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X
- •Acknowledgements
- •Contents at a glance
- •Contents in full
- •Abbreviations
- •Clinical clerking abbreviations
- •2.1 Agonists and antagonists: drugs acting at receptors
- •1.2 So, what is pharmacology?
- •1.3 How to use this book
- •1.4 Comment for instructors
- •1.5 Online Resource Centre
- •2.2 How receptor activation changes cells
- •2.3 Ion channels as drug targets
- •2.4 Enzymes as drug targets
- •2.5 Transporter proteins as drug targets
- •3.1 The core principles of pharmacokinetics: ADME
- •3.2 Drug elimination: clearance
- •3.3 Volume of distribution
- •3.4 Half-life of a drug
- •3.5 Absorption and bioavailability
- •4.2 Drugs used in the treatment of thromboembolic disorders
- •WORKBOOK 1
- •5.1 The physiological control of arterial blood pressure
- •5.2 Antihypertensive drugs
- •5.3 Strategies for the drug treatment of hypertension
- •WORKBOOK 2
- •6.2 Atherosclerosis
- •6.3 Preventing atherosclerosis: lipid-lowering drugs
- •6.4 Ischaemic heart disease: angina
- •6.5 Ischaemic heart disease: myocardial infarction (MI)
- •WORKBOOK 3
- •7.1 Arrhythmias
- •7.2 Anti-arrhythmic drugs
- •7.4 Chronic heart failure
- •7.5 Drugs used in heart failure
- •WORKBOOK 4
- •8.1 Structure and physiology of the skin
- •8.2 Medication for topical application to the skin
- •8.3 Eczema/dermatitis
- •8.4 Treatment of dermatitis
- •8.5 Psoriasis
- •8.6 Treatment of psoriasis
- •8.7 Acne
- •8.8 Drug treatment of acne
- •8.9 Other dermatological conditions
- •WORKBOOK 5
- •9.1 What is rheumatoid arthritis?
- •9.2 Treatment of rheumatoid arthritis
- •9.4 Disease-modifying anti-rheumatic drugs (DMARDs)
- •9.5 Cytokine blockers: biological DMARDs
- •9.6 Choice of treatment for rheumatoid arthritis
- •WORKBOOK 6
- •10.1 Allergic rhinitis
- •10.2 Treatment of allergic rhinitis
- •10.3 Urticaria
- •10.4 Treatment and management of urticaria
- •WORKBOOK 7
- •11.1 Organization of the respiratory system
- •11.2 Common airway diseases: asthma and chronic obstructive pulmonary disease (COPD)
- •11.3 Asthma
- •11.4 Treating asthma
- •11.5 Chronic obstructive pulmonary disease (COPD)
- •WORKBOOK 8
- •12.1 Structure of the gastrointestinal wall
- •12.2 The stomach
- •12.3 Disorders of the upper gastrointestinal tract
- •12.5 Nausea and vomiting
- •12.6 Antiemetic therapy
- •WORKBOOK 9
- •13.1 The lower gastrointestinal tract
- •13.2 Diarrhoea
- •13.3 Constipation
- •13.4 Irritable bowel syndrome
- •WORKBOOK 10
- •14.1 Control of blood glucose levels
- •14.2 Diabetes mellitus
- •14.3 Complications of diabetes
- •14.4 Diagnosis of diabetes
- •14.5 Drug treatment of diabetes mellitus
- •14.6 Management of diabetes
- •14.7 Obesity
- •14.8 Management of obesity
- •WORKBOOK 11
- •15.1 The thyroid gland
- •15.2 Thyroid dysfunction
- •15.3 Contraception
- •15.4 Pharmacological methods of contraception
- •WORKBOOK 12
- •16.2 The biological basis of epilepsy: brakes and accelerators
- •16.3 Three mechanisms in the drug treatment of epilepsy
- •16.4 Drugs used in the treatment of epilepsy
- •16.5 Strategy and side effects in the drug treatment of epilepsy
- •WORKBOOK 13
- •17.1 Symptoms and diagnosis of Parkinson’s disease
- •17.2 Neurodegeneration: selective death of brain neurons
- •17.3 Drug treatment of Parkinson’s disease
- •17.4 Symptoms and diagnosis of Alzheimer’s disease: a brief comment
- •17.5 Drug treatment of Alzheimer’s disease
- •WORKBOOK 14
- •18.2 Drugs in clinical use for the treatment of schizophrenia
- •18.1 What is schizophrenia? Symptoms, diagnosis, and causes
- •WORKBOOK 15
- •19.1 Depression

62 Chapter 4 Haemostasis and thromboembolic disorders
drug’s signicant side eects, which include
gastrointestinal disturbance, headache, and dizziness.
