors associated with DVT, which can progress to a PE,
screening Anna’s family would help us know if they are
predisposed to the development of DVT. If so, lifestyle changes

35
 should be implemented such as wearing compressing socks, avoid
smoking and sitting motionless for a long period of time, decrease
the intake of salt and sugar (to prevent any increase in the BP) and
maintain a healthy weight.

DIAGNOSIS

1. Pulmonary 2. Deep Venous

Embolism Thrombosis
(PE) (DVT)

CONCLUSION

REFFERENCES

36
37
1. Key information
2. Symptoms
3. What could be wrong with this lady? Your hypothesis
4. What further questions would you ask about the pain? -> Physical P.356
5. What further questions would you ask to help make the diagnosis?
6. How is the pattern and rate of onset of breathlessness important in narrowing your
hypotheses?
7. Is the calf pain important? explain
8. Do you know of any decision making tools that help doctors decide the likelihood of the
calf pain being a DVT?
9. What could happen to a clot in the leg?
10. Does this information support any of your hypotheses?
11. What new information do you have about patient?
12. What sort of examination would you do?
13. Are there risk factors for blood clots in the history?
14. What are the main findings on examination?
15. How do you interpret these examination findings? Do these findings revise your
hypotheses?
16. What is the most likely diagnosis for the chest pain now?
17. What investigations would you perform?
18. What initial treatment would you give?
19. How might a clot in the deep vein of the legs lead to a pulmonary embolus?
20. What pathological changes occur during lung infarction?
21. How often does PE occur after DVT?
22. Are there other kinds of emboli?
23. How do clots form in the body (clotting cascade)and how are they degraded (fibrinolytic
pathway)?

38
24. Fibrin (clot) Formation
25. Why do a CXR?
26. What does the CXR normally look like in PE?
27. What are the ECG changes in PE?
28. How can you interpret these laboratory findings?
29. What are the possible changes in arterial blood gases?
30. What are D dimers?
31. What are the features of a test that would help you decide whether D-Dimers a useful test
for clinically suspected DVT?
32. Why is heparin given and what is its mechanism of action?
33. Why is heparin started before warfarin? What is the mechanism of action of warfarin?
34. What other investigations would you consider?
35. Further radiological investigations to confirm diagnosis of PE:
36. Possible predisposing factors
37. Interpret these results
38. What do you think has happened?
39. Can you explain the cardiovascular findings (raised pulse, raised jugular venous pulse,
murmur in tricuspid area, heart sounds
40. What management would you institute?
41. How do streptokinase and rt-PA work within the clotting cascade?
42. How would you monitor the treatment of heparin and warfarin?
43. What advice would you give her on lifestyle?
44. How would you look for genetic factors predisposing to thrombosis?
45. Which items of information that you now have would influence your decision to use a
longer or shorter period of anticoagulation?
46. Why does HRT predispose to thrombosis?
47. Are there any addition mechanisms contributing to an increased thrombosis risk in
pregnancy apart from oestrogen
48. What do these results mean?
49. What do you think has happened?
50. Are drug interactions with anticoagulant medication a common problem?
51. Is the Alka-Selzer significant?
52. What physiological changes have resulted?
53. What tests would you do?
54. Discuss the results
55. How would you correct this situation?
56. What would you administer? Give your reasons in terms of physiology.
57. How does vitamin K work?
58. What is the effect of aspirin?
59. How do drugs and chemicals interact with warfarin?
60. What is her ongoing thrombosis risk?
61. Should other members of the family be investigated?
62. DIAGNOSIS
63. CONCLUSION
64. REFFERENCES

39
REFFERENCES
Books:

https://www.webmd.com/dvt/dvt-tests-diagnosis

https://www.mayoclinic.org/diseases-conditions/deep-vein-
thrombosis/symptoms-causes/syc-20352557
https://www.nhs.uk/conditions/hormone-replacement-therapy-hrt/
risks/
https://www.heart.org/en/health-topics/venous-thromboembolism/
understand-your-risk-for-excessive-blood-clotting

https://www.rcog.org.uk/en/patients/patient-leaflets/treatment-of-
venous-thrombosis-in-pregnancy-and-after-birth/

https://www.researchgate.net/publication/
332081109_A_lung_cancer_patient_with_deep_vein_thrombosis_A_cas
e_report_and_literature_review/figures?lo=1
https://www.google.com/url?sa=i&url=https%3A%2F
%2Fwww.drugs.com%2Fhealth-guide%2Fthromboembolism-deep-vein-
thrombosis-and-pulmonary-embolism.html&psig=AOvVaw1lF7MP1JstI-
3UiCbEjcdw&ust=1637902136792000&source=images&cd=vfe&ved=0C
AwQjhxqFwoTCPCTrI3bsvQCFQAAAAAdAAAAABAD

https://www.bionity.com/en/encyclopedia/Embolism.html
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https://www.medscape.com/answers/300901-8520/what-chest-
radiography-findings-suggest-the-presence-of-pulmonary-embolism-pe
https://pubmed.ncbi.nlm.nih.gov/11702218/

https://wa.kaiserpermanente.org/kbase/topic.jhtml?docId=ue4150

https://medlineplus.gov/lab-tests/d-dimer-test/
https://www.healthdirect.gov.au/d-dimer-test
https://www.aafp.org/afp/1999/0201/p635.html
https://www.urmc.rochester.edu/encyclopedia/content.aspx?
contenttypeid=167&contentid=antiphospholipid_antibody

https://www.healthdirect.gov.au/international-normalised-ratio-INR-
test
https://www.urmc.rochester.edu/encyclopedia/content.aspx?
contenttypeid=167&contentid=aptt
https://www.hsph.harvard.edu/nutritionsource/vitamin-k/

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ESSAY
http://mcmed.us/downloads/1622810549.pdf

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