Abciximab is a preparation of an antibody fragment,
which binds to the GPIIb/IIIa receptors expressed on
platelets which have a central role in platelet recruitment,
as explained in Box 4.2. Similarly, eptifibatide and
tirofiban act as antagonists at the GPIIb/IIIa receptors.
ese drugs, administered intravenously in hospital, are
useful in the short term for certain patients undergoing
coronary angioplasty or stenting—procedures to secure
blood ow through arteries supplying the heart—and in
some cases of acute coronary syndrome.
In all cases the risk of bleeding disorders associated with
the use of antiplatelets must be weighed against the
benets.
4.2.3 Fibrinolytics (thrombolytics)
In Workbook 3, our patient Brian has a heart attack (MI).
One possibility for immediate treatment is that the patient
is ‘thrombolysed’, which means that a drug is given that
will break down the clot that has blocked an artery serving
part of his heart. is treatment will encourage the
digestion of the brin mesh of the clot, and so is called a
brinolytic or a thrombolytic. Figure 4.3 illustrates the
native brinolytic system, whereby clots are broken down
and removed. As also indicated in this gure, brinolytic
drugs promote the conversion of brin-bound
plasminogen to the proteolytic enzyme plasmin, which
digests the brin mesh of the thrombus. Streptokinase is
a bacterial protein which is administered by intravenous
infusion and directly cleaves plasminogen to plasmin.
Use of streptokinase, though, is limited because the
patient develops antibodies which appear within a few
days of administration, and which bind and inactivate the
streptokinase. Presence of antibodies, which have been
detected after prolonged periods of up to a year, can give
rise to an anaphylactoid response if the drug is readministered. For this reason streptokinase is rarely given
again after 4 days of the initial treatment.
Largely because of this limitation, the use of
streptokinase has been superseded by brinolytic drugs
which are synthetic (recombinant) versions of
endogenous tissue plasminogen activator (tPA). ese
drugs become localized to the thrombus through their
propensity to bind brin, and there cleave plasminogen
to form plasmin. ey selectively act on plasminogen
bound to brin within clots, rather than free in plasma.
Examples of these synthetic versions of tPA are
alteplase, reteplase, and tenecteplase. Alteplase has a
short half-life and so must be administered by
intravenous infusion. e longer half-lives of reteplase
and tenecteplase, however, allow their delivery by
intravenous injection, an obvious advantage to their use
in emergency situations. Unlike streptokinase, synthetic
tPAs are not antigenic and antibodies are not raised
against them. If a patient has previously received
streptokinase treatment and requires further
brinolysis, one of these drugs would be used.
Fibrinolytics play a central role in saving lives when used
immediately (as soon as possible, but at least within 12
hours) following a myocardial infarction (see also
Chapter 6). ey can unblock the aected coronary
artery, securing improved perfusion of blood and
restored oxygen delivery to the working muscle of the
heart. In addition, in some patients they have a role in
the management of DVT, and in preventing shunts and
tubes used in clinical procedures from becoming
blocked by clots.
Alteplase is also the only available treatment (other than
preventative measures such as low-dose aspirin) for
ischaemic stroke. is condition arises when a clot
reduces the ow of blood, and hence oxygen supply, to an
area of the brain, leading to the acute loss of neuronal
function in a specic locus. Ischaemic stroke can result
from a blood clot which has formed in a major artery
supplying the brain (arterial thrombosis). Alternatively,
the blood clot may have formed elsewhere (often in the
heart), and subsequently travelled as an embolus, and
become lodged in an artery in the brain (cerebral
embolism).
Alteplase must be given within 4.5 hours of the stroke to
confer benet. It must not be used where the stroke is
haemorrhagic in origin (bleeding resulting from the
bursting of a cerebral artery). Side eects of alteplase are
mainly nausea, vomiting, and bleeding; allergic reactions
and anaphylaxis are also possible.
Note that Monique in Workbook 1 does not receive
brinolytics for her deep vein thrombosis. Her treatment
involves preventing extension of the clots present and
their recurrence, but their removal is left to her body’s
natural brinolytic mechanisms. Breaking up thrombi
using brinolytic drugs has the inherent risk of producing
fragments of clots which may then lodge elsewhere,
causing further damage. is explains why these types of
drug are reserved for emergency and life-threatening
situations.

4.2 Drugs used in the treatment of thromboembolic disorders 63
4.2.4 Antifibrinolytic drugs and
haemostatics
Treatments that inhibit brinolysis will stabilize clots and
promote haemostasis and may be useful in certain
situations to prevent bleeding. Let us consider two
examples with interesting modes of action.
Tranexamic acid binds to plasminogen. As a result the
action of tPA leads to the formation of a plasmin–
tranexamate conjugate that is inactive, preventing clot
dissolution. Tranexamic acid is available for oral
administration or intravenous infusion. Its main uses are
Key references and suggested reading
Blann AD, Khoo CW. e prevention and treatment of venous
thromboembolism with LMWHs and new anticoagulants.
Vasc Health Risk Manag 2009; 5: 693–704.
Keeling D. Weighing up the risks and benets of warfarin plus
aspirin. Prescriber 2009; 20(4): 6–3.
to reduce bleeding with dental extraction and in treating
severe menorrhagia, and to reverse the eects of overdose
of streptokinase or other brinolytics.
Aprotinin is a wide-spectrum protease inhibitor with
diverse eects, including inhibition of plasmin activity
and, conversely, inhibition of components of the
coagulation cascade and thrombin activation of platelets.
Clinically, the antibrinolytic activity dominates, leading
to its use in reducing blood loss with certain major
surgical procedures, although there have been concerns
over its safety.
Osborne P, Dabin S, Rose P. A warfarin decision aid for patients
on long-term therapy. Prescriber 2009; 20(13): 13–15.

SUMMARY OF DRUGS USED FOR HAEMOSTASIS AND THROMBOEMBOLIC DISORDERS
Therapeutic class Drugs Mechanism of action Common clinical uses Comments Common adverse
Heparins Unfractionated
Heparinoid Danaparoid AT-III-mediated inhibition of factor Xa Prophylaxis of VTE in surgery
Vitamin K antagonist Warfarin Inhibits vitamin K epoxide reductase and
Direct thrombin
inhibitors
(standard) heparin
Low molecular
weight heparin
Examples:
Dalteparin
Enoxaparin
Tinzaparin
Fondaparinux AT-III-mediated selective inhibition of
Phenindione Shorter time to effect and duration
Dabigatran Direct and potent inhibitors of free and
Argatroban Anticoagulation in patients
Bivalarudin Acute coronary syndrome
Acts as cofactor for AT-III to increase its
rate of inhibition of thrombin and clotting
factors IXa-XIIa
Acts as cofactor for AT-III to increase its
rate of inhibition of clotting factors
IXa–XIIa (crucially factor Xa)
Does not inhibit thrombin
factor Xa
subsequently vitamin-K-dependent
synthesis of mature clotting factors II, VII,
IX and X, as well as anticoagulatory
proteins C and S
fibrin-bound thrombin. Reduces
coagulation and also thrombin-induced
platelet activation
VTE treatment and
prophylaxis
Acute coronary syndrome
VTE treatment and
prophylaxis
Acute coronary syndrome
VTE prophylaxis Elimination half-life of 17–21 h Haemorrhage
Anticoagulation in patients
with type II HIT
VTE treatment and
prophylaxis
Stroke prophylaxis
Many interactions
VTE prophylaxis and
treatment
Prevention of stroke in atrial
fibrillation
with type II HIT
Extremely short half-life
Extensive protein binding leads to
dose-dependent response
Overdose can be counteracted by
protamine
Longer half-life than unfractionated
heparin
Minimum protein binding leads to
predictable dose response profile
Approximately 2 days required for
effect
Metabolized by hepatic microsomal
P450 enzymes leading to many
interactions
Long half-life of 36–40 h
but used rarely because of side
effects
Taken orally
Substitute for warfarin
Elimination half-life of 12–14 h
INR monitoring not required
Very short half-life <1 hour—
administered as intravenous infusion
Very short half-life <30 min:
administered as intravenous infusion
Used in combination with both
clopidogrel and aspirin
drug reactions
Haemorrhage
Thrombocytopenia
Bruising and pain at
injection site
Osteoporosis
Haemorrhage
Thrombocytopenia
Bruising and pain at
injection site
Anaemia
Thrombocytopenia
Haemorrhage
Bruising and pain at
injection site
Hypersensitivity reactions
Haemorrhage
Skin necrosis
Hepatic dysfunction
Liver and kidney damage
Rash
Myocarditis
Blood dyscrasia
Haemorrhage
Anaemia
Bruising
Nausea and GI
disturbance
Haemorrhage
Nausea
Purpura
Haemorrhage
Hypersensitivity reactions
64 Chapter 4 Haemostasis and thromboembolic disorders

Direct factor Xa
inhibitors (i.e. not
AT-III-mediated)
Oral antiplatelets Aspirin Irreversible inhibition of COX
Rivaroxaban
Apixaban
Clopidogrel
Prasugrel
Highly selective, reversible inhibition of
factor Xa
Low dose selectively reduces platelet
thromboxane production
Pro-drugs
Active metabolite irreversibly inhibits
ADP binding to platelet P2Y12 receptor to
reduce platelet aggregation
VTE prophylaxis and
treatment
Stroke prevention in atrial
fibrillation
Secondary prevention of
thrombotic arterial events in
cardiovascular,
cerebrovascular, and
peripheral arterial disease
Treatment of acute coronary
syndrome and acute
ischaemic stroke
Prevention of
atherothrombotic events in
acute coronary syndrome
(in combination with aspirin)
Taken orally
Substitute for warfarin
Good bioavailability
INR monitoring not required
Elimination half-life of 7–11 h for
rivaroxaban; ~12 h for apixaban
Low dose required for antiplatelet
effect (higher dose as analgesic)
Half-life short (~20 min) but effect
very long-lasting (days)
Used in combination with other
antiplatelets, e.g. clopidogrel,
prasugrel, dipyridamole
Long-lasting antiplatelet effect
because of irreversible binding
4.2 Drugs used in the treatment of thromboembolic disorders 65
Haemorrhage
Nausea and GI
disturbance
Anaemia
Bruising
Gastrointestinal bleeding/
disturbance
Bronchospasm
Haemorrhage
Haemorrhage
GI bleeding/disturbance
Rash
Anaemia
Haematoma
Epistaxis
(nosebleeds)
Glycoprotein IIb/IIIa
receptor inhibitors
Ticagrelor Non-competitive antagonist at platelet
Dipyridamole Phosphodiesterase inhibitor
Abciximab
Tirofiban
Eptifibatide
P2Y12 receptor
Reduces ADP-mediated platelet
aggregation
Raises cyclic AMP levels in platelets and
inhibits aggregation
Block glycoprotein IIb/IIIa receptor
Prevent fibrinogen binding to reduce
platelet aggregation
Acute coronary syndrome
(used in combination with
low-dose aspirin)
Secondary prevention of
ischaemic cerebrovascular
events (in combination with
aspirin)
Prevention of
thromboembolism with
mechanical heart valves
(in combination with oral
anticoagulant)
Acute coronary syndrome
Percutaneous coronary
intervention
Half-life of active metabolite is ~8 h
(Grapefruit juice enhances antiplatelet
effect)
Administered intravenously (specialist
use only)
Used in combination with heparin and
aspirin
Abciximab used only once due to
generation of antibodies
Dyspnoea
Haemorrhage
Dermal bleeding
Bruising
GI disturbance
Headache
Tachycardia
Haemorrhage
Thrombocytopenia
Allergic reactions
Nausea

Therapeutic class Drugs Mechanism of action Common clinical uses Comments Common adverse
drug reactions
Fibrinolytics
(Thrombolytics)
Antifibrinolytics Tranexamic acid Binds to plasminogen and prevents
ADP, adenosine diphosphate; AT-III, antithrombin-III; COX, cyclo-oxygenase; GI, gastrointestinal; HIT, heparin-induced thrombocytopenia; INR, international normalized ratio; tPA, tissue plasminogen activator;
VTE, venous thromboembolism
Non-synthetic:
Streptokinase
Urokinase
Synthetic
recombinant tPAs
Alteplase
Reteplase
Tenecteplase
Aprotinin Inhibits proteases including plasmin Prevention of perioperative
Cleave plasminogen to generate plasmin
which digests clot
(Synthetic drugs are more selective for
fibrin-bound plasminogen; ‘clotselective’)
activation by tPA, reducing fibrinolysis
Acute myocardial infarction
(Survival rate increases if
drug given within 1 h of
symptoms)
Ischaemic stroke
Pulmonary embolism
Prevention or treatment of
haemorrhage associated
with excessive fibrinolysis,
e.g. menorrhagia, dental
extraction
haemorrhage
Short half-life: administered by
intravenous infusion
Antibodies to streptokinase produced
(not used after 4 days of initial
treatment and not given on a second
occasion)
Reteplase and tenecteplase have
longer half-lives so can be given by
intravenous injection enabling faster
delivery to patient
Intravenous or oral administration Nausea and vomiting
Elimination half-life of 10 h Anaphylaxis
Haemorrhage
Nausea and vomiting
Hypotension
Allergic reactions
Diarrhoea
Myocardial infarction
Acute renal failure
GI disturbance
66 Chapter 4 Haemostasis and thromboembolic disorders

WORKBOOK 1
Thromboembolic disorders
Introducing Monique, a patient with deep vein thrombosis
The patient: a simplified case history
On Sunday morning Monique woke with a headache. As she crawled out of bed to get a glass
of water and some paracetamol, she also found she had a sharp pain in her right leg. The
headache was probably due to the wine that she and her closest friend, Sunita, had drunk the
night before, while Monique told her all about her recent travels in Australia. But she could not
explain the distressing pain in her leg.
When Monique described the pain to her, Sunita (a final-year pharmacy student) convinced her
that they should go to Accident and Emergency (A&E) at the local University Hospital. On the
way Monique became more and more breathless, and then, when coughing, noticed blood;
Sunita had to pull over and call an ambulance.
Monique is seen immediately by the hospital doctor. While examining her he asks detailed
questions which are relevant to her symptoms.
A table of clinical clerking abbreviations is given on page xviii.
CLINICAL CLERKING FOR MONIQUE RICHARDS AT A&E
DEPARTMENT
PC: Pain in leg and chest, shortness of breath, sweating, light-headedness, haemoptysis
Haemoptysis: Monique is coughing up blood.
HPC: Pain in leg spreading to chest, worse on exertion; shortness of breath progressing
PMH: Nil significant
Monique has suffered from no major or significant medical conditions in the past.
SH: Secretary who sits at a small desk all day. Recently returned from Australia on a 26-hour flight.
Drinks about 40 UK units of alcohol at irregular intervals every week. (One unit (UK) is 8 g or 10 ml of
pure alcohol.)
Altered blood flow resulting from sitting in a cramped position for long periods can increase the risk
of deep vein thrombosis (DVT).
High alcohol intake can influence the hepatic cytochrome P450 enzymes responsible for
metabolizing the oral anticoagulant warfarin. Irregular alcohol intake can make this effect erratic.

68 Chapter 4 Haemostasis and thromboembolic disorders
This will need to be considered if Monique is prescribed warfarin later. She should be told the
maximum recommended units of alcohol per week, and the consequences of exceeding this limit.
DH: Combined hormonal contraceptive pill
Some hormonal contraceptives increase the risk of thromboembolism by altering the coagulability
of the blood (see Chapter 15). The risk is greater where additional factors exist, such as smoking or
being overweight as is the case for Monique.
O/E:
1) Pulse = 120/min (normal 60/min)
Monique’s pulse is very elevated.
2) Dyspnoea, tachypnoea and oxygen saturation
Dyspnoea: shortness of breath.
Tachypnoea: rapid breathing.
oxygen saturation.
Monique is finding it difficult to breathe, which could be due to a blockage in her lungs or a heart
attack.
3) Calf circumference: right leg = 40 cm, left leg = 37 cm
Note the difference of 3 cm between left and right legs. A difference of >3 cm is one of the
indicators in the Wells score used to diagnose DVT.
4) Blood pressure = 90/50 mmHg (ideal, 120/80 mmHg)
Monique’s blood pressure is below normal and a cause for concern (more about blood pressure in the
next case study).
5) Cyanosis
Monique’s lips and fingers are blue.
6) Weight = 90 kg
Monique is overweight; this increases her risk of DVT, heart problems, and diabetes.
Biochemistry:
International normalized ratio (INR) = 1.1
The INR is the ratio of the time taken to form a clot in a sample of the patient’s blood following
addition of tissue factor (prothrombin time) compared with a standardized reference sample. It is
used to monitor the effect of oral anticoagulants. Normally, people have an INR between 0.8 and 1.2.
Patients receiving treatment for VTE have higher INRs; anticoagulant medication increases the
prothrombin time (their blood takes longer to clot). The target INR value varies with risk of
thrombosis. The current target for anticoagulant treatment of venous thromboembolism (VTE) for
a patient like Monique is 2.5.

WORKBOOK 1 Thromboembolic disorders 69
Investigations:
1) DVT risk score
Most guidelines calculate a DVT risk by taking the following clinical features (DVT risks/
symptoms) into consideration:
• activecancer(treatmentongoing,within6months,orpalliative)
• paralysis,paresis,orrecentplasterimmobilizationofthelowerextremities
• recentlybedriddenfor3daysormore,ormajorsurgerywithin12weeksrequiringgeneralor
regional anaesthesia
• localizedtendernessalongthedistributionofthedeepvenoussystem
• entirelegswollen
• calfswellingatleast3cmlargerthanasymptomaticside
• pittingoedemaconnedtothesymptomaticleg
• collateralsupercialveins(non-varicose)
• previouslydocumentedDVT.
2) Leg vein ultrasound (Doppler scan) for DVT
In the presence of a likely DVT score, a leg vein ultrasound is usually offered.
The Doppler scan is commonly used to diagnose vascular disease and the presence of thrombi in
veins, and provides information about blood flow.
3) Assessment for symptoms of pulmonary embolism
Clot fragments from a DVT can break away and travel to the lung, causing blockage to a blood
vessel, called a pulmonary embolism (PE). Patients diagnosed with DVT are generally assessed
for symptoms of PE, and most guidelines recommend calculation of a PE score. This is done by
taking the following clinical features (PE risks/symptoms) into consideration:
• clinicalsignsandsymptomsofDVT(minimumoflegswellingandpainwithpalpationofthe
deep veins)
• heartrate> 100 beats/min
• immobilizationformorethan3days,orsurgeryintheprevious4weeks
• previousDVT/PE
• haemoptysis
• malignancy(treatmentongoing,within6months,orpalliative)

70 Chapter 4 Haemostasis and thromboembolic disorders
4) Computed tomography pulmonary angiography (CTPA)
Patients with a likely PE score should either have a CTPA immediately, or start parenteral
anticoagulation followed by a CTPA.
CTPA is non-invasive imaging of the lungs. It is the gold standard for diagnosis of PE. It also offers
the possibility of detecting other lung disorders.
5) D-dimers: elevated
D-dimers are fragments of cross-linked fibrin formed as plasmin degrades clots (see Figure 4.3).
Levels become elevated following thrombus formation. Testing is usually reserved for when the
suspicion of PE is low to moderate. In Monique’s case it was high, and D-dimer levels were therefore
not measured.
Diagnosis: DVT; multiple PE with haemodynamic instability
Plan:
Oxygen
Analgesia
Commence unfractionated heparin infusion
Commence warfarin as per rapid initiation protocol
Note: Thrombosis is a major cause of death and disability. It is divided into:
1) arterial block
• mainlycausedbydamagetotheendotheliallayerofbloodvessels(e.g.byatherosclerosis)
• largeplateletcomponent;thereforeaspirinismosteffectiveforpreventionandtreatment
• leadstomyocardialinfarction,stroke,andperipheralischaemia
2) venous block
• mainlycausedbystasis,i.e.poolednon-owingblood
• largebrincomponentandasmallerplateletcomponent;thereforeanticoagulantsaremost
effective for prevention and treatment
• leadstoDVTandpulmonaryembolism(venousthromboembolism,VTE)
Dr Carter Brown tells Monique, who can barely breathe, that she has a clot (thrombus) as a
result of thrombosis in a vein in her right leg (DVT), as well as several in her lung (multiple PEs).
He prescribes intravenous heparin.
The nurse sets up the heparin infusion using a vein on Monique’s hand.

WORKBOOK 1 Thromboembolic disorders 71
EXPLORING MONIQUE’S CONDITION
1a) What is haemostasis?
1b) What is this process called thrombosis that occurred in the vein in Monique’s right leg?
Dr Brown explains that unfortunately Monique’s DVT has led to pulmonary embolism (PE).
2) What is PE? How has Monique’s DVT led to PE?
Sunita asks Dr Brown if emboli can travel to other parts of the body. He says that they can, and
asks her to imagine that Monique has an embolus that travels in her blood into the arteries
supplying her heart, brain, or lungs. There are several life-threatening conditions that result from
the blockage of these arteries with emboli.
3) List at least two of these life-threatening conditions. Explain what they are.
Dr Carter Brown explains to Monique that the factors contributing to venous thrombosis fall into
four main groups:
a) pooledstaticblood(stasis),causedforexamplebyimmobilizationoflegsorvenous
obstruction
b) pregnancy
c) abnormality of clotting proteins, e.g. malignancy, or as a result of taking oral contraceptives
d) abnormality of surface in contact with blood, e.g. in fractures or mechanical heart valves.
4a) Which of these factors probably contributed to Monique’s DVT?
Refer back to the A&E investigations and clerking.
4b) List three factors that could cause thromboembolism as a result of abnormality of the surface in
contact with blood (see Table 4.2).
Monique asks Dr Brown how the swelling suddenly appeared in her leg. Before he can explain,
Sunita, to impress him, starts talking about coagulation.
She says the swelling in Monique’s right leg (DVT) was caused by inappropriate coagulation in
the affected vein. She explains how the different drugs on Monique’s prescription chart target
different elements of what she and Dr Brown refer to as ‘thrombus formation’.
5) What are the two main elements of thrombus formation that are targeted by antithrombotic drugs?
6a) What is coagulation?
6b) What are the two clotting cascades called? (Give traditional names as well as more recent
descriptive names.)
